Compounds > vericiguat
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vericiguat

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Description

vericiguat: a guanylate cyclase stimulator; FDA approved for the treatment of chronic heart failure. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

vericiguat : A pyrazolopyridine that is 5-fluoro-1H-pyrazolo[3,4-b]pyridine in which the amino hydrogen at position 1 has been substituted by a 2-fluorobenzyl group and the hydrogen at position 3 has been substituted by a 4,6-diamino-5-[(methoxycarbonyl)amino]pyrimidin-2-yl group. It is a soluble guanylate cyclase stimulator which is used for treatment of chronic heart failure. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID54674461
CHEMBL ID4066936
CHEBI ID142432
SCHEMBL ID429958
MeSH IDM000613267

Synonyms (53)

Synonym
mk-1242
bay-1021189
bay1021189
1350653-20-1
vericiguatum
methyl n-[4,6-diamino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate
vericiguat
CHEBI:142432 ,
methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate
S9693
vericiguat [who-dd]
vericiguat [orange book]
vericiguat [jan]
SCHEMBL429958
methyl (4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo(3,4-b)pyridin-3-yl)pyrimidin-5-yl)carbamate
vericiguat [inn]
unii-lv66adm269
vericiguat [usan]
bay 1021189
vericiguat [usan:inn]
methyl (4,6-diamino-2-(5-fluoro-1-((2-fluorophenyl)methyl)-1h-pyrazolo(3,4-b)pyridin-3-yl(pyrimidin-5-yl)carbamate
lv66adm269 ,
verquvo
who 9805
methyl n-(4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo(3,4-b)pyridin-3-yl)pyrimidin-5-yl)carbamate
methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate
QZFHIXARHDBPBY-UHFFFAOYSA-N
AKOS025289795
mfcd28502029
methyl (4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)carbamate
vericiguat (jan/usan/inn)
D11051
HY-16774
CS-6981
BCP18886
bay1021189; bay 1021189; bay-1021189; bay10-21189; bay-10-21189; bay 10-21189
bay1021189; verquvo
DB15456
gtpl10010
SB16806
CHEMBL4066936
Q27283201
A887763
P14957
MS-27517
EX-A4694
bay1021189bay1021189
AC-36737
DTXSID001318361
methyl 4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-ylcarbamate
methyl n-(4,6-diamino-2-{5-fluoro-1-[(2-fluorophenyl)methyl]-1h-pyrazolo[3,4-b]pyridin-3-yl}pyrimidin-5-yl)carbamate
methyl n-(4,6-diamino-2-(5-fluoro-1-((2-fluorophenyl)methyl)pyrazolo(3,4-b)pyridin-3-yl)pyrimidin-5-yl)carbamate
methyl (4,6-diamino-2-(5-fluoro-1-((2-fluorophenyl)methyl)-1h-pyrazolo(3,4-b)pyridin-3-yl)pyrimidin-5-yl)carbamate

Research Excerpts

Overview

Vericiguat is a soluble guanylate cyclase stimulator. It is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization in adults with symptomatic chronic HF.

ExcerptReferenceRelevance
"Vericiguat is a soluble guanylate cyclase stimulator indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization in adults with symptomatic chronic HF and ejection fraction less than 45%. "( Vericiguat in Combination with Short-Acting Nitroglycerin in Patients With Chronic Coronary Syndromes: The Randomized, Phase Ib, VENICE Study.
Becker, C; Besche, N; Boettcher, M; Donath, F; Düngen, HD; Gurniak, M; Karakas, M; Koch, T; Mikus, G; Thuermann, PA; Werner, N, 2022)		3.61
"Vericiguat is a novel agent which has been shown to reduce the HF hospitalisation risk in patients with a recent WHF event."( Should vericiguat be initiated in geriatric inpatients with heart failure with reduced ejection fraction and a worsening heart failure event prior to discharge?
Hellemans, L; Hias, J; Tournoy, J; Van Aelst, L; Van der Linden, LR; Vandenbriele, C; Walgraeve, K, 2023)		2.09
"Vericiguat is a soluble guanylate cyclase stimulator. "( Pharmacokinetics and mass balance of vericiguat in rats and dogs and distribution in rats.
Bütehorn, U; Gerisch, M; Hucke, F; Janssen, W; Kern, A; Lang, D; Sandmann, S; Schwarz, T; Steinke, W, 2022)		2.44
"Vericiguat is a soluble guanylate cyclase stimulator approved by multiple global regulatory bodies and recommended in recently updated clinical practice guidelines to reduce morbidity and mortality in patients with worsening chronic heart failure (HF) with reduced ejection fraction (HFrEF). "( Practical Patient Care Considerations With Use of Vericiguat After Worsening Heart Failure Events.
Bauersachs, J; Diez, J; Gustafsson, F; Jankowska, EA; Mentz, RJ; Rao, VN; Senni, M, 2023)		2.61
"Vericiguat is a novel, orally used, small molecule, and direct stimulator of the soluble guanylate cyclase, and thus, it enhances the production of cyclic guanosine monophosphate."( Vericiguat: A New Hope for Heart Failure Patients.
Al-Horani, RA; Chiles, R, 2022)		2.89
"Vericiguat is a novel oral soluble guanylate cyclase (sGC) stimulator which was approved by the US Food and Drug administration (FDA) in January 2021 for use in patients with symptomatic chronic HF and an ejection fraction less than 45% following a hospitalization for HF or the need for outpatient intravenous diuretics."( Vericiguat for the treatment of heart failure with reduced ejection fraction.
Butler, J; Fudim, M; Greene, SJ; Khan, MS; Mentz, RJ; Siddiqi, AK, 2023)		3.07
"Vericiguat is a once-daily oral stimulator of sGC that restores this system."( Identifying the patient with heart failure to be treated with vericiguat.
Bonilla Palomas, JL; Escobar Cervantes, C; Esteban Fernández, A; González Costello, J; González Franco, Á; Mirabet, S; Núñez Villota, J; Recio Mayoral, A; Rubio Gracia, J, 2023)		1.87
"Vericiguat is a soluble guanylate cyclase stimulator indicated to reduce the risk of cardiovascular death and hospitalization due to heart failure. "( Assessing QTc Effects of Vericiguat Using Two Different Concentration-QTc Modeling Approaches.
Becker, C; Frei, M; Garmann, D; Meyer, M; Ruehs, H; Solms, A; Trujillo, ME, 2023)		2.66
"Vericiguat is a new soluble guanylate cyclase (sGC) activator with cardioprotective properties."( Vericiguat alleviates ventricular remodeling and arrhythmias in mouse models of myocardial infarction via CaMKII signaling.
Chen, T; Gong, Y; Huang, H; Kong, B; Shuai, W; Zhang, J, 2023)		3.07
"Vericiguat is a stimulator of soluble guanylate cyclase currently under investigation as a first-in-class therapy for worsening chronic heart failure (NCT02861534). "( Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies.
Becker, C; Besche, N; Boettcher, M; Gerisch, M; Gerrits, M; Lemmen, J; Lobmeyer, M; Mueck, W; Radtke, M; Thomas, D, 2020)		2.24
"Vericiguat acts as a sGC stimulator thus targeting the NO-sGC-cGMP pathway by a different mechanism that complements the current pharmacotherapy for HF."( Vericiguat for the treatment of heart failure: mechanism of action and pharmacological properties compared with other emerging therapeutic options.
De Groote, P; Donal, E; Galinier, M; Hulot, JS; Juillière, Y; Logeart, D; Trochu, JN, 2021)		2.79
"Vericiguat is an oral soluble guanylate cyclase stimulator that enhances the cyclic guanosine monophosphate (GMP) pathway."( Vericiguat, organic nitrates, and heart failure in African Americans.
Guglin, M; Ilonze, OJ, 2021)		2.79
"Vericiguat is a novel soluble guanylate cyclase stimulator that is safe and effective for reducing the risk of cardiovascular death and HF hospitalization in adults with symptomatic chronic HF and reduced EF."( Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the Treatment of Heart Failure.
Campbell, N; Frey, K; Kalabalik-Hoganson, J, 2022)		3.61

