BAY 60-4552: a riociguat metabolite that activates soluble guanylate cyclase [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
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. [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]
| ID Source | ID |
|---|---|
| PubMed CID | 11690019 |
| CHEMBL ID | 4072580 |
| CHEBI ID | 149785 |
| SCHEMBL ID | 248358 |
| MeSH ID | M0570419 |
| Synonym |
|---|
| C16105 |
| bay60-4552 |
| methyl (4,6-diamino-2-{1-[(2-fluorophenyl)methyl]-1h-pyrazolo[3,4-b]pyridin-3-yl}pyrimidin-5-yl)carbamate |
| bay 60-4552 |
| nelociguatum |
| methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate |
| CHEBI:149785 |
| 625115-52-8 |
| bay-60-4552 |
| nelociguat |
| unii-m2a18ll56o |
| nelociguat [inn] |
| methyl (4,6-diamino-2-(1-((2-fluorophenyl)methyl)-1h-pyrazolo(3,4-b)pyridin-3-yl)pyrimidin-5-yl)carbamate |
| carbamic acid, (4,6-diamino-2-(1-((2-fluorophenyl)methyl)-1h-pyrazolo(3,4-b)pyridin-3-yl)-5-pyrimidinyl)-, methyl ester |
| carbamic acid, n-(4,6-diamino-2-(1-((2-fluorophenyl)methyl)-1h-pyrazolo(3,4-b)pyridin-3-yl)-5-pyrimidinyl)-, methyl ester |
| m2a18ll56o , |
| riociguat metabolite m1 |
| nelociguat [who-dd] |
| SCHEMBL248358 |
| CS-M2183 |
| AKOS022186224 |
| methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo-[3,4-b]pyridin-3-yl]-5-pyrimidinylcarbamate |
| methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinylcarbamate |
| FTQHGWIXJSSWOY-UHFFFAOYSA-N |
| c19h17fn8o2 |
| methyl (4,6-diamino-2-(1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)carbamate |
| methyl [4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate |
| HY-78237 |
| methyl n-[4,6-diamino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate |
| BCP16721 |
| SB17528 |
| AMY7846 |
| CHEMBL4072580 |
| Q27283388 |
| MS-27009 |
| methyl(4,6-diamino-2-(1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)carbamate |
| Excerpt | Reference | Relevance |
|---|---|---|
| " A single dose was given on Day 1, followed by a 48-h pharmacokinetic profile." | ( Pharmacokinetics of the Soluble Guanylate Cyclase Stimulator Riociguat in Healthy Young Chinese Male Non-Smokers and Smokers: Results of a Randomized, Double-Blind, Placebo-Controlled Study. Becker, C; Blode, H; Cui, Y; Frey, R; Unger, S; Wang, Y; Wang, Z; Yoshikawa, K; Zhang, H; Zhao, X, 2016) | 0.43 |
| "Thirty-six subjects (18 smokers; 18 non-smokers) were randomized and provided valid pharmacokinetic data." | ( Pharmacokinetics of the Soluble Guanylate Cyclase Stimulator Riociguat in Healthy Young Chinese Male Non-Smokers and Smokers: Results of a Randomized, Double-Blind, Placebo-Controlled Study. Becker, C; Blode, H; Cui, Y; Frey, R; Unger, S; Wang, Y; Wang, Z; Yoshikawa, K; Zhang, H; Zhao, X, 2016) | 0.43 |
| Excerpt | Relevance | Reference |
|---|---|---|
| " 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) | 0.46 |
| Role | Description |
|---|---|
| soluble guanylate cyclase activator | Any compound that binds to and activates soluble guanylate cyclase (EC 4.6.1.2). |
| antihypertensive agent | Any drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism. |
| drug metabolite | null |
| vasodilator agent | A drug used to cause dilation of the blood vessels. |
| [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] | |
| Class | Description |
|---|---|
| pyrazolopyridine | |
| monofluorobenzenes | Any member of the class of fluorobenzenes containing a mono- or poly-substituted benzene ring carrying a single fluorine substitutent. |
| carbamate ester | Any ester of carbamic acid or its N-substituted derivatives. |
| aminopyrimidine | A member of the class of pyrimidines that is pyrimidine substituted by at least one amino group and its derivatives. |
| [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 | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Cytochrome P450 3A4 | Homo sapiens (human) | MEC | 0.3000 | 0.0300 | 0.2100 | 0.3000 | AID1448980 |
| Guanylate cyclase soluble subunit alpha-1 | Rattus norvegicus (Norway rat) | MEC | 0.3000 | 0.0300 | 0.2100 | 0.3000 | AID1448980 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| cytoplasm | Cytochrome P450 3A4 | Homo sapiens (human) |
| endoplasmic reticulum membrane | Cytochrome P450 3A4 | Homo sapiens (human) |
| intracellular membrane-bounded organelle | Cytochrome P450 3A4 | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1448982 | Apparent permeability across apical to basolateral side in human Caco2 cells at 2 uM after 2 hrs by LC-MS analysis | 2017 | Journal 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. |
| AID1448981 | Clearance in rat hepatocytes at 1 uM up to 90 mins by LC-MS/MS analysis | 2017 | Journal 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. |
| AID1448983 | Efflux ratio of apparent permeability in human Caco2 cells | 2017 | Journal 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. |
| AID1448980 | Stimulation 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 radioimmunoassay | 2017 | Journal 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] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 0 (0.00) | 29.6817 |
| 2010's | 7 (100.00) | 24.3611 |
| 2020's | 0 (0.00) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
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 moderate demand-to-supply ratio for research on this compound.
| This Compound (17.49) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 1 (14.29%) | 5.53% |
| Reviews | 1 (14.29%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 5 (71.43%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||