General Information of Drug Therapeutic Target (DTT) (ID: TTB2MXP)

DTT Name Angiotensinogenase renin (REN)
Synonyms Renin; Angiotensinogenase
Gene Name REN
DTT Type
Successful target
[1]
BioChemical Class
Peptidase
UniProt ID
RENI_HUMAN
TTD ID
T61622
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.4.23.15
Sequence
MDGWRRMPRWGLLLLLWGSCTFGLPTDTTTFKRIFLKRMPSIRESLKERGVDMARLGPEW
SQPMKRLTLGNTTSSVILTNYMDTQYYGEIGIGTPPQTFKVVFDTGSSNVWVPSSKCSRL
YTACVYHKLFDASDSSSYKHNGTELTLRYSTGTVSGFLSQDIITVGGITVTQMFGEVTEM
PALPFMLAEFDGVVGMGFIEQAIGRVTPIFDNIISQGVLKEDVFSFYYNRDSENSQSLGG
QIVLGGSDPQHYEGNFHYINLIKTGVWQIQMKGVSVGSSTLLCEDGCLALVDTGASYISG
STSSIEKLMEALGAKKRLFDYVVKCNEGPTLPDISFHLGGKEYTLTSADYVFQESYSSKK
LCTLAIHAMDIPPPTGPTWALGATFIRKFYTEFDRRNNRIGFALAR
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.
KEGG Pathway
Renin-angiotensin system (hsa04614 )
Reactome Pathway
Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Aliskiren DM1BV7W Hypertension BA00-BA04 Approved [1]
Remikiren DMNAKLY Hypertension BA00-BA04 Approved [2]
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8 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CP-80794 DMT3ORQ Hypertension BA00-BA04 Phase 2 [3]
SPH3127 DMYL6RA Ulcerative colitis DD71 Phase 2 [4]
SPP-600 DMOVQP8 Hypertension BA00-BA04 Phase 2 [5]
SR-43845 DMTOCIV Glaucoma/ocular hypertension 9C61 Phase 2 [6]
TAK-272 DM81UAZ Type-2 diabetes 5A11 Phase 2 [7]
ACT-178882 DMOZ3AT Cardiovascular disease BA00-BE2Z Phase 1 [8]
CARD-024 DM4SNK8 Cardiovascular disease BA00-BE2Z Phase 1 [9]
VTP-27999 DMQEOD6 Hypertension BA00-BA04 Phase 1 [10]
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⏷ Show the Full List of 8 Clinical Trial Drug(s)
15 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Enalkiren DMDAS5B Glaucoma/ocular hypertension 9C61 Discontinued in Phase 2 [11]
FK-906 DMTEW80 Hypertension BA00-BA04 Discontinued in Phase 2 [12]
ZANKIREN DM9F650 Hypertension BA00-BA04 Discontinued in Phase 2 [13]
RS-8891 DM4P5WO Hypertension BA00-BA04 Discontinued in Phase 1 [14]
SPP-1148 DMWQKEN Hypertension BA00-BA04 Discontinued in Phase 1 [10]
SPP-676 DMKEHGT Hypertension BA00-BA04 Discontinued in Phase 1 [10]
A-74273 DMBEIFL Hypertension BA00-BA04 Terminated [15]
BILA-2157BS DMRV4UL Hypertension BA00-BA04 Terminated [16]
Ciprokiren DM0NJMG Hypertension BA00-BA04 Terminated [17]
ES-1005 DMRP7BX Hypertension BA00-BA04 Terminated [18]
JTP-2724 DMG7B61 Hypertension BA00-BA04 Terminated [19]
JTP-4761 DM6TXKR Hypertension BA00-BA04 Terminated [20]
KRI-1314 DM4QHNG Hypertension BA00-BA04 Terminated [21]
SC-56525 DM25MUA Hypertension BA00-BA04 Terminated [22]
SQ-33800 DMMRWKP Hypertension BA00-BA04 Terminated [23]
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⏷ Show the Full List of 15 Discontinued Drug(s)
27 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(H-261)Boc-His-Pro-Phe-His-Leu(OH)-Val-Ile-His-OH DMVKJ0H Discovery agent N.A. Investigative [24]
1-Hydroxy-2-Amino-3-Cyclohexylpropane DM9EWN8 Discovery agent N.A. Investigative [25]
1-Hydroxy-3-Methylbutane DMZ8IL9 Discovery agent N.A. Investigative [25]
1-Methyl-2-Oxy-5,5-Dimethyl Pyrrolidine DM5GELS Discovery agent N.A. Investigative [25]
2-Cyclopropylmethylenepropanal DM0W2QB Discovery agent N.A. Investigative [25]
2-Methyl-3-(2-Aminothiazolo)Propanal DM3DNFQ Discovery agent N.A. Investigative [26]
3-Phenyl-1,2-Propandiol DMU9WGT Discovery agent N.A. Investigative [25]
CP-305202 DMME6K2 Discovery agent N.A. Investigative [27]
Dimethylformamide DML6O4N Discovery agent N.A. Investigative [28]
ES-6864 DMSNM5O Hypertension BA00-BA04 Investigative [29]
Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro DM1Q83B Discovery agent N.A. Investigative [30]
Iva-His-Pro-Phe-His-ACHPA-Leu-Phe-NH2 DMFMYIH Discovery agent N.A. Investigative [31]
Iva-His-Pro-Phe-His-AHPPA-Leu-Phe-NH2 DMZTIU3 Discovery agent N.A. Investigative [31]
Iva-His-Pro-Phe-His-Sta-Leu-Phe-NH2 DM92QIW Discovery agent N.A. Investigative [31]
JT-2724 DMD9W0B Discovery agent N.A. Investigative [32]
N-Methyl-N-(Methylbenzyl)Formamide DMYPEX3 Discovery agent N.A. Investigative [26]
PP1-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O) DMYA5CB Discovery agent N.A. Investigative [33]
PP2-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O) DM3NUKX Discovery agent N.A. Investigative [33]
Pro-His-Pro-His-Leu-Phe-Val-Tyr DMZH0KY Discovery agent N.A. Investigative [30]
Pro-His-Pro-His-Phe-Phe-Val-Tyr DMD3WVO Discovery agent N.A. Investigative [30]
Pro-His-Pro-His-Phe-Phe-Val-Tyr-Lys DMNDUI3 Discovery agent N.A. Investigative [30]
Pro-His-Pro-Phe-His-Leu(CH2NH)Val-Ile-His-Lys DM26VFX Discovery agent N.A. Investigative [34]
Ro-65-7219 DM6S742 Discovery agent N.A. Investigative [27]
Ro-66-1168 DMPT01J Discovery agent N.A. Investigative [13]
SPP-800 DMP5VN2 Hypertension BA00-BA04 Investigative [9]
Sul-Pro-Phe-N-MeHis-LVA-Ile-Amp DMTEU0L Discovery agent N.A. Investigative [33]
Sul-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O) DMQB2CN Discovery agent N.A. Investigative [33]
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⏷ Show the Full List of 27 Investigative Drug(s)

