Details of the Drug

General Information of Drug (ID: DMKY638)

• Drug Name: BMS-813160
• Synonyms: BMS-585059; CCR2/CCR5 chemokine antagonist (immune disorders, cardiovascular disorders), BMS; CCR2/CCR5 dual antagonist (cardiovascular disease), Bristol-Myers Squibb; CCR2/CCR5 dual antagonist (immunology), Bristol-Myers Squibb

Indication

Disease Entry	ICD 11	Status	REF
Diabetic nephropathy	GB61.Z	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 484.6
  Topological Polar Surface Area (xlogp); 2.7
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C25H40N8O2
  IUPAC Name: N-[(1R,2S,5R)-5-(tert-butylamino)-2-[(3S)-3-[(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-yl)amino]-2-oxopyrrolidin-1-yl]cyclohexyl]acetamide
  Canonical SMILES: CC(=O)N[C@@H]1C[C@@H](CC[C@@H]1N2CC[C@@H](C2=O)NC3=NC=NC4=CC(=NN43)C(C)(C)C)NC(C)(C)C
  InChI: InChI=1S/C25H40N8O2/c1-15(34)28-18-12-16(30-25(5,6)7)8-9-19(18)32-11-10-17(22(32)35)29-23-27-14-26-21-13-20(24(2,3)4)31-33(21)23/h13-14,16-19,30H,8-12H2,1-7H3,(H,28,34)(H,26,27,29)/t16-,17+,18-,19+/m1/s1
  InChIKey: CMVHFGNTABZQJU-HCXYKTFWSA-N
• Cross-matching ID:
  PubChem CID: 51039119
  CAS Number: 1286279-29-5
  DrugBank ID: DB16240
  TTD ID: D0B1SG

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
C-C chemokine receptor type 2 (CCR2)	TTFZYTO	CCR2_HUMAN	Modulator	[3], [4]
C-C chemokine receptor type 5 (CCR5)	TT2CEJG	CCR5_HUMAN	Modulator	[3], [4]

References

• [1] ClinicalTrials.gov (NCT01752985) Study to Evaluate the Effects of BMS-813160 on Protein Loss in the Urine of Subjects With Type 2 Diabetes and Diabetic Kidney Disease. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] A dual CCR2/CCR5 chemokine antagonist, BMS-813160. Expert Opin Ther Pat. 2011 Dec;21(12):1919-24.
• [4] Methods for improving thymic recovery and preventing and treating graft versus host disease using ccr2 and ccr5 antagonists
• [5] Rapamycin enhances aplaviroc anti-HIV activity: implications for the clinical development of novel CCR5 antagonists. Antiviral Res. 2009 Jul;83(1):86-9.
• [6] HIV entry: new insights and implications for patient management. Curr Opin Infect Dis. 2009 Feb;22(1):35-42.
• [7] Agonist-induced internalization of CC chemokine receptor 5 as a mechanism to inhibit HIV replication. J Pharmacol Exp Ther. 2011 Jun;337(3):655-62.
• [8] Species selectivity of small-molecular antagonists for the CCR5 chemokine receptor. Int Immunopharmacol. 2007 Dec 5;7(12):1528-34.
• [9] The return of PRO 140, a CCR5-directed mAb. Curr Opin HIV AIDS. 2018 Jul;13(4):346-353.
• [10] The dual CCR5 and CCR2 inhibitor cenicriviroc does not redistribute HIV into extracellular space: implications for plasma viral load and intracellular DNA decline. J Antimicrob Chemother. 2015 Mar;70(3):750-6.
• [11] Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV. N Engl J Med. 2014 March 6; 370(10): 901-910.
• [12] An imidazopiperidine series of CCR5 antagonists for the treatment of HIV: the discovery of N-{(1S)-1-(3-fluorophenyl)-3-[(3-endo)-3-(5-isobutyryl-2-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]propyl}acetamide (PF-232798). J Med Chem. 2011 Jan 13;54(1):67-77.
• [13] Tapping into combination pills for HIV. Nat Rev Drug Discov. 2009 Jun;8(6):439-40.
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [16] Present and future in the treatment of diabetic kidney disease. J Diabetes Res. 2015;2015:801348.
• [17] CA patent application no. 841416, Method of selecting therapeutic indications.
• [18] Therapeutic use of a clinical stage CCR2 inhibitor, CCX872, in obesity-associated steatohepatitis. The Lancet Volume 383, Supplement 1, 26 February 2014, Pages S78.
• [19] Assessment of chemokine receptor function on monocytes in whole blood: In vitro and ex vivo evaluations of a CCR2 antagonist. J Immunol Methods. 2010 Jan 31;352(1-2):101-10.
• [20] Incyte Announces Second Quarter 2005 Financial Results; Reports Positive Phase IIb Results for Reverset in Treatment-Experienced HIV Patients. Incyte Corporation. 2005.
• [21] Selective CCR2-targeted macrophage depletion ameliorates experimental mesangioproliferative glomerulonephritis. Clin Exp Immunol. 2009 February; 155(2): 295-303.
• [22] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)