Effects

Vericiguat has been shown to directly stimulate sGC and enhance sGC sensitivity to endogenous NO. It has shown an additional statistical add-on therapy efficacy by reducing morbi-mortality in patients with WCHF.

ExcerptReferenceRelevance
"Vericiguat has a dual mode of action on this axis, it both sensitizes sGC to low levels of NO, and can directly stimulate sGC in the absence of any endogenous NO. VICTORIA was a Phase 3 trial that compared vericiguat, at a target dose of 10 mg, with placebo in 5050 patients with HFrEF (ejection fraction < 45%) on top of guideline-indicated therapy."( Drug Treatment of Heart Failure with Reduced Ejection Fraction: Defining the Role of Vericiguat.
Coats, AJS; Tolppanen, H, 2021)		1.57
"Vericiguat has shown an additional statistical add-on therapy efficacy by reducing morbi-mortality in patients with WCHF."( Vericiguat for the treatment of heart failure: mechanism of action and pharmacological properties compared with other emerging therapeutic options.
De Groote, P; Donal, E; Galinier, M; Hulot, JS; Juillière, Y; Logeart, D; Trochu, JN, 2021)		2.79
"Vericiguat has been shown to directly stimulate sGC and enhance sGC sensitivity to endogenous NO."( A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of the Oral Soluble Guanylate Cyclase Stimulator: The VICTORIA Trial.
Anstrom, KJ; Armstrong, PW; Butler, J; Ezekowitz, J; Hernandez, AF; Koglin, J; Lam, CSP; O'Connor, CM; Patel, MJ; Pieske, B; Ponikowski, P; Roessig, L; Temple, T; Voors, AA, 2018)		1.2

Treatment

Vericiguat treatment for 12 weeks was associated with reductions in hsCRP and SUA. Treatment is considered when the individual patient experiences decompensation despite being on guideline-recommended medication.

ExcerptReferenceRelevance
"Vericiguat treatment may benefit to treat heart failure."( The efficacy of vericiguat for heart failure: A meta-analysis of randomized controlled trials.
Li, F; Ma, G; Pan, Y; Qu, C, 2023)		2.7
"Vericiguat treatment for 12 weeks was associated with reductions in hsCRP and SUA, and a higher likelihood of achieving an hsCRP value of ≤3.0 mg/L and SUA value of <7.0 mg/dL."( Evaluation of high-sensitivity C-reactive protein and uric acid in vericiguat-treated patients with heart failure with reduced ejection fraction.
Butler, J; Igl, BW; Kramer, F; Lam, CSP; Maggioni, AP; Pieske, B; Roessig, L; Shah, SJ; Voss, S, 2020)		2.24
"Treatment with vericiguat is considered when the individual patient experiences decompensation despite being on guideline-recommended medication, e.g., angiotensin-converting inhibitor/AT1 receptor antagonist, beta-adrenoceptor antagonist, spironolactone, and sodium-glucose transporter 2 inhibitors."( A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure.
Grimm, D; Sahana, U; Schulz, H; Simonsen, U; Wehland, M, 2023)		1.52

Toxicity

Concomitant use of sacubitril/valsartan for at least 3 months did not alter the efficacy of vericiguat and was similarly safe and tolerated in both study arms. There was no significant differences between the groups in terms of cardiovascular death and HF hospitalization.

