Details of the Drug

General Information of Drug (ID: DM4QHNG)

• Drug Name: KRI-1314
• Synonyms: CHEMBL3350322; Kri-1314; CHEMBL91826; 4-Cyclohexyl-2-hydroxy-3-[3-(1H-imidazol-4-yl)-2-(4-morpholin-4-yl-2-naphthalen-1-ylmethyl-4-oxo-butyrylamino)-propionylamino]-butyric acid isopropyl ester; BDBM50012951; (2R,3S)-3-[N-[(2R)-3-(Morpholinocarbonyl)-2-[(naphthalen-1-yl)methyl]propionyl]-L-histidyl]amino-4-cyclohexyl-2-hydroxybutanoic acid isopropyl ester

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Terminated	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 689.8
  Topological Polar Surface Area (xlogp); 4.5
  Rotatable Bond Count (rotbonds); 16
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C38H51N5O7
  IUPAC Name: propan-2-yl 4-cyclohexyl-2-hydroxy-3-[[(2S)-3-(1H-imidazol-5-yl)-2-[[(2R)-4-morpholin-4-yl-2-(naphthalen-1-ylmethyl)-4-oxobutanoyl]amino]propanoyl]amino]butanoate
  Canonical SMILES: CC(C)OC(=O)C(C(CC1CCCCC1)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC3=CC=CC4=CC=CC=C43)CC(=O)N5CCOCC5)O
  InChI: InChI=1S/C38H51N5O7/c1-25(2)50-38(48)35(45)32(19-26-9-4-3-5-10-26)41-37(47)33(22-30-23-39-24-40-30)42-36(46)29(21-34(44)43-15-17-49-18-16-43)20-28-13-8-12-27-11-6-7-14-31(27)28/h6-8,11-14,23-26,29,32-33,35,45H,3-5,9-10,15-22H2,1-2H3,(H,39,40)(H,41,47)(H,42,46)/t29-,32?,33+,35?/m1/s1
  InChIKey: NQXSBCTYTMQGGJ-GBDGZKRDSA-N
• Cross-matching ID:
  PubChem CID: 5492607
  CAS Number: 128053-53-2
  TTD ID: D0V5XL

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 800002396)
• [2] KRI-1314: an orally effective inhibitor of human renin. Jpn J Pharmacol. 1993 Sep;63(1):109-19.
• [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.