Page last updated: 2024-12-11
zoniporide
Description
Research Excerpts
Clinical Trials
Roles
Classes
Pathways
Study Profile
Bioassays
Related Drugs
Related Conditions
Protein Interactions
Research Growth
Market Indicators
Description
zoniporide: inhibits sodium-hydrogen exchanger isoform-1 (NHE-1) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
Cross-References
| ID Source | ID |
|---|---|
| PubMed CID | 6433110 |
| CHEMBL ID | 355862 |
| SCHEMBL ID | 611159 |
| MeSH ID | M0385337 |
Synonyms (26)
| Synonym |
|---|
| zoniporide [inn] |
| bdbm50097898 |
| n-(5-cyclopropyl-1-quinolin-5-yl-1h-pyrazole-4-carbonyl)-guanidine |
| zoniporide |
| CHEMBL355862 , |
| 5-cyclopropyl-n-(diaminomethylidene)-1-quinolin-5-ylpyrazole-4-carboxamide |
| zoniporide [inn:ban] |
| unii-8841r2ujpg |
| n-carbamimidoyl-5-cyclopropyl-1-(quinolin-5-yl)-1h-pyrazole-4-carboxamide |
| 8841r2ujpg , |
| 241800-98-6 |
| cp-597,396 |
| (1-(quinolin-5-yl)-5-cyclopropyl-1h-pyrazole-4-carbonyl)guanidine hydrochloride monohydrate |
| SCHEMBL611159 |
| n-(5-cyclopropyl-1-quinolin-5-yl-1h-pyrazole4-carbonyl)-guanidine |
| GDXBRVCQGGKXJY-UHFFFAOYSA-N |
| [5-cyclopropyl-1-(quinolin-5-yl)-1h-pyrazole-4-carbonyl]guanidine |
| DTXSID0057883 |
| NCGC00386683-01 |
| PS-18710 |
| Q27269884 |
| CS-0024861 |
| mfcd32004449 |
| SY284545 |
| n-carbamimidoyl-5-cyclopropyl-1-(5-quinolyl)pyrazole-4-carboxamide |
| F78290 |
Research Excerpts
Overview
Zoniporide (CP-597,396) is a potent and selective inhibitor of NHE-1. It exhibits high aqueous solubility and acceptable pharmacokinetics for intravenous administration.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Zoniporide (CP-597,396) is a potent and selective inhibitor of NHE-1, which exhibits high aqueous solubility and acceptable pharmacokinetics for intravenous administration. " | ( Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. Allen, MC; Brown, JA; Buchholz, AR; Cook, ER; Day, WW; Guzman-Perez, A; Hamanaka, ES; Hill, RJ; Kennedy, SP; Knight, DR; Kowalczyk, PJ; Marala, RB; Mularski, CJ; Novomisle, WA; Ruggeri, RB; Tracey, WR; Wester, RT, 2001) | 2.12 |
| "Zoniporide is a potent cardioprotective agent and activation of STAT3 plays a critical role in the cardioprotective action of zoniporide. " | ( Critical role of the STAT3 pathway in the cardioprotective efficacy of zoniporide in a model of myocardial preservation - the rat isolated working heart. Gao, L; Hicks, M; Kwan, J; Macdonald, PS; Sun, L; Tsun, J; Watson, A, 2011) | 2.05 |
Pharmacokinetics
| Excerpt | Reference | Relevance |
|---|---|---|
| "The pharmacokinetic properties of drugs may be altered by kinetic deuterium isotope effects." | ( Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. Clark, AJ; Gao, H; Obach, RS; Ripp, SL; Schildknegt, K; Sharma, R; Spracklin, DK; Strelevitz, TJ; Tremaine, LM; Vaz, AD, 2012) | 0.38 |
Bioavailability
| Excerpt | Reference | Relevance |
|---|---|---|
| "The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs." | ( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019) | 0.51 |
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
Protein Targets (3)
Inhibition Measurements
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Sodium/hydrogen exchanger 1 | Homo sapiens (human) | IC50 (µMol) | 0.0590 | 0.0050 | 0.5601 | 3.5000 | AID1341120; AID1341847; AID1411094; AID143806 |
| Sodium/hydrogen exchanger 3 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 500.0000 | 0.0093 | 0.6086 | 2.4000 | AID1341123; AID1341851; AID1411098 |
| Sodium/hydrogen exchanger 2 | Homo sapiens (human) | IC50 (µMol) | 12.0000 | 2.0000 | 4.0143 | 9.2000 | AID1341121; AID1341850; AID1411095; AID143808 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Biological Processes (42)
Molecular Functions (12)
Ceullar Components (16)
Bioassays (46)
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1347159 | Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1346986 | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1346987 | P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1347160 | Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID12016 | Concentration in the plasma after intravenous administration of 1 mg/kg in rat | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID731933 | Fraction unbound in human plasma | 2013 | ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1 | Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. |
