Target Information
Target General Information | Top | |||||
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Target ID |
T61622
(Former ID: TTDS00451)
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Target Name |
Angiotensinogenase renin (REN)
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Synonyms |
Renin; Angiotensinogenase
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Gene Name |
REN
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Hypertension [ICD-11: BA00-BA04] | |||||
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.
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BioChemical Class |
Peptidase
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UniProt ID | ||||||
EC Number |
EC 3.4.23.15
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Sequence |
MDGWRRMPRWGLLLLLWGSCTFGLPTDTTTFKRIFLKRMPSIRESLKERGVDMARLGPEW
SQPMKRLTLGNTTSSVILTNYMDTQYYGEIGIGTPPQTFKVVFDTGSSNVWVPSSKCSRL YTACVYHKLFDASDSSSYKHNGTELTLRYSTGTVSGFLSQDIITVGGITVTQMFGEVTEM PALPFMLAEFDGVVGMGFIEQAIGRVTPIFDNIISQGVLKEDVFSFYYNRDSENSQSLGG QIVLGGSDPQHYEGNFHYINLIKTGVWQIQMKGVSVGSSTLLCEDGCLALVDTGASYISG STSSIEKLMEALGAKKRLFDYVVKCNEGPTLPDISFHLGGKEYTLTSADYVFQESYSSKK LCTLAIHAMDIPPPTGPTWALGATFIRKFYTEFDRRNNRIGFALAR Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
ADReCS ID | BADD_A02216 ; BADD_A05470 | |||||
HIT2.0 ID | T82P0Z |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
1 | Aliskiren | Drug Info | Approved | Hypertension | [2], [3], [4] | |
2 | Remikiren | Drug Info | Approved | Hypertension | [5] | |
Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
1 | CP-80794 | Drug Info | Phase 2 | Hypertension | [6] | |
2 | SPP-600 | Drug Info | Phase 2 | Hypertension | [7] | |
3 | SR-43845 | Drug Info | Phase 2 | Glaucoma/ocular hypertension | [8] | |
4 | TAK-272 | Drug Info | Phase 2 | Type-2 diabetes | [9] | |
5 | ACT-178882 | Drug Info | Phase 1 | Cardiovascular disease | [10] | |
6 | CARD-024 | Drug Info | Phase 1 | Cardiovascular disease | [11] | |
7 | VTP-27999 | Drug Info | Phase 1 | Hypertension | [12] | |
Discontinued Drug(s) | [+] 15 Discontinued Drugs | + | ||||
1 | Enalkiren | Drug Info | Discontinued in Phase 2 | Glaucoma/ocular hypertension | [13] | |
2 | FK-906 | Drug Info | Discontinued in Phase 2 | Hypertension | [14] | |
3 | ZANKIREN | Drug Info | Discontinued in Phase 2 | Hypertension | [15] | |
4 | RS-8891 | Drug Info | Discontinued in Phase 1 | Hypertension | [16] | |
5 | SPP-1148 | Drug Info | Discontinued in Phase 1 | Hypertension | [17] | |
6 | SPP-676 | Drug Info | Discontinued in Phase 1 | Hypertension | [18] | |
7 | A-74273 | Drug Info | Terminated | Hypertension | [19] | |
8 | BILA-2157BS | Drug Info | Terminated | Hypertension | [20] | |
9 | Ciprokiren | Drug Info | Terminated | Hypertension | [21] | |
10 | ES-1005 | Drug Info | Terminated | Hypertension | [22] | |
11 | JTP-2724 | Drug Info | Terminated | Hypertension | [23] | |
12 | JTP-4761 | Drug Info | Terminated | Hypertension | [24] | |
13 | KRI-1314 | Drug Info | Terminated | Hypertension | [25] | |
14 | SC-56525 | Drug Info | Terminated | Hypertension | [26] | |
15 | SQ-33800 | Drug Info | Terminated | Hypertension | [27] | |
Mode of Action | [+] 3 Modes of Action | + | ||||
Inhibitor | [+] 48 Inhibitor drugs | + | ||||
1 | Aliskiren | Drug Info | [1] | |||
2 | Remikiren | Drug Info | [5] | |||
3 | CP-80794 | Drug Info | [28] | |||
4 | SPP-600 | Drug Info | [29] | |||
5 | SR-43845 | Drug Info | [30], [31] | |||
6 | ACT-178882 | Drug Info | [33] | |||
7 | VTP-27999 | Drug Info | [35] | |||
8 | Enalkiren | Drug Info | [36] | |||
9 | FK-906 | Drug Info | [37] | |||
10 | ZANKIREN | Drug Info | [38] | |||
11 | RS-8891 | Drug Info | [39] | |||
12 | SPP-1148 | Drug Info | [35] | |||
13 | SPP-676 | Drug Info | [35] | |||
14 | A-74273 | Drug Info | [40] | |||
15 | BILA-2157BS | Drug Info | [41] | |||
16 | Ciprokiren | Drug Info | [42] | |||
17 | ES-1005 | Drug Info | [43] | |||
18 | JTP-2724 | Drug Info | [44] | |||
19 | JTP-4761 | Drug Info | [45] | |||
20 | KRI-1314 | Drug Info | [46] | |||
