Target Information

Target General Infomation
Target ID
T61622
Former ID
TTDS00451
Target Name
Renin, renal
Synonyms
Angiotensinogenase; Renin
Target Type
Successful
Disease Cardiovascular disorder [ICD10: I00-I99]
Glaucoma [ICD9: 365; ICD10: H40-H42]
Hypertension [ICD9: 401; ICD10: I10-I16]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Unspecified [ICD code not available]
Function
Renin is a highly specific endopeptidase, whose only knownfunction is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.
BioChemical Class
Peptidase
Target Validation
T61622
EC Number
EC 3.4.23.15
Drugs and Mode of Action
Drug(s) Aliskiren Drug Info Approved Hypertension [468044], [529282], [536836]
Remikiren Drug Info Approved Hypertension [536145]
CP-80794 Drug Info Phase 2 Hypertension [544930]
SPP-600 Drug Info Phase 2 Hypertension [521887]
SR-43845 Drug Info Phase 2 Glaucoma [544840]
TAK-272 Drug Info Phase 2 Type 2 diabetes [525048]
ACT-178882 Drug Info Phase 1 Cardiovascular disorder [548839]
CARD-024 Drug Info Phase 1 Cardiovascular disorder [524173]
VTP-27999 Drug Info Phase 1 Hypertension [523201]
Enalkiren Drug Info Discontinued in Phase 2 Glaucoma [544632]
FK-906 Drug Info Discontinued in Phase 2 Hypertension [545037]
ZANKIREN Drug Info Discontinued in Phase 2 Hypertension [545082]
RS-8891 Drug Info Discontinued in Phase 1 Hypertension [544648]
SPP-1148 Drug Info Discontinued in Phase 1 Hypertension [548440]
SPP-676 Drug Info Discontinued in Phase 1 Hypertension [548628]
A-74273 Drug Info Terminated Hypertension [544985]
BILA-2157BS Drug Info Terminated Hypertension [546173]
Ciprokiren Drug Info Terminated Hypertension [545961]
ES-1005 Drug Info Terminated Hypertension [545147]
JTP-2724 Drug Info Terminated Hypertension [546760]
JTP-4761 Drug Info Terminated Hypertension [546032]
KRI-1314 Drug Info Terminated Hypertension [545182]
SC-56525 Drug Info Terminated Hypertension [545665]
SQ-33800 Drug Info Terminated Hypertension [545186]
Inhibitor (H-261)Boc-His-Pro-Phe-His-Leu(OH)-Val-Ile-His-OH Drug Info [533442]
1-Hydroxy-2-Amino-3-Cyclohexylpropane Drug Info [551393]
1-Hydroxy-3-Methylbutane Drug Info [551393]
1-Methyl-2-Oxy-5,5-Dimethyl Pyrrolidine Drug Info [551393]
2-Cyclopropylmethylenepropanal Drug Info [551393]
2-Methyl-3-(2-Aminothiazolo)Propanal Drug Info [551374]
3-Phenyl-1,2-Propandiol Drug Info [551393]
A-74273 Drug Info [533789]
ACT-178882 Drug Info [532219]
Aliskiren Drug Info [537617]
BILA-2157BS Drug Info [534183]
Ciprokiren Drug Info [533865]
CP-305202 Drug Info [531120]
CP-80794 Drug Info [535823]
Dimethylformamide Drug Info [551397]
Enalkiren Drug Info [537925]
ES-1005 Drug Info [530272]
ES-6864 Drug Info [533425], [551871]
FK-906 Drug Info [533996]
Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro Drug Info [533536]
Iva-His-Pro-Phe-His-ACHPA-Leu-Phe-NH2 Drug Info [533493]
Iva-His-Pro-Phe-His-AHPPA-Leu-Phe-NH2 Drug Info [533493]
Iva-His-Pro-Phe-His-Sta-Leu-Phe-NH2 Drug Info [533493]
JTP-2724 Drug Info [546733]
JTP-4761 Drug Info [546033]
KRI-1314 Drug Info [533964]
N-Methyl-N-(Methylbenzyl)Formamide Drug Info [551374]
PP1-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O) Drug Info [530554]
PP2-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O) Drug Info [530554]
Pro-His-Pro-His-Leu-Phe-Val-Tyr Drug Info [533536]
Pro-His-Pro-His-Phe-Phe-Val-Tyr Drug Info [533536]
Pro-His-Pro-His-Phe-Phe-Val-Tyr-Lys Drug Info [533536]
Pro-His-Pro-Phe-His-Leu(CH2NH)Val-Ile-His-Lys Drug Info [533426]
Remikiren Drug Info [536145]
Renin inhibitors Drug Info [543623]
Ro-65-7219 Drug Info [531120]
Ro-66-1168 Drug Info [530066]
RS-8891 Drug Info [551182]