ExcerptReferenceRelevance
" Available phase IIb data in HFrEF patients indicate vericiguat is safe and well-tolerated, and exploratory analyses indicate that it results in a dose-dependent, clinically significant reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at the highest tested dose."( A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of the Oral Soluble Guanylate Cyclase Stimulator: The VICTORIA Trial.
Anstrom, KJ; Armstrong, PW; Butler, J; Ezekowitz, J; Hernandez, AF; Koglin, J; Lam, CSP; O'Connor, CM; Patel, MJ; Pieske, B; Ponikowski, P; Roessig, L; Temple, T; Voors, AA, 2018)		0.73
" Eligible RCTs were included that reported mortality, the change of EuroQol Group 5-Dmensional Self-report Questionnaire (EQ-5D) US index, N-terminal pro-B-type natriuretic peptide (NT-proBNP), or serious adverse events (SAEs)."( The efficacy and safety of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis.
Huang, J; Xiong, B; Zheng, W; Zheng, X, 2018)		0.48
" There were no deaths or serious adverse events."( Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.
Arens, E; Becker, C; Boettcher, M; Loewen, S; Mueck, W; Thomas, D; Yoshikawa, K, 2021)		0.86
"Concomitant use of sacubitril/valsartan for at least 3 months did not alter the efficacy of vericiguat and was similarly safe and tolerated in both study arms."( Efficacy and safety of vericiguat in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan: insights from the VICTORIA trial.
Alemayehu, WG; Armstrong, PW; Butler, J; Edelmann, F; Ezekowitz, J; Hernandez, AF; Lam, CSP; McMullan, C; O'Connor, CM; Pieske, B; Ponikowski, P; Roessig, L; Senni, M; Sim, D; Voors, AA; Westerhout, CM, 2022)		1.25
"8%) in the placebo group reported one or more treatment-emergent adverse events, all of mild or moderate intensity."( Evaluation of the Influence of Sildenafil on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults.
Becker, C; Boettcher, M; Krausche, R; Nowotny, B, 2023)		1.12
" This study investigated whether sildenafil was safe to use in individuals treated with vericiguat."( Evaluation of the Influence of Sildenafil on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults.
Becker, C; Boettcher, M; Krausche, R; Nowotny, B, 2023)		1.34
" There was no significant difference in adverse effects between the vericiguat group and placebo group, and no significant differences between the groups in terms of cardiovascular death and HF hospitalization."( Efficacy and safety of vericiguat in heart failure: a meta-analysis.
Guo, S; Jiang, H; Li, B; Ma, J, 2023)		1.46

Pharmacokinetics

Vericiguat was tested in patients with heart failure and left ventricular ejection fraction < 45% in the SOCRATES-REDUCED study (NCT01951625) A low pharmacokinetic interaction potential was estimated from in vitro data and confirmed in vivo.

ExcerptReferenceRelevance
" Hence, understanding the clearance mechanisms, elimination, and potential for pharmacokinetic drug-drug interactions of vericiguat is important for dose recommendations in this patient population."( Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies.
Becker, C; Besche, N; Boettcher, M; Gerisch, M; Gerrits, M; Lemmen, J; Lobmeyer, M; Mueck, W; Radtke, M; Thomas, D, 2020)		1
"A low pharmacokinetic interaction potential of vericiguat was estimated from in vitro data and confirmed in vivo."( Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies.
Becker, C; Besche, N; Boettcher, M; Gerisch, M; Gerrits, M; Lemmen, J; Lobmeyer, M; Mueck, W; Radtke, M; Thomas, D, 2020)		1.05
"Safety, pharmacodynamic (PD), and pharmacokinetic (PK) interactions between vericiguat and drugs used in HF (sacubitril/valsartan [SV] and aspirin [acetylsalicylic acid]) or with a narrow therapeutic index (warfarin) were evaluated in three phase I studies."( Pharmacodynamic and Pharmacokinetic Interaction Profile of Vericiguat: Results from Three Randomized Phase I Studies in Healthy Volunteers.
Becker, C; Boettcher, M; Gerrits, M; Loewen, S, 2021)		1.09
"5 h [fasted]) with a mean half-life of about 22."( Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.
Arens, E; Becker, C; Boettcher, M; Loewen, S; Mueck, W; Thomas, D; Yoshikawa, K, 2021)		0.86
"The objective of this article was to characterize the pharmacokinetics and pharmacokinetic variability of vericiguat combined with guideline-directed medical therapy (standard of care), and identify exposure-response relationships for safety (hemodynamics) and pharmacodynamic markers of efficacy (N-terminal pro-B-type natriuretic peptide concentration [NT-proBNP]) in patients with heart failure and left ventricular ejection fraction < 45% in the SOCRATES-REDUCED study (NCT01951625)."( Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.
Austin, R; Becker, C; Frei, M; Garmann, D; Grevel, J; Klein, D; Meyer, M; Pieske, B; Roessig, L; Ruehs, H, 2021)		1.09
" Pharmacokinetic (PK) data from the phase II trial SOCRATES-REDUCED (Soluble Guanylate Cyclase Stimulator in Heart Failure Study) and the phase III trial VICTORIA (Vericiguat Global Study in Patients With Heart Failure With Reduced Ejection Fraction) were used to characterize vericiguat PK."( Population Pharmacokinetics of Vericiguat in Patients With Heart Failure With Reduced Ejection Fraction: An Integrated Analysis.
Armstrong, PW; Arrington, L; Becker, C; Blaustein, RO; Gheyas, F; Meyer, M; Passarell, J; Patel, Y; Trujillo, ME; Wenning, L, 2022)		1.2
" Safety, hemodynamic changes, and pharmacokinetic effects were assessed."( Evaluation of the Influence of Sildenafil on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults.
Becker, C; Boettcher, M; Krausche, R; Nowotny, B, 2023)		1.12

Compound-Compound Interactions

Vericiguat was co-administered orally with omeprazole, magnesium/aluminum hydroxide, ketoconazole, rifampicin, mefenamic acid, midazolam, warfarin, digoxin, sacubitril/valsartan, aspirin, or sildenafil.