References

1 Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patie... J Renin Angiotensin Aldosterone Syst. 2009 Sep;10(3):157-67.
2 Functional expression of the renin-angiotensin system in human podocytes. Am J Physiol Renal Physiol. 2006 Mar;290(3):F710-9.
3 Synergistic 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.
4 Discovery of SPH3127: A Novel, Highly Potent, and Orally Active Direct Renin Inhibitor. J Med Chem. 2022 Aug 25;65(16):10882-10897.
5 Effect of SPP 635, a renin inhibitor, on intraocular pressure in glaucomatous monkey eyes. Exp Eye Res. 2012 Jan;94(1):146-9.
6 Effects 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.
7 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033655)
8 Drug-drug interaction study of ACT-178882, a new renin inhibitor, and diltiazem in healthy subjects. Clin Drug Investig. 2013 Mar;33(3):207-13.
9 URL: 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).
10 New Developments in the Pharmacological Treatment of Hypertension: Dead-End or a Glimmer at the Horizon . Curr Hypertens Rep. 2015; 17(6): 42.
11 Comparative effects of three different potent renin inhibitors in primates. Hypertension. 1993 Jul;22(1):9-17.
12 Antihypertensive efficacy of FK906, a novel human renin inhibitor. Clin Ther. 1993 May-Jun;15(3):539-48.
13 Design and preparation of potent, nonpeptidic, bioavailable renin inhibitors. J Med Chem. 2009 Jun 25;52(12):3689-702.
14 Aliskiren, 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
15 The 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.
16 Comparative studies on differential inhibition of the renin - angiotensin system in the anesthetized guinea pig. Can J Physiol Pharmacol. 1995 Oct;73(10):1512-8.
17 Ciprokiren (Ro 44-9375). A renin inhibitor with increasing effects on chronic treatment. Hypertension. 1994 Aug;24(2):163-9.
18 The 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.
19 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010026)
20 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005981)
21 KRI-1314: an orally effective inhibitor of human renin. Jpn J Pharmacol. 1993 Sep;63(1):109-19.
22 Effects of SC-56525, a potent, orally active renin inhibitor, in salt-depleted and renal hypertensive dogs. Hypertension. 1995 Jul;26(1):95-100.
23 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002406)
24 Renin inhibitors. Dipeptide analogues of angiotensinogen incorporating transition-state, nonpeptidic replacements at the scissile bond. J Med Chem. 1987 Oct;30(10):1729-37.
25 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
26 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
27 Direct renin inhibitors as a new therapy for hypertension. J Med Chem. 2010 Nov 11;53(21):7490-520.
28 Liver disease associated with occupational exposure to the solvent dimethylformamide. Ann Intern Med. 1988 May;108(5):680-6.
29 A highly potent and long-acting oral inhibitor of human renin. Hypertension. 1988 Jun;11(6 Pt 2):708-12.
30 Inhibition of the renin-angiotensin system. A new approach to the therapy of hypertension. J Med Chem. 1981 Apr;24(4):355-61.
31 Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analogue inhibitors containing a novel analogue of statine. J Med Chem. 1985 Dec;28(12):1779-90.
32 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
33 Renin inhibitory peptides. Incorporation of polar, hydrophilic end groups into an active renin inhibitory peptide template and their evaluation in ... J Med Chem. 1991 Feb;34(2):633-42.
34 Synthesis and biological activity of some transition-state inhibitors of human renin. J Med Chem. 1988 Sep;31(9):1839-46.