21 | SC-56525 | Drug Info | [47] | |||
22 | SQ-33800 | Drug Info | [48] | |||
23 | (H-261)Boc-His-Pro-Phe-His-Leu(OH)-Val-Ile-His-OH | Drug Info | [49] | |||
24 | 1-Hydroxy-2-Amino-3-Cyclohexylpropane | Drug Info | [50] | |||
25 | 1-Hydroxy-3-Methylbutane | Drug Info | [50] | |||
26 | 1-Methyl-2-Oxy-5,5-Dimethyl Pyrrolidine | Drug Info | [50] | |||
27 | 2-Cyclopropylmethylenepropanal | Drug Info | [50] | |||
28 | 2-Methyl-3-(2-Aminothiazolo)Propanal | Drug Info | [51] | |||
29 | 3-Phenyl-1,2-Propandiol | Drug Info | [50] | |||
30 | CP-305202 | Drug Info | [52] | |||
31 | Dimethylformamide | Drug Info | [53] | |||
32 | ES-6864 | Drug Info | [31], [54] | |||
33 | Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro | Drug Info | [55] | |||
34 | Iva-His-Pro-Phe-His-ACHPA-Leu-Phe-NH2 | Drug Info | [56] | |||
35 | Iva-His-Pro-Phe-His-AHPPA-Leu-Phe-NH2 | Drug Info | [56] | |||
36 | Iva-His-Pro-Phe-His-Sta-Leu-Phe-NH2 | Drug Info | [56] | |||
37 | N-Methyl-N-(Methylbenzyl)Formamide | Drug Info | [51] | |||
38 | PP1-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O) | Drug Info | [58] | |||
39 | PP2-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O) | Drug Info | [58] | |||
40 | Pro-His-Pro-His-Leu-Phe-Val-Tyr | Drug Info | [55] | |||
41 | Pro-His-Pro-His-Phe-Phe-Val-Tyr | Drug Info | [55] | |||
42 | Pro-His-Pro-His-Phe-Phe-Val-Tyr-Lys | Drug Info | [55] | |||
43 | Pro-His-Pro-Phe-His-Leu(CH2NH)Val-Ile-His-Lys | Drug Info | [59] | |||
44 | Ro-65-7219 | Drug Info | [52] | |||
45 | Ro-66-1168 | Drug Info | [38] | |||
46 | SPP-800 | Drug Info | [34] | |||
47 | Sul-Pro-Phe-N-MeHis-LVA-Ile-Amp | Drug Info | [58] | |||
48 | Sul-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O) | Drug Info | [58] | |||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | TAK-272 | Drug Info | [32] | |||
2 | JT-2724 | Drug Info | [57] | |||
Agonist | [+] 1 Agonist drugs | + | ||||
1 | CARD-024 | Drug Info | [34] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Renin-angiotensin system | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Angiotensin Metabolism | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Metabolism of Angiotensinogen to Angiotensins | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | ACE Inhibitor Pathway | |||||
2 | Metabolism of Angiotensinogen to Angiotensins |
Target-Related Models and Studies | Top | |||||
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Target Validation | ||||||
Target QSAR Model |
References | Top | |||||
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REF 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. | |||||
REF 2 | 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. (Ligand id: 4812). | |||||
REF 3 | 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9. | |||||
REF 4 | Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63. | |||||
REF 5 | Functional expression of the renin-angiotensin system in human podocytes. Am J Physiol Renal Physiol. 2006 Mar;290(3):F710-9. | |||||
REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001570) | |||||
REF 7 | ClinicalTrials.gov (NCT00376636) Phase IIa Safety and Efficacy Study of SPP635 in Mild to Moderate Hypertension. U.S. National Institutes of Health. | |||||
REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001290) | |||||
REF 9 | ClinicalTrials.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 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029409) | |||||
REF 11 | ClinicalTrials.gov (NCT01757860) Safety and Pharmacokinetics Study of CARD-024 in Healthy Subjects. U.S. National Institutes of Health. | |||||
REF 12 | ClinicalTrials.gov (NCT01217736) Direct Renin Inhibition and the Kidney. U.S. National Institutes of Health. | |||||
REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000369) | |||||
REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001939) | |||||
REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002065) | |||||
REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000425) | |||||
REF 17 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025565) | |||||
REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027192) | |||||
REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001791) | |||||
REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006753) | |||||
REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005529) | |||||
REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002295) | |||||
REF 23 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010164) | |||||
REF 24 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005981) | |||||
REF 25 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002396) | |||||
REF 26 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004067) | |||||
REF 27 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002406) | |||||
REF 28 | 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. | |||||
REF 29 | Effect of SPP 635, a renin inhibitor, on intraocular pressure in glaucomatous monkey eyes. Exp Eye Res. 2012 Jan;94(1):146-9. | |||||
REF 30 | 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. | |||||
REF 31 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 32 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033655) | |||||
REF 33 | 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. | |||||
REF 34 | 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). | |||||
REF 35 | New Developments in the Pharmacological Treatment of Hypertension: Dead-End or a Glimmer at the Horizon . Curr Hypertens Rep. 2015; 17(6): 42. | |||||
REF 36 | Comparative effects of three different potent renin inhibitors in primates. Hypertension. 1993 Jul;22(1):9-17. | |||||
REF 37 | Antihypertensive efficacy of FK906, a novel human renin inhibitor. Clin Ther. 1993 May-Jun;15(3):539-48. | |||||
REF 38 | Design and preparation of potent, nonpeptidic, bioavailable renin inhibitors. J Med Chem. 2009 Jun 25;52(12):3689-702. | |||||
REF 39 | 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 | |||||
REF 40 | 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. | |||||
REF 41 | 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. | |||||
REF 42 | Ciprokiren (Ro 44-9375). A renin inhibitor with increasing effects on chronic treatment. Hypertension. 1994 Aug;24(2):163-9. | |||||
REF 43 | 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. | |||||
REF 44 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010026) | |||||
REF 45 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005981) | |||||
REF 46 | KRI-1314: an orally effective inhibitor of human renin. Jpn J Pharmacol. 1993 Sep;63(1):109-19. | |||||
REF 47 | Effects of SC-56525, a potent, orally active renin inhibitor, in salt-depleted and renal hypertensive dogs. Hypertension. 1995 Jul;26(1):95-100. | |||||
REF 48 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002406) | |||||
REF 49 | Renin inhibitors. Dipeptide analogues of angiotensinogen incorporating transition-state, nonpeptidic replacements at the scissile bond. J Med Chem. 1987 Oct;30(10):1729-37. | |||||
REF 50 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 51 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 52 | Direct renin inhibitors as a new therapy for hypertension. J Med Chem. 2010 Nov 11;53(21):7490-520. | |||||
REF 53 | Liver disease associated with occupational exposure to the solvent dimethylformamide. Ann Intern Med. 1988 May;108(5):680-6. | |||||
REF 54 | A highly potent and long-acting oral inhibitor of human renin. Hypertension. 1988 Jun;11(6 Pt 2):708-12. | |||||
REF 55 | Inhibition of the renin-angiotensin system. A new approach to the therapy of hypertension. J Med Chem. 1981 Apr;24(4):355-61. | |||||
REF 56 | 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. | |||||
REF 57 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. | |||||
REF 58 | 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. | |||||
REF 59 | Synthesis and biological activity of some transition-state inhibitors of human renin. J Med Chem. 1988 Sep;31(9):1839-46. |
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