ExcerptReferenceRelevance
" Hence, understanding the clearance mechanisms, elimination, and potential for pharmacokinetic drug-drug interactions of vericiguat is important for dose recommendations in this patient population."( Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies.
Becker, C; Besche, N; Boettcher, M; Gerisch, M; Gerrits, M; Lemmen, J; Lobmeyer, M; Mueck, W; Radtke, M; Thomas, D, 2020)		1
" This was complemented by a human mass balance study and ten drug-drug interaction studies in healthy volunteers wherein vericiguat was co-administered orally with omeprazole, magnesium/aluminum hydroxide, ketoconazole, rifampicin, mefenamic acid, midazolam, warfarin, digoxin, sacubitril/valsartan, aspirin, or sildenafil."( Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies.
Becker, C; Besche, N; Boettcher, M; Gerisch, M; Gerrits, M; Lemmen, J; Lobmeyer, M; Mueck, W; Radtke, M; Thomas, D, 2020)		1
" These observations were supported by phase I drug-drug interaction studies."( Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies.
Becker, C; Besche, N; Boettcher, M; Gerisch, M; Gerrits, M; Lemmen, J; Lobmeyer, M; Mueck, W; Radtke, M; Thomas, D, 2020)		0.8

Bioavailability

0 mg IR tablets with food increased bioavailability by 19% (estimated ratio 119% [90% confidence interval]: 108; 131), reduced PK variability, and prolonged vericiguat absorption relative to the fasted state.

ExcerptReferenceRelevance
" Bioavailability and food effects on vericiguat PK (IR tablets) were also studied in European subjects."( Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.
Arens, E; Becker, C; Boettcher, M; Loewen, S; Mueck, W; Thomas, D; Yoshikawa, K, 2021)		1.13
"0 mg IR tablets with food increased bioavailability by 19% (estimated ratio 119% [90% confidence interval]: 108; 131]), reduced PK variability, and prolonged vericiguat absorption relative to the fasted state."( Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.
Arens, E; Becker, C; Boettcher, M; Loewen, S; Mueck, W; Thomas, D; Yoshikawa, K, 2021)		1.06
"Vericiguat pharmacokinetics were well described by a one-compartment model with apparent clearance, apparent volume of distribution, and absorption rate constant."( Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.
Austin, R; Becker, C; Frei, M; Garmann, D; Grevel, J; Klein, D; Meyer, M; Pieske, B; Roessig, L; Ruehs, H, 2021)		2.31
" Impaired NO-sGC-cGMP signaling in HF is secondary to reduced NO bioavailability and altered redox state of sGC, which becomes less responsive to NO."( Vericiguat for Heart Failure with Reduced Ejection Fraction.
Aimo, A; Carubelli, V; Cimino, G; Dell'Aquila, A; Emdin, M; Inciardi, R; Lombardi, CM; Nodari, S; Pagnesi, M; Ravera, A; Tomasoni, D; Vizzardi, E, 2021)		2.06

Dosage Studied

Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF. The distribution of steady-state doses in VICTORIA was similar across CL/F quartiles, suggesting that the ability to reach and maintain dosing at the target 10-mg dose was not related to vericguat exposure.

ExcerptRelevanceReference
" The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point."( Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial.
Butler, J; Filippatos, G; Gheorghiade, M; Greene, SJ; Kraigher-Krainer, E; Lam, CS; Maggioni, AP; Müller, K; Pieske, B; Ponikowski, P; Roessig, L; Samano, ET; Shah, SJ; Solomon, SD, 2015)		1.05
" The exploratory secondary analysis suggested a dose-response relationship whereby higher vericiguat doses were associated with greater reductions in NT-proBNP level (P < ."( Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial.
Butler, J; Filippatos, G; Gheorghiade, M; Greene, SJ; Kraigher-Krainer, E; Lam, CS; Maggioni, AP; Müller, K; Pieske, B; Ponikowski, P; Roessig, L; Samano, ET; Shah, SJ; Solomon, SD, 2015)		1.04
" Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF."( Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial.
Butler, J; Filippatos, G; Gheorghiade, M; Greene, SJ; Kraigher-Krainer, E; Lam, CS; Maggioni, AP; Müller, K; Pieske, B; Ponikowski, P; Roessig, L; Samano, ET; Shah, SJ; Solomon, SD, 2015)		1.11
" Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen."( Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
Ackerstaff, J; Becker-Pelster, EM; Fey, P; Follmann, M; Geiss, V; Gerisch, M; Griebenow, N; Jautelat, R; Kern, A; Knorr, A; Kretschmer, A; Kroh, W; Lang, D; Li, V; Lustig, K; Mittendorf, J; Mondritzki, T; Redlich, G; Sandner, P; Schirok, H; Schlemmer, KH; Stasch, JP; Straub, A; Tinel, H; Trübel, H; Wunder, F, 2017)		0.7
" This study will also extend the prior dosing experience with vericiguat in HF by studying the safety and efficacy of a 15 mg dose."( Rationale and Design of the VITALITY-HFpEF Trial.
Anstrom, KJ; Armstrong, PW; Bamber, L; Blaustein, RO; Butler, J; Carvalho, F; Ezekowitz, J; Hernandez, AF; Lam, CSP; O'Connor, CM; Pieske, B; Ponikowski, P; Roessig, L; Shah, SJ; Solomon, SD; Voors, AA; Wu, Y, 2019)		0.75
" The distribution of steady-state doses in VICTORIA was similar across CL/F quartiles, suggesting that the ability to reach and maintain dosing at the target 10-mg dose was not related to vericiguat exposure."( Population Pharmacokinetics of Vericiguat in Patients With Heart Failure With Reduced Ejection Fraction: An Integrated Analysis.
Armstrong, PW; Arrington, L; Becker, C; Blaustein, RO; Gheyas, F; Meyer, M; Passarell, J; Patel, Y; Trujillo, ME; Wenning, L, 2022)		1.2
" The safety of the vericiguat, according to our review, is not up to the standards, especially with a higher dosage of vericiguat."( Efficacy and Safety of Vericiguat for Treatment of Heart Failure: A Systematic Review.
Ahmed, SH; Asghar, MS; Irfan, M; Jawed, S; Rahmat, ZS; Shaikh, TG; Ullah, I; Waseem, S, 2023)		1.55
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
soluble guanylate cyclase activatorAny compound that binds to and activates soluble guanylate cyclase (EC 4.6.1.2).
vasodilator agentA drug used to cause dilation of the blood vessels.
antihypertensive agentAny drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (4)

