Details of the Drug

General Information of Drug (ID: DMRP7BX)

• Drug Name: ES-1005
• Synonyms: ES 1005; ES-1005; AC1MIZDF; Bis((1-naphthyl)methyl)acetyl-histidyl-statyl-leucyl-episilon-lysinol; 115404-79-0; 1H-Imidazole-4-propanamide, N-(4-((1-(((5-amino-6-hydroxyhexyl)amino)carbonyl)-3-methylbutyl)amino)-2-hydroxy-1-(2-methylpropyl)-4-oxobutyl)-alpha-((3-(1-naphthalenyl)-2-(1-naphthalenylmethyl)-1-oxopropyl)amino)-, dihydrochloride, (1S-(1R*(R*),2R*,4(R*(R*))))-

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 3:
  Molecular Weight; 935
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 25
  Hydrogen Bond Donor Count; 10
  Hydrogen Bond Acceptor Count; 8
• Chemical Identifiers:
  Formula: C50H69Cl2N7O6
  IUPAC Name: (3S)-N-[(2S)-1-[[(5S)-5-amino-6-hydroxyhexyl]amino]-4-methyl-1-oxopentan-2-yl]-3-hydroxy-4-[[3-(1H-imidazol-5-yl)-2-[[3-naphthalen-1-yl-2-(naphthalen-1-ylmethyl)propanoyl]amino]propanoyl]amino]-6-methylheptanamide;dihydrochloride
  Canonical SMILES: CC(C)C[C@@H](C(=O)NCCCC[C@@H](CO)N)NC(=O)C[C@@H](C(CC(C)C)NC(=O)C(CC1=CN=CN1)NC(=O)C(CC2=CC=CC3=CC=CC=C32)CC4=CC=CC5=CC=CC=C54)O.Cl.Cl
  InChI: InChI=1S/C50H67N7O6.2ClH/c1-32(2)23-43(46(59)28-47(60)55-44(24-33(3)4)49(62)53-22-10-9-19-39(51)30-58)56-50(63)45(27-40-29-52-31-54-40)57-48(61)38(25-36-17-11-15-34-13-5-7-20-41(34)36)26-37-18-12-16-35-14-6-8-21-42(35)37;;/h5-8,11-18,20-21,29,31-33,38-39,43-46,58-59H,9-10,19,22-28,30,51H2,1-4H3,(H,52,54)(H,53,62)(H,55,60)(H,56,63)(H,57,61);2*1H/t39-,43?,44-,45?,46-;;/m0../s1
  InChIKey: IYZRFOAPEUBNQP-JPZLKUPGSA-N
• Cross-matching ID:
  PubChem CID: 3082723
  CAS Number: 115404-79-0
  TTD ID: D05FTY

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 800002295)
• [2] 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.
• [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.