| AID1219920 | Half life in Hartley guinea pig at 2.5 mg/kg, po | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID731935 | Half life in human liver S9 fraction in presence of NADPH | 2013 | ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1 | Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. |
| AID232710 | Selectivity ratio of NHE-1 verus NHE-2 was determined | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID1219908 | AUC in Hartley guinea pig at 1 mg/kg, iv | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID1215693 | Drug metabolism in human liver S9 fraction assessed as aldehyde oxidase-mediated 2-oxo-metabolite formation at 10 uM by spectrometry | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Aug, Volume: 40, Issue:8 | Effect of structural variation on aldehyde oxidase-catalyzed oxidation of zoniporide. |
| AID731931 | Plasma clearance in iv dosed human | 2013 | ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1 | Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. |
| AID701663 | Volume of distribution at steady state in jugular and femoral vein precannulated Sprague-Dawley rat at 1 mg/kg, iv by LC/MS/MS analysis | 2012 | Journal of medicinal chemistry, Aug-23, Volume: 55, Issue:16 | Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat. |
| AID12100 | Half life after intravenous administration of 1 mg/kg in rat | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID731932 | Ratio of fraction unbound in blood to fraction unbound in plasma in human | 2013 | ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1 | Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. |
| AID1525699 | Substrate activity at aldehyde oxidase in rat liver cytosol assessed as enzyme-mediated drug uptake at 1 uM | 2019 | Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24 | Metabolism by Aldehyde Oxidase: Drug Design and Complementary Approaches to Challenges in Drug Discovery. |
| AID1215671 | Drug metabolism in pooled human hepatocytes assessed as aldehyde oxidase-mediated drug metabolism at 10 uM up to 120 mins by HPLC analysis in presence of 25 uM of hydralazine | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 40, Issue:7 | Hydralazine as a selective probe inactivator of aldehyde oxidase in human hepatocytes: estimation of the contribution of aldehyde oxidase to metabolic clearance. |
| AID8327 | Bioavailability from area under the curve at time 0 to infinity after intravenous administration of 1 mg/kg in dog | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID11227 | Plasma clearance after intravenous administration of 1 mg/kg in rat | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID1219922 | Cmax in Sprague-Dawley rat at 2.5 mg/kg, po | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID1219923 | Half life in Sprague-Dawley rat at 2.5 mg/kg, po | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID143808 | In vitro concentration of compound required to inhibit NHE-2 mediated intracellular maximal pH recovery by 50% | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID1525700 | Substrate activity at aldehyde oxidase in guinea pig liver cytosol assessed as enzyme-mediated drug uptake at 1 uM | 2019 | Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24 | Metabolism by Aldehyde Oxidase: Drug Design and Complementary Approaches to Challenges in Drug Discovery. |
| AID9545 | Plasma protein binding was determined after intravenous administration of 1 mg/kg in dog | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID1215672 | Drug metabolism in pooled human hepatocytes assessed as aldehyde oxidase-mediated drug metabolism at 10 uM up to 120 mins by HPLC analysis in presence of 50 uM of hydralazine | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 40, Issue:7 | Hydralazine as a selective probe inactivator of aldehyde oxidase in human hepatocytes: estimation of the contribution of aldehyde oxidase to metabolic clearance. |