SC-56525 Drug Info [533654]
SPP-1148 Drug Info [544476]
SPP-600 Drug Info [531738]
SPP-676 Drug Info [544476]
SPP-800 Drug Info [543623]
SQ-33800 Drug Info [545187]
SR-43845 Drug Info [533331], [551871]
Sul-Pro-Phe-N-MeHis-LVA-Ile-Amp Drug Info [530554]
Sul-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O) Drug Info [530554]
VTP-27999 Drug Info [544476]
ZANKIREN Drug Info [530066]
Agonist CARD-024 Drug Info [543623]
Modulator JT-2724 Drug Info [1572605]
renin inhibitors (hypertension/congestive heart failure) Pfizer Drug Info [1572605]
TAK-272 Drug Info [549203]
Pathways
KEGG Pathway Renin-angiotensin system
PathWhiz Pathway Angiotensin Metabolism
Reactome Metabolism of Angiotensinogen to Angiotensins
WikiPathways ACE Inhibitor Pathway
Metabolism of Angiotensinogen to Angiotensins
References
Ref 468044(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4812).
Ref 521887ClinicalTrials.gov (NCT00376636) Phase IIa Safety and Efficacy Study of SPP635 in Mild to Moderate Hypertension. U.S. National Institutes of Health.
Ref 523201ClinicalTrials.gov (NCT01217736) Direct Renin Inhibition and the Kidney. U.S. National Institutes of Health.
Ref 524173ClinicalTrials.gov (NCT01757860) Safety and Pharmacokinetics Study of CARD-024 in Healthy Subjects. U.S. National Institutes of Health.
Ref 525048ClinicalTrials.gov (NCT02332824) A Phase 2 Dose-finding Study of TAK-272 in Patients With Type 2 Diabetes Mellitus and Microalbuminuria. U.S. National Institutes of Health.
Ref 5292822007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
Ref 536145Functional expression of the renin-angiotensin system in human podocytes. Am J Physiol Renal Physiol. 2006 Mar;290(3):F710-9. Epub 2005 Sep 27.
Ref 536836Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
Ref 544632Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000369)
Ref 544648Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000425)
Ref 544840Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001290)
Ref 544930Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001570)
Ref 544985Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001791)
Ref 545037Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001939)
Ref 545082Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002065)
Ref 545147Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002295)
Ref 545182Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002396)
Ref 545186Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002406)
Ref 545665Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004067)
Ref 545961Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005529)
Ref 546032Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005981)
Ref 546173Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006753)
Ref 546760Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010164)
Ref 548440Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025565)
Ref 548628Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027192)
Ref 548839Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029409)
Ref 530066J Med Chem. 2009 Jun 25;52(12):3689-702.Design and preparation of potent, nonpeptidic, bioavailable renin inhibitors.
Ref 530272The effect of the renin inhibitor ES-1005 on the expression of the kidney renin gene in sodium-depleted marmosets. J Hypertens. 1990 Dec;8(12):1143-6.
Ref 530554J Med Chem. 1991 Feb;34(2):633-42.Renin inhibitory peptides. Incorporation of polar, hydrophilic end groups into an active renin inhibitory peptide template and their evaluation in a human renin infused rat model and in conscious sodium-depleted monkeys.
