Target Information

Target General Information

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Target ID

T61622 (Former ID: TTDS00451)

Target Name

Angiotensinogenase renin (REN)

Synonyms

Renin; Angiotensinogenase

Gene Name

REN

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

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

UniProt ID

RENI_HUMAN

EC Number

EC 3.4.23.15

Sequence

MDGWRRMPRWGLLLLLWGSCTFGLPTDTTTFKRIFLKRMPSIRESLKERGVDMARLGPEW
SQPMKRLTLGNTTSSVILTNYMDTQYYGEIGIGTPPQTFKVVFDTGSSNVWVPSSKCSRL
YTACVYHKLFDASDSSSYKHNGTELTLRYSTGTVSGFLSQDIITVGGITVTQMFGEVTEM
PALPFMLAEFDGVVGMGFIEQAIGRVTPIFDNIISQGVLKEDVFSFYYNRDSENSQSLGG
QIVLGGSDPQHYEGNFHYINLIKTGVWQIQMKGVSVGSSTLLCEDGCLALVDTGASYISG
STSSIEKLMEALGAKKRLFDYVVKCNEGPTLPDISFHLGGKEYTLTSADYVFQESYSSKK
LCTLAIHAMDIPPPTGPTWALGATFIRKFYTEFDRRNNRIGFALAR

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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

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Approved Drug(s)

[+] 2 Approved Drugs

Aliskiren

Drug Info

Approved

Hypertension

[2], [3], [4]

Remikiren

Drug Info

Approved

Hypertension

[5]

Clinical Trial Drug(s)

[+] 7 Clinical Trial Drugs

CP-80794

Drug Info

Phase 2

Hypertension

[6]

SPP-600

Drug Info

Phase 2

Hypertension

[7]

SR-43845

Drug Info

Phase 2

Glaucoma/ocular hypertension

[8]

TAK-272

Drug Info

Phase 2

Type-2 diabetes

[9]

ACT-178882

Drug Info

Phase 1

Cardiovascular disease

[10]

CARD-024

Drug Info

Phase 1

Cardiovascular disease

[11]

VTP-27999

Drug Info

Phase 1

Hypertension

[12]

Discontinued Drug(s)

[+] 15 Discontinued Drugs

Enalkiren

Drug Info

Discontinued in Phase 2

Glaucoma/ocular hypertension

[13]

FK-906

Drug Info

Discontinued in Phase 2

Hypertension

[14]

ZANKIREN

Drug Info

Discontinued in Phase 2

Hypertension

[15]

RS-8891

Drug Info

Discontinued in Phase 1

Hypertension

[16]

SPP-1148

Drug Info

Discontinued in Phase 1

Hypertension

[17]

SPP-676

Drug Info

Discontinued in Phase 1

Hypertension

[18]

A-74273

Drug Info

Terminated

Hypertension

[19]

BILA-2157BS

Drug Info

Terminated

Hypertension

[20]

Ciprokiren

Drug Info

Terminated

Hypertension

[21]

ES-1005

Drug Info

Terminated

Hypertension

[22]

JTP-2724

Drug Info

Terminated

Hypertension

[23]

JTP-4761

Drug Info

Terminated

Hypertension

[24]

KRI-1314

Drug Info

Terminated

Hypertension

[25]

SC-56525

Drug Info

Terminated

Hypertension

[26]

SQ-33800

Drug Info

Terminated

Hypertension

[27]

Mode of Action

[+] 3 Modes of Action

Inhibitor

[+] 48 Inhibitor drugs

Aliskiren

Drug Info

[1]

Remikiren

Drug Info

[5]

CP-80794

Drug Info

[28]

SPP-600

Drug Info

[29]

SR-43845

Drug Info

[30], [31]

ACT-178882

Drug Info

[33]

VTP-27999

Drug Info

[35]

Enalkiren

Drug Info

[36]

FK-906

Drug Info

[37]

ZANKIREN

Drug Info

[38]

RS-8891

Drug Info

[39]

SPP-1148

Drug Info

[35]

SPP-676

Drug Info

[35]

A-74273

Drug Info

[40]

BILA-2157BS

Drug Info

[41]

Ciprokiren

Drug Info

[42]

ES-1005

Drug Info

[43]

JTP-2724

Drug Info

[44]

JTP-4761

Drug Info

[45]

KRI-1314

Drug Info

[46]

SC-56525

Drug Info

[47]

SQ-33800

Drug Info

[48]

(H-261)Boc-His-Pro-Phe-His-Leu(OH)-Val-Ile-His-OH

Drug Info

[49]

1-Hydroxy-2-Amino-3-Cyclohexylpropane

Drug Info

[50]

1-Hydroxy-3-Methylbutane

Drug Info

[50]

1-Methyl-2-Oxy-5,5-Dimethyl Pyrrolidine

Drug Info

[50]

2-Cyclopropylmethylenepropanal

Drug Info

[50]

2-Methyl-3-(2-Aminothiazolo)Propanal

Drug Info

[51]

3-Phenyl-1,2-Propandiol

Drug Info

[50]

CP-305202

Drug Info

[52]

Dimethylformamide

Drug Info

[53]

ES-6864

Drug Info

[31], [54]

Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro

Drug Info

[55]

Iva-His-Pro-Phe-His-ACHPA-Leu-Phe-NH2

Drug Info

[56]

Iva-His-Pro-Phe-His-AHPPA-Leu-Phe-NH2

Drug Info

[56]

Iva-His-Pro-Phe-His-Sta-Leu-Phe-NH2

Drug Info

[56]

N-Methyl-N-(Methylbenzyl)Formamide

Drug Info

[51]

PP1-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O)

Drug Info

[58]

PP2-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O)

Drug Info

[58]

Pro-His-Pro-His-Leu-Phe-Val-Tyr

Drug Info

[55]

Pro-His-Pro-His-Phe-Phe-Val-Tyr

Drug Info

[55]

Pro-His-Pro-His-Phe-Phe-Val-Tyr-Lys

Drug Info

[55]

Pro-His-Pro-Phe-His-Leu(CH2NH)Val-Ile-His-Lys

Drug Info

[59]

Ro-65-7219

Drug Info

[52]

Ro-66-1168

Drug Info

[38]

SPP-800

Drug Info

[34]

Sul-Pro-Phe-N-MeHis-LVA-Ile-Amp

Drug Info

[58]

Sul-Pro-Phe-N-MeHis-LVA-Ile-Amp-(O)

Drug Info

[58]

Modulator

[+] 2 Modulator drugs

TAK-272

Drug Info

[32]

JT-2724

Drug Info

[57]

Agonist

[+] 1 Agonist drugs

CARD-024

Drug Info

[34]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"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

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Renin-angiotensin system

Pathwhiz Pathway

[+] 1 Pathwhiz Pathways

Angiotensin Metabolism

Reactome

[+] 1 Reactome Pathways

Metabolism of Angiotensinogen to Angiotensins

WikiPathways

[+] 2 WikiPathways

ACE Inhibitor Pathway

Metabolism of Angiotensinogen to Angiotensins

Target-Related Models and Studies

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Target Validation

Target Validation Info

Target QSAR Model

References

Top

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

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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