General Information of Drug (ID: DM4V8WF)

Drug Name
Cenicriviroc
Synonyms
Cenicriviroc; 497223-25-3; TBR-652; TAK-652; Cenicriviroc mesylate; UNII-15C116UA4Y; TAK652; 15C116UA4Y; TBR652; Cenicriviroc (USAN/INN); SCHEMBL3157768; SCHEMBL3157748; CHEMBL2110727; MolPort-044-723-655; MolPort-044-649-359; EX-A1608; BDBM50422828; AKOS027250788; CS-6148; DB11758; SB16976; HY-14882; AS-35184; D09878; UNII-15C116UA4Y component PNDKCRDVVKJPKG-WHERJAGFSA-N; 1-Benzazocine-5-carboxamide, 8-[4-(2-butoxyethoxy)phenyl]-1,2,3,4-tetrahydro-1-(2-methylpropyl)-N-[4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]phenyl]-, (5E)-
Indication
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Phase 2 [1], [2]
Human immunodeficiency virus-1 infection 1C62 Phase 2 [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 696.9
Topological Polar Surface Area (xlogp) 7.5
Rotatable Bond Count (rotbonds) 17
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 7
Chemical Identifiers
Formula
C41H52N4O4S
IUPAC Name
(5E)-8-[4-(2-butoxyethoxy)phenyl]-1-(2-methylpropyl)-N-[4-[(S)-(3-propylimidazol-4-yl)methylsulfinyl]phenyl]-3,4-dihydro-2H-1-benzazocine-5-carboxamide
Canonical SMILES
CCCCOCCOC1=CC=C(C=C1)C2=CC/3=C(C=C2)N(CCC/C(=C3)/C(=O)NC4=CC=C(C=C4)[S@@](=O)CC5=CN=CN5CCC)CC(C)C
InChI
InChI=1S/C41H52N4O4S/c1-5-7-22-48-23-24-49-38-15-10-32(11-16-38)33-12-19-40-35(25-33)26-34(9-8-21-44(40)28-31(3)4)41(46)43-36-13-17-39(18-14-36)50(47)29-37-27-42-30-45(37)20-6-2/h10-19,25-27,30-31H,5-9,20-24,28-29H2,1-4H3,(H,43,46)/b34-26+/t50-/m0/s1
InChIKey
PNDKCRDVVKJPKG-WHERJAGFSA-N
Cross-matching ID
PubChem CID
11285792
ChEBI ID
CHEBI:149636
CAS Number
497223-25-3
DrugBank ID
DB11758
TTD ID
D0YQ7U
INTEDE ID
DR1848

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 Antagonist [3]
C-C chemokine receptor type 5 (CCR5) TT2CEJG CCR5_HUMAN Modulator [2]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [4]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Human immunodeficiency virus infection
ICD Disease Classification 1C62
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 9.78E-01 -3.38E-03 -5.71E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 9.85E-01 2.24E-02 7.33E-02
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 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: 801).
2 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.
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Pharmacokinetics, safety, and CCR2/CCR5 antagonist activity of cenicriviroc in participants with mild or moderate hepatic impairment. Clin Transl Sci. 2016 Jun;9(3):139-48.
5 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
6 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
7 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
8 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
9 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
10 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
11 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
12 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
13 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
14 Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
15 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
16 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
17 Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
18 Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
19 Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
20 PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
21 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
22 Rapamycin enhances aplaviroc anti-HIV activity: implications for the clinical development of novel CCR5 antagonists. Antiviral Res. 2009 Jul;83(1):86-9.
23 HIV entry: new insights and implications for patient management. Curr Opin Infect Dis. 2009 Feb;22(1):35-42.
24 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.
25 Species selectivity of small-molecular antagonists for the CCR5 chemokine receptor. Int Immunopharmacol. 2007 Dec 5;7(12):1528-34.
26 The return of PRO 140, a CCR5-directed mAb. Curr Opin HIV AIDS. 2018 Jul;13(4):346-353.
27 A dual CCR2/CCR5 chemokine antagonist, BMS-813160. Expert Opin Ther Pat. 2011 Dec;21(12):1919-24.
28 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.
29 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.
30 Tapping into combination pills for HIV. Nat Rev Drug Discov. 2009 Jun;8(6):439-40.
31 Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
32 Present and future in the treatment of diabetic kidney disease. J Diabetes Res. 2015;2015:801348.
33 CA patent application no. 841416, Method of selecting therapeutic indications.
34 Therapeutic use of a clinical stage CCR2 inhibitor, CCX872, in obesity-associated steatohepatitis. The Lancet Volume 383, Supplement 1, 26 February 2014, Pages S78.
35 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.
36 Incyte Announces Second Quarter 2005 Financial Results; Reports Positive Phase IIb Results for Reverset in Treatment-Experienced HIV Patients. Incyte Corporation. 2005.
37 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
38 Selective CCR2-targeted macrophage depletion ameliorates experimental mesangioproliferative glomerulonephritis. Clin Exp Immunol. 2009 February; 155(2): 295-303.
39 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)