Ref 531120J Med Chem. 2010 Nov 11;53(21):7490-520.Direct renin inhibitors as a new therapy for hypertension.
Ref 531738Effect of SPP 635, a renin inhibitor, on intraocular pressure in glaucomatous monkey eyes. Exp Eye Res. 2012 Jan;94(1):146-9.
Ref 532219Drug-drug interaction study of ACT-178882, a new renin inhibitor, and diltiazem in healthy subjects. Clin Drug Investig. 2013 Mar;33(3):207-13.
Ref 533331Effects of a renin inhibitor, SR 43845, and of captopril on blood pressure and plasma active renin in conscious sodium-replete macaca. J Hypertens Suppl. 1989 Apr;7(2):S33-5.
Ref 533425A highly potent and long-acting oral inhibitor of human renin. Hypertension. 1988 Jun;11(6 Pt 2):708-12.
Ref 533426J Med Chem. 1988 Sep;31(9):1839-46.Synthesis and biological activity of some transition-state inhibitors of human renin.
Ref 533442J Med Chem. 1987 Oct;30(10):1729-37.Renin inhibitors. Dipeptide analogues of angiotensinogen incorporating transition-state, nonpeptidic replacements at the scissile bond.
Ref 533493J Med Chem. 1985 Dec;28(12):1779-90.Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analogue inhibitors containing a novel analogue of statine.
Ref 533536J Med Chem. 1981 Apr;24(4):355-61.Inhibition of the renin-angiotensin system. A new approach to the therapy of hypertension.
Ref 533654Effects of SC-56525, a potent, orally active renin inhibitor, in salt-depleted and renal hypertensive dogs. Hypertension. 1995 Jul;26(1):95-100.
Ref 533789The orally active renin inhibitor A-74273. In vivo and in vitro morpholine ring metabolism in rats, dogs, and humans. Drug Metab Dispos. 1994 Nov-Dec;22(6):880-8.
Ref 533865Ciprokiren (Ro 44-9375). A renin inhibitor with increasing effects on chronic treatment. Hypertension. 1994 Aug;24(2):163-9.
Ref 533964KRI-1314: an orally effective inhibitor of human renin. Jpn J Pharmacol. 1993 Sep;63(1):109-19.
Ref 533996Antihypertensive efficacy of FK906, a novel human renin inhibitor. Clin Ther. 1993 May-Jun;15(3):539-48.
Ref 534183Comparative studies on differential inhibition of the renin - angiotensin system in the anesthetized guinea pig. Can J Physiol Pharmacol. 1995 Oct;73(10):1512-8.
Ref 535823Synergistic effect on reduction in blood pressure with coadministration of the renin inhibitor, CP-80,794, and the angiotensin converting enzyme inhibitor, captopril. J Cardiovasc Pharmacol. 1992 Jul;20(1):75-82.
Ref 536145Functional expression of the renin-angiotensin system in human podocytes. Am J Physiol Renal Physiol. 2006 Mar;290(3):F710-9. Epub 2005 Sep 27.
Ref 537617Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patients with hypertension. J Renin Angiotensin Aldosterone Syst. 2009 Jul 17.
Ref 537925Comparative effects of three different potent renin inhibitors in primates. Hypertension. 1993 Jul;22(1):9-17.
Ref 543623(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2413).
Ref 544476New Developments in the Pharmacological Treatment of Hypertension: Dead-End or a Glimmer at the Horizon?. Curr Hypertens Rep. 2015; 17(6): 42.
Ref 545187Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002406)
Ref 546033Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005981)
Ref 546733Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010026)
Ref 549203Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033655)
Ref 551182Aliskiren, a novel oral renin inhibitor, provides dose-dependent efficacy and placebo-like tolerability in Japanese patients with hypertension. Hypertension Research (2006) 29, 997-1005. doi:10.1291/hypres.29.997
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551397Liver disease associated with occupational exposure to the solvent dimethylformamide. Ann Intern Med. 1988 May;108(5):680-6.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 1572605The ChEMBL database in 2017.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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