| AID701662 | Oral bioavailability in jugular and femoral vein precannulated Sprague-Dawley rat plasma at 5 mg/kg by LC/MS/MS analysis | 2012 | Journal of medicinal chemistry, Aug-23, Volume: 55, Issue:16 | Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat. |
| AID701665 | Clearance in jugular and femoral vein precannulated Sprague-Dawley rat at 1 mg/kg, iv by LC/MS/MS analysis relative to hepatic blood flow | 2012 | Journal of medicinal chemistry, Aug-23, Volume: 55, Issue:16 | Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat. |
| AID11116 | Steady state volume of distribution for the compound after intravenous administration of 1 mg/kg in rat | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID1219921 | AUC in Sprague-Dawley rat at 2.5 mg/kg, po | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID1219919 | Cmax in Hartley guinea pig at 2.5 mg/kg, po | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID9905 | Steady state volume of distribution for the compound after intravenous administration of 1 mg/kg in dog | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID143806 | In vitro concentration required to inhibit NHE-1 mediated intracellular maximal pH recovery by 50% | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID9105 | Concentration in the plasma after intravenous administration of 1 mg/kg in dog | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID1525698 | Substrate activity at aldehyde oxidase in human liver cytosol assessed as enzyme-mediated drug uptake at 1 uM | 2019 | Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24 | Metabolism by Aldehyde Oxidase: Drug Design and Complementary Approaches to Challenges in Drug Discovery. |
| AID701664 | Mean resident time in jugular and femoral vein precannulated Sprague-Dawley rat at 1 mg/kg, iv by LC/MS/MS analysis | 2012 | Journal of medicinal chemistry, Aug-23, Volume: 55, Issue:16 | Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat. |
| AID12354 | Bioavailability from area under the curve at time 0 to infinity after intravenous administration of 1 mg/kg in rat | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID1219910 | AUC in Sprague-Dawley rat at 1 mg/kg, iv | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID8731 | Plasma clearance after intravenous administration of 1 mg/kg in dog | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID10093 | Half life after intravenous administration of 1 mg/kg in dog | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| AID1219918 | AUC in Hartley guinea pig at 2.5 mg/kg, po | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID1219911 | Half life in Sprague-Dawley rat at 1 mg/kg, iv | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID1525701 | Substrate activity at aldehyde oxidase in human hepatocytes assessed as enzyme-mediated drug uptake at 1 uM | 2019 | Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24 | Metabolism by Aldehyde Oxidase: Drug Design and Complementary Approaches to Challenges in Drug Discovery. |
| AID1219909 | Half life in Hartley guinea pig at 1 mg/kg, iv | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3 | Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs. |
| AID1215690 | Half life in human liver S9 fraction assessed as aldehyde oxidase-mediated 2-oxo-metabolite formation at 1 uM by spectrometry | 2012 | Drug metabolism and disposition: the biological fate of chemicals, Aug, Volume: 40, Issue:8 | Effect of structural variation on aldehyde oxidase-catalyzed oxidation of zoniporide. |
| AID13462 | Plasma protein binding was determined after intravenous administration of 1 mg/kg in rat | 2001 | Bioorganic & medicinal chemistry letters, Mar-26, Volume: 11, Issue:6 | Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
Research
Studies (45)
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 16 (35.56) | 29.6817 |
| 2010's | 26 (57.78) | 24.3611 |
| 2020's | 3 (6.67) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
Market Indicators
Research Demand Index: 22.43
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 (22.43) All Compounds (24.57) |
Study Types
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 2 (4.44%) | 5.53% |
| Reviews | 2 (4.44%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 41 (91.11%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||