ClassDescription
aminopyrimidineA member of the class of pyrimidines that is pyrimidine substituted by at least one amino group and its derivatives.
pyrazolopyridine
carbamate esterAny ester of carbamic acid or its N-substituted derivatives.
organofluorine compoundAn organofluorine compound is a compound containing at least one carbon-fluorine bond.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (2)

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Cytochrome P450 3A4Homo sapiens (human)MEC0.30000.03000.21000.3000AID1448980
Guanylate cyclase soluble subunit alpha-1Rattus norvegicus (Norway rat)MEC0.30000.03000.21000.3000AID1448980
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (19)

Processvia Protein(s)Taxonomy
lipid hydroxylationCytochrome P450 3A4Homo sapiens (human)
lipid metabolic processCytochrome P450 3A4Homo sapiens (human)
steroid catabolic processCytochrome P450 3A4Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 3A4Homo sapiens (human)
steroid metabolic processCytochrome P450 3A4Homo sapiens (human)
cholesterol metabolic processCytochrome P450 3A4Homo sapiens (human)
androgen metabolic processCytochrome P450 3A4Homo sapiens (human)
estrogen metabolic processCytochrome P450 3A4Homo sapiens (human)
alkaloid catabolic processCytochrome P450 3A4Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 3A4Homo sapiens (human)
calcitriol biosynthetic process from calciolCytochrome P450 3A4Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 3A4Homo sapiens (human)
vitamin D metabolic processCytochrome P450 3A4Homo sapiens (human)
vitamin D catabolic processCytochrome P450 3A4Homo sapiens (human)
retinol metabolic processCytochrome P450 3A4Homo sapiens (human)
retinoic acid metabolic processCytochrome P450 3A4Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 3A4Homo sapiens (human)
aflatoxin metabolic processCytochrome P450 3A4Homo sapiens (human)
oxidative demethylationCytochrome P450 3A4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (23)

Processvia Protein(s)Taxonomy
monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
steroid bindingCytochrome P450 3A4Homo sapiens (human)
iron ion bindingCytochrome P450 3A4Homo sapiens (human)
protein bindingCytochrome P450 3A4Homo sapiens (human)
steroid hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
retinoic acid 4-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
oxidoreductase activityCytochrome P450 3A4Homo sapiens (human)
oxygen bindingCytochrome P450 3A4Homo sapiens (human)
enzyme bindingCytochrome P450 3A4Homo sapiens (human)
heme bindingCytochrome P450 3A4Homo sapiens (human)
vitamin D3 25-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
caffeine oxidase activityCytochrome P450 3A4Homo sapiens (human)
quinine 3-monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
testosterone 6-beta-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 8,9 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 11,12 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 14,15 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
aromatase activityCytochrome P450 3A4Homo sapiens (human)
vitamin D 24-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
estrogen 16-alpha-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
estrogen 2-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
1,8-cineole 2-exo-monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (3)

Processvia Protein(s)Taxonomy
cytoplasmCytochrome P450 3A4Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 3A4Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 3A4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (50)

