Details of the Drug

General Information of Drug (ID: DM9F650)

• Drug Name: ZANKIREN
• Synonyms: Zankiren; UNII-I36B16A34Q; CHEMBL113841; I36B16A34Q; A-72517; Zankiren [INN]; 138742-43-5; A 72517; AC1MJ6K5; SCHEMBL180700; ZINC27084753; BDBM50046798; (S)-N-((1S,2R,3S)-1-(Cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl)-alpha-((alphaS)-alpha-(((4-methyl-1-piperazinyl)sulfonyl)methyl)hydrocinnamamido)-4-thiazolepropionamide; (1S-(1R*(R*(R*)),2S*,3R*))-N-(1-(Cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl)-alpha-((2-(((4-methyl-1-piperazinyl)sulfonyl)methyl)-1-oxo-3-phenylpropyl)amino)-4-thiazolepropanamide

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Discontinued in Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 706
  Topological Polar Surface Area (xlogp); 4.6
  Rotatable Bond Count (rotbonds); 17
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 10
• Chemical Identifiers:
  Formula: C35H55N5O6S2
  IUPAC Name: (2S)-2-benzyl-N-[(2S)-1-[[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]amino]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl]-3-(4-methylpiperazin-1-yl)sulfonylpropanamide
  Canonical SMILES: CC(C)C[C@@H]([C@@H]([C@H](CC1CCCCC1)NC(=O)[C@H](CC2=CSC=N2)NC(=O)[C@H](CC3=CC=CC=C3)CS(=O)(=O)N4CCN(CC4)C)O)O
  InChI: InChI=1S/C35H55N5O6S2/c1-25(2)18-32(41)33(42)30(20-27-12-8-5-9-13-27)37-35(44)31(21-29-22-47-24-36-29)38-34(43)28(19-26-10-6-4-7-11-26)23-48(45,46)40-16-14-39(3)15-17-40/h4,6-7,10-11,22,24-25,27-28,30-33,41-42H,5,8-9,12-21,23H2,1-3H3,(H,37,44)(H,38,43)/t28-,30+,31+,32+,33-/m1/s1
  InChIKey: YFDSDRDMDDGDFC-HOQQKOLYSA-N
• Cross-matching ID:
  PubChem CID: 3086652
  CAS Number: 138742-43-5
  TTD ID: D0J5GT

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiotensinogenase renin (REN)	TTB2MXP	RENI_HUMAN	Inhibitor	[2]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002065)
• [2] Design and preparation of potent, nonpeptidic, bioavailable renin inhibitors. J Med Chem. 2009 Jun 25;52(12):3689-702.
• [3] 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.
• [4] Functional expression of the renin-angiotensin system in human podocytes. Am J Physiol Renal Physiol. 2006 Mar;290(3):F710-9.
• [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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033655)
• [7] 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.
• [8] 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.
• [9] New Developments in the Pharmacological Treatment of Hypertension: Dead-End or a Glimmer at the Horizon . Curr Hypertens Rep. 2015; 17(6): 42.
• [10] 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.
• [11] 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).
• [12] Antihypertensive efficacy of FK906, a novel human renin inhibitor. Clin Ther. 1993 May-Jun;15(3):539-48.