Assay IDTitleYearJournalArticle
AID1448989Terminal half life in iv dosed Wistar rat blood after 24 hrs by LC-MS analysis2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449025Antihypertensive activity in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as reduction in Kim-1 expression at 3 to 10 mg/kg administered qd via oral gavage up to 21 days2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448988Clearance in iv dosed Beagle dog blood after 24 hrs by LC-MS analysis2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449009Stimulation of rat sGC expressed in CHO cells using GTP as substrate assessed as increase in cGMP formation treated for 6 mins by luminescence assay2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449003Inhibition of human liver microsomes CYP3A4 using testosterone as substrate preincubated with compound followed by substrate addition2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449029Effect on mortality in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as survival rate at 3 mg/kg administered qd via oral gavage up to 21 days (Rvb = 25%)2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449028Effect on mortality in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as increase in survival rate administered qd via oral gavage up to 21 days2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449008Stimulation of sGC (unknown origin) using alpha-[32P]-GTP as substrate assessed as increase in [32P]-cGMP formation at 100 uM in presence of sGC inhibitor ODQ2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449002Inhibition of human liver microsomes CYP3A4 using testosterone as substrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448992Oral bioavailability in Beagle dog administered via oral gavage after 24 hrs by LC-MS analysis2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448986Volume of distribution at steady state in iv dosed Beagle dog after 24 hrs by LC-MS analysis2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449006Stimulation of sGC (unknown origin) using alpha-[32P]-GTP as substrate assessed as increase in [32P]-cGMP formation at 0.01 to 100 uM relative to basal control2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449001Inhibition of human liver microsomes CYP3A4 using midazolam as substrate preincubated with compound followed by substrate addition2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448998Inhibition of human liver microsomes CYP2C19 using S-mephenytoin as substrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448996Inhibition of human liver microsomes CYP2C8 using amodiaquine as substrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449019Cardiotoxicity in Wistar rat assessed as effect on left ventricular diastolic pressure administered for 20 mins2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448994Inhibition of human liver microsomes CYP2A6 using coumarin as substrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449017Antihypertensive activity in Wistar Langendorff-perfused heart rat model assessed as reduction in coronary perfusion pressure administered for 20 mins2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448993Inhibition of human liver microsomes CYP1A2 using phenacetin as substrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449014Inhibition of phenylephrine-induced contractions in Chinchilla rabbit aortic rings administered at the beginning of the last resting period of 28 mins2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449005Drug metabolism in human hepatocytes assessed as CYP-mediated methyl 4,6-diamino-2-(5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-ylcarbamate metabolite formation2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449026Antihypertensive activity in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as reduction in osteopontin expression at 3 to 10 mg/kg administered qd via oral gavage up to 21 days2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449023Antihypertensive activity in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as reduction in heart hypertrophy in left ventricle administered qd via oral gavage up to 21 days2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449027Antihypertensive activity in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as reduction in proteinuria administered qd via oral gavage up to 21 days2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449007Stimulation of sGC (unknown origin) using alpha-[32P]-GTP as substrate assessed as increase in [32P]-cGMP formation at 100 uM in presence of DEA/NO complex relative to basal control2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449016Vasorelaxant activity in nirate-tolerant Chinchilla rabbit saphenous artery ring administered at the beginning of the last resting period of 28 mins in presence of sorbide dinitrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449030Effect on mortality in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as survival rate at 10 mg/kg administered qd via oral gavage up to 21 days (Rvb = 25%)2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448991Oral bioavailability in Wistar rat administered via oral gavage after 24 hrs by LC-MS analysis2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448984Inhibition of phenylephrine-induced contractions in dog femoral vein after 15 to 20 mins post phenylephrine-induced contraction2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449012Stimulation of rat sGC expressed in CHO cells using GTP as substrate assessed as increase in cGMP formation treated for 6 mins in presence of sGC inhibitor ODQ by luminescence assay2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449000Inhibition of human liver microsomes CYP3A4 using midazolam as substrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449004Drug metabolism in human hepatocytes assessed as CYP-mediated (2S,3S,4S,5R,6R)-6-(6-amino-2-(5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-5-(methoxycarbonylamino)pyrimidin-4-ylamino)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid met2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449013Inhibition of phenylephrine-induced contractions in Chinchilla rabbit saphenous artery rings administered at the beginning of the last resting period of 28 mins2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448990Terminal half life in iv dosed Beagle dog blood after 24 hrs by LC-MS analysis2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448985Volume of distribution at steady state in iv dosed Wistar rat after 24 hrs by LC-MS analysis2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449010Stimulation of rat sGC expressed in CHO cells using GTP as substrate assessed as increase in cGMP formation treated for 6 mins in presence of 30 nM SNAP by luminescence assay2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448981Clearance in rat hepatocytes at 1 uM up to 90 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448997Inhibition of human liver microsomes CYP2C9 using diclofenac as substrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449018Cardiotoxicity in Wistar rat assessed as effect on heart rate administered for 20 mins2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449024Antihypertensive activity in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as reduction in plasma ANP levels at 3 to 10 mg/kg administered qd via oral gavage up to 21 days2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449031Inhibition of U46619-induced contractions in porcine coronary artery rings2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449015Vasorelaxant activity in normal Chinchilla rabbit saphenous artery ring administered at the beginning of the last resting period of 28 mins2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448980Stimulation of rat recombinant sGCalpha1 subunit expressed in CHO cells using alpha-[32P]GTP as substrate assessed as >=3 fold increase in [32P]cGMP formation after 10 mins by radioimmunoassay2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449022Antihypertensive activity in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as reduction in heart hypertrophy in right ventricle administered qd via oral gavage up to 21 days relative to control2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449011Stimulation of rat sGC expressed in CHO cells using GTP as substrate assessed as increase in cGMP formation treated for 6 mins in presence of 100 nM SNAP by luminescence assay2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449021Antihypertensive activity in L-NAME-treated renin transgenic rat co-expressing RenTG(mRRen2)27 assessed as reduction in systolic blood pressure increase at 3 to 10 mg/kg, administered qd via oral gavage up to 21 days2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448995Inhibition of human liver microsomes CYP2B6 using bupropion as substrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448987Clearance in iv dosed Wistar rat blood after 24 hrs by LC-MS analysis2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1448999Inhibition of human liver microsomes CYP2D6 using dextromethorphan as substrate2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
AID1449020Cardiotoxicity in Wistar rat assessed as effect on contractility administered for 20 mins2017Journal of medicinal chemistry, 06-22, Volume: 60, Issue:12
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (109)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's11 (10.09)24.3611
2020's98 (89.91)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 82.66

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index82.66 (24.57)
Research Supply Index4.94 (2.92)
Research Growth Index5.12 (4.65)
Search Engine Demand Index143.65 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (82.66)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials27 (24.11%)5.53%
Reviews28 (25.00%)6.00%
Case Studies1 (0.89%)4.05%
Observational0 (0.00%)0.25%
Other56 (50.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
nitrates
Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical.		7.3110monovalent inorganic anion;
nitrogen oxoanion;
reactive nitrogen species
uric acid
Uric Acid: An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN.. uric acid : An oxopurine that is the final oxidation product of purine metabolism.. 6-hydroxy-1H-purine-2,8(7H,9H)-dione : A tautomer of uric acid having oxo groups at C-2 and C-8 and a hydroxy group at C-6.. 7,9-dihydro-1H-purine-2,6,8(3H)-trione : An oxopurine in which the purine ring is substituted by oxo groups at positions 2, 6, and 8.		8.1710uric acidEscherichia coli metabolite;
human metabolite;
mouse metabolite
urea
pseudourea: clinical use; structure. isourea : A carboximidic acid that is the imidic acid tautomer of urea, H2NC(=NH)OH, and its hydrocarbyl derivatives.		4.3320isourea;
monocarboxylic acid amide;
one-carbon compound		Daphnia magna metabolite;
Escherichia coli metabolite;
fertilizer;
flour treatment agent;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
eicosapentaenoic acid ethyl ester
[no description available]		3.3510
hydralazine
Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent.. hydralazine : The 1-hydrazino derivative of phthalazine; a direct-acting vasodilator that is used as an antihypertensive agent.		2.3110azaarene;
hydrazines;
ortho-fused heteroarene;
phthalazines		antihypertensive agent;
vasodilator agent
nitroglycerin
Nitroglycerin: A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.. nitroglycerol : A nitrate ester that is glycerol in which nitro group(s) replace the hydrogen(s) attached to one or more of the hydroxy groups.. nitroglycerin : A nitroglycerol that is glycerol in which the hydrogen atoms of all three hydroxy groups are replaced by nitro groups. It acts as a prodrug, releasing nitric oxide to open blood vessels and so alleviate heart pain.		9.0221nitroglycerolexplosive;
muscle relaxant;
nitric oxide donor;
prodrug;
tocolytic agent;
vasodilator agent;
xenobiotic
isosorbide dinitrate
Isosorbide Dinitrate: A vasodilator used in the treatment of ANGINA PECTORIS. Its actions are similar to NITROGLYCERIN but with a slower onset of action.		5.0721glucitol derivative;
nitrate ester		nitric oxide donor;
vasodilator agent
isosorbide-5-mononitrate
isosorbide-5-mononitrate: for prevention of angina pectoris; structure given in first source; a Russian drug		4.7211glucitol derivative;
nitrate ester		nitric oxide donor;
vasodilator agent
ng-nitroarginine methyl ester
NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.		2.1510alpha-amino acid ester;
L-arginine derivative;
methyl ester;
N-nitro compound		EC 1.14.13.39 (nitric oxide synthase) inhibitor
valsartan
Valsartan: A tetrazole derivative and ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKER that is used to treat HYPERTENSION.. valsartan : A monocarboxylic acid amide consisting of L-valine in which the amino hydrogens have been replaced by a pentanoyl and a [2'-(1H-tetrazol-5-yl)biphenyl]-4-yl]methyl group. It exhibits antihypertensive activity.		8.2471biphenylyltetrazole;
monocarboxylic acid amide;
monocarboxylic acid		angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
moxifloxacin
Moxifloxacin: A fluoroquinolone that acts as an inhibitor of DNA TOPOISOMERASE II and is used as a broad-spectrum antibacterial agent.. moxifloxacin : A quinolone that consists of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid bearing a cyclopropyl substituent at position 1, a fluoro substitiuent at position 6, a (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl group at position 7 and a methoxy substituent at position 8. A member of the fluoroquinolone class of antibacterial agents.		3.9911aromatic ether;
cyclopropanes;
fluoroquinolone antibiotic;
pyrrolidinopiperidine;
quinolinemonocarboxylic acid;
quinolone antibiotic;
quinolone		antibacterial drug
eicosapentaenoic acid
icosapentaenoic acid : Any straight-chain, C20 polyunsaturated fatty acid having five C=C double bonds.. all-cis-5,8,11,14,17-icosapentaenoic acid : An icosapentaenoic acid having five cis-double bonds at positions 5, 8, 11, 14 and 17.		3.3510icosapentaenoic acid;
omega-3 fatty acid		anticholesteremic drug;
antidepressant;
antineoplastic agent;
Daphnia galeata metabolite;
fungal metabolite;
micronutrient;
mouse metabolite;
nutraceutical
bilirubin
[no description available]		2.4110biladienes;
dicarboxylic acid		antioxidant;
human metabolite;
mouse metabolite
bay 58-2667
BAY 58-2667: activates guanylyl cyclase; structure in first source. cinaciguat : A benzoic acid that is 4-(aminomethyl)benzoic acid in which the amino group is substituted by 4-carboxybutyl and 2-(2-{[4-(2-phenylethyl)benzyl]oxy}phenyl)ethyl groups. It is a soluble guanylate cyclase activator, used for the treatment of acute decompensated heart failure.		3.2510aromatic ether;
benzoic acids;
dicarboxylic acid;
tertiary amino compound		antihypertensive agent;
soluble guanylate cyclase activator;
vasodilator agent
sacubitril
[no description available]		7.451biphenyls
bay 41-8543
BAY 41-8543: structure in first source		3.1810pyrazolopyridine
acebutolol
alpha-D-glucosyl-(1->4)-alpha-D-mannose : An alpha-D-glucosyl-(1->4)-D-mannopyranose in which the anomeric hydroxy group has alpha configuration.		3.4110alpha-D-glucosyl-(1->4)-D-mannopyranose
bay 63-2521
riociguat: guanylate cyclase stimulator; structure in first source. riociguat : A carbamate ester that is the methyl ester of {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamic acid. It is used for treatment of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension		4.9940aminopyrimidine;
carbamate ester;
organofluorine compound;
pyrazolopyridine		antihypertensive agent;
soluble guanylate cyclase activator
omecamtiv mecarbil
[no description available]		4.3320ureas
bay 60-4552
BAY 60-4552: a riociguat metabolite that activates soluble guanylate cyclase. nelociguat : A member of the class of pyrazolopyridines that is 1H-pyrazolo[3,4-b]pyridine which is substituted by a 2-fluorobenzyl and 4,6-diamino-5-[(methoxycarbonyl)amino]pyrimidin-2-yl groups at positions 1 and 3, respectively. It is an active metabolite of riociguat and a soluble guanylate cyclase stimulator developed by Bayer for the treatment of erectile dysfunction and heart failure.		2.1510aminopyrimidine;
carbamate ester;
monofluorobenzenes;
pyrazolopyridine		antihypertensive agent;
drug metabolite;
soluble guanylate cyclase activator;
vasodilator agent
cardiovascular agents
Cardiovascular Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume.		6.3531
natriuretic peptide, brain
Natriuretic Peptide, Brain: A PEPTIDE that is secreted by the BRAIN and the HEART ATRIA, stored mainly in cardiac ventricular MYOCARDIUM. It can cause NATRIURESIS; DIURESIS; VASODILATION; and inhibits secretion of RENIN and ALDOSTERONE. It improves heart function. It contains 32 AMINO ACIDS.		10.74135polypeptide
cyclic gmp
Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed). 3',5'-cyclic GMP : A 3',5'-cyclic purine nucleotide in which the purine nucleobase is specified as guanidine.		11.8613',5'-cyclic purine nucleotide;
guanyl ribonucleotide		Escherichia coli metabolite;
human metabolite;
mouse metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
guanosine monophosphate
Guanosine Monophosphate: A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.. guanosine 5'-monophosphate : A purine ribonucleoside 5'-monophosphate having guanine as the nucleobase.		8.9220guanosine 5'-phosphate;
purine ribonucleoside 5'-monophosphate		biomarker;
Escherichia coli metabolite;
metabolite;
mouse metabolite
sildenafil citrate
Sildenafil Citrate: A PHOSPHODIESTERASE TYPE-5 INHIBITOR; VASODILATOR AGENT and UROLOGICAL AGENT that is used in the treatment of ERECTILE DYSFUNCTION and PRIMARY PULMONARY HYPERTENSION.. sildenafil citrate : The citrate salt of sildenafil.		4.6831citrate saltEC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor;
vasodilator agent
ferric carboxymaltose
ferric carboxymaltose: effective for treatment of postpartum anemia		3.4110
ConditionIndicatedRelationship StrengthStudiesTrials
Cardiac Failure
[description not available]		018.9312533
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.		120.9312533
Left Ventricular Dysfunction
[description not available]		012.822313
Blood Pressure, Low
[description not available]		011.361210
Drop Attack
[description not available]		010.07109
Hypotension
Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.		011.361210
Syncope
A transient loss of consciousness and postural tone caused by diminished blood flow to the brain (i.e., BRAIN ISCHEMIA). Presyncope refers to the sensation of lightheadedness and loss of strength that precedes a syncopal event or accompanies an incomplete syncope. (From Adams et al., Principles of Neurology, 6th ed, pp367-9)		010.07109
Ventricular Dysfunction, Left
A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.		012.822313
Blood Pressure, High
[description not available]		03.9230
Hypertension
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.		03.9230
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.4110
Arteriosclerosis, Coronary
[description not available]		02.4110
Coronary Artery Disease
Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.		07.4110
Symptom Cluster
[description not available]		05.6822
Syndrome
A characteristic symptom complex.		05.6822
Chronic Illness
[description not available]		012.261411
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		012.261411
Hyperpotassemia
[description not available]		04.7211
Hyperkalemia
Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)		04.7211
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		02.4110
Mitral Incompetence
[description not available]		03.9911
Mitral Valve Insufficiency
Backflow of blood from the LEFT VENTRICLE into the LEFT ATRIUM due to imperfect closure of the MITRAL VALVE. This can lead to mitral valve regurgitation.		03.9911
Death, Sudden
The abrupt cessation of all vital bodily functions, manifested by the permanent loss of total cerebral, respiratory, and cardiovascular functions.		03.9911
Cardiac Remodeling, Ventricular
[description not available]		04.4530
Arrhythmia
[description not available]		07.610
Cardiovascular Stroke
[description not available]		02.610
Arrhythmias, Cardiac
Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.		02.610
Myocardial Infarction
NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).		07.610
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.		111.8799
Apolipoprotein B-100, Familial Defective
[description not available]		03.1710
Hyperlipoproteinemia Type II
A group of familial disorders characterized by elevated circulating cholesterol contained in either LOW-DENSITY LIPOPROTEINS alone or also in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins).		03.1710
Smoking Cessation
Discontinuing the habit of SMOKING.		03.1710
Cardiac Death
[description not available]		02.2510
Disease Exacerbation
[description not available]		02.2510
Auricular Fibrillation
[description not available]		03.711
Atrial Fibrillation
Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.		08.711
Pulmonary Hypertension
[description not available]		0310
Hypertension, Pulmonary
Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.		0310