Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM8J9SF)

• Drug Name: SCH-C Drug Info
• Synonyms: Ancriviroc; SCH-C & AOP-RANTES; SCH 351125 & SCH 351125 (non-stereospecific); SCH 351125; CHEMBL78535; 305792-46-5; Methanone, (4-bromophenyl)(1'-((2,4-dimethyl-3-pyridinyl)carbonyl)-4'-methyl(1,4'-bipiperidin)-4-yl)-, O-ethyloxime, (Z)-, N1-oxide & Methanone, (4-bromophenyl)(1'-((2,4-dimethyl-3-pyridinyl)carbonyl)-4'-methyl(1,4'-pipiperidin)-4-yl)-, O-ethyloxime, N1-oxide; 1'-[(2,4-Dimethyl-1-oxidopyridin-3-yl)carbonyl]-4'-methyl-1,4'-bipiperidine; Methanone,; Ancriviroc; SCH C; SCH351125; SC-351125; SCH 351125 AOP-RANTES; SCH-351125; SCH-C cpd; AK671/SCH-C; SCH 351125 & AOP-RANTES; SCH-C & PA14; SCH-C AOP-RANTES; SCH-C & AOP-RANTES; Methanone, (4-bromophenyl)[1'-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4'-methyl[1,4'-bipiperidin]-4-yl]-, O-ethyloxime, (Z)-, N1-oxide; Methanone, (4-bromophenyl)[1'-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4'-methyl[1,4'-bipiperidin]-4-yl]-, O-ethyloxime, (Z)-, N1-oxide & AOP-RANTES; Methanone, (4-bromophenyl)[1'-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4'-methyl[1,4'-bipiperidin]-4-yl]-, O-ethyloxime, (Z)-, N1-oxide & PRO 140 (Anti-CCR5 monoclonal antibody); Methanone, (4-bromophenyl)(1'-((2,4-dimethyl-3-pyridinyl)carbonyl)-4'-methyl(1,4'-bipiperidin)-4-yl)-, O-ethyloxime, (Z)-, N1-oxide AOP-RANTES; Methanone, (4-bromophenyl)(1'-((2,4-dimethyl-3-pyridinyl)carbonyl)-4'-methyl(1,4'-bipiperidin)-4-yl)-, O-ethyloxime, (Z)-, N1-oxide & AOP-RANTES; (2,4-Dimethyl-1-oxy-pyridin-3-yl)-(4'-methyl-[1,4']bipiperidinyl-1'-yl)-methanone; 4-((4-bromophenyl)-(ethoxyimino)methyl)-1'-((2,4-dimethyl-3-pyridinyl)carbonyl)-4'-methyl-1,4'-bipiperidine N-oxide; [3H]ancriviroc

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Discontinued in Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 9574343
  CAS Number: CAS 305792-46-5
  TTD Drug ID: DM8J9SF

Molecule-Related Drug Atlas

Drug(s) Targeting C-C chemokine receptor type 5 (CCR5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Maraviroc	DMTL94F	Human immunodeficiency virus infection	1C62	Approved	[5]
Vicriviroc	DMMTW9K	Human immunodeficiency virus infection	1C62	Phase 3	[6]
PRO-140	DMD1FTP	Human immunodeficiency virus infection	1C62	Phase 3	[7]
E-913	DMUHS5Q	Human immunodeficiency virus infection	1C62	Phase 3	[8]
PRO 140	DMCGK6X	Human immunodeficiency virus-1 infection	1C62	Phase 2/3	[9]
INCB9471	DMMWC6F	Infectious disease	1A00-CA43.1	Phase 2a	[8]
Cenicriviroc	DM4V8WF	Human immunodeficiency virus infection	1C62	Phase 2	[10]
BMS-813160	DMKY638	Diabetic nephropathy	GB61.Z	Phase 2	[11]
SB-728-T	DMRWE5D	Human immunodeficiency virus infection	1C62	Phase 2	[12]
PF-232798	DM8T6KQ	Human immunodeficiency virus infection	1C62	Phase 2	[13]

Drug(s) Targeting CCR5 messenger RNA (CCR5 mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Maraviroc	DMTL94F	Human immunodeficiency virus infection	1C62	Approved	[14]
DdRNAi therapy rHIV7-shl-TAR-CCR5RZ, stem cells	DM0I5LM	Human immunodeficiency virus infection	1C62	Phase 1/2	[15]
viral macrophage inflammatory protein-II	DMAXOPS	Discovery agent	N.A.	Investigative	[16]

Drug(s) Affected By Cytochrome P450 2C9 (CYP2C9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[17]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[18]
Dapsone	DM4LT8A	Acne vulgaris	ED80	Approved	[19]
Voriconazole	DMAOL2S	Aspergillosis	1F20	Approved	[20]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[21]
Zafirlukast	DMHNQOG	Asthma	CA23	Approved	[22]
Niclosamide	DMJAGXQ	Cestodes infection	1F70-1F76	Approved	[19]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[23]
Fluconazole	DMOWZ6B	Cryptococcal meningitis		Approved	[20]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[19]

Drug(s) Affected By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Eplerenone	DMF0NQR	Heart failure	BD10-BD13	Approved	[24]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[17]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[25]
Voriconazole	DMAOL2S	Aspergillosis	1F20	Approved	[20]
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[19]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[19]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[26]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[27]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[28]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
C-C chemokine receptor type 5 (CCR5)	TT2CEJG	CCR5_HUMAN	Binder	[2]
CCR5 messenger RNA (CCR5 mRNA)	TTJIH8Q	CCR5_HUMAN	Antagonist	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Biotransformations	[4]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Biotransformations	[4]

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: 804).
• [2] Progress in targeting HIV-1 entry. Drug Discov Today. 2005 Aug 15;10(16):1085-94.
• [3] Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2005 Dec;49(12):4911-9.
• [4] Identification of human liver cytochrome P450 enzymes involved in the metabolism of SCH 351125, a CCR5 antagonist. Xenobiotica. 2005 May;35(5):405-17. doi: 10.1080/00498250500136569.
• [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] A dual CCR2/CCR5 chemokine antagonist, BMS-813160. Expert Opin Ther Pat. 2011 Dec;21(12):1919-24.
• [12] 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.
• [13] 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.
• [14] Molecular cloning and radioligand binding characterization of the chemokine receptor CCR5 from rhesus macaque and human. Biochem Pharmacol. 2005 Dec 19;71(1-2):163-72.
• [15] Progress on RNAi-based molecular medicines. Int J Nanomedicine. 2012; 7: 3971-3980.
• [16] A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus. Science. 1997 Sep 12;277(5332):1656-9.
• [17] Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol. Chem Biol Interact. 2014 May 25;215:62-8.
• [18] Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos. 2003 Apr;31(4):439-46.
• [19] Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
• [20] The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother. 2004 Sep;48(9):3272-8.
• [21] Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res. 2012;14(4):382-95.
• [22] Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes. Xenobiotica. 2004 May;34(5):429-38.
• [23] The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes. Life Sci. 2006 Nov 25;79(26):2432-40.
• [24] The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicol Lett. 2019 Oct 15;315:9-13.
• [25] Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells. Toxicol Sci. 2006 Jul;92(1):51-60.
• [26] Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
• [27] Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
• [28] Studies of the toxicological potential of capsinoids, XIII: inhibitory effects of capsaicin and capsinoids on cytochrome P450 3A4 in human liver microsomes. Int J Toxicol. 2010 Mar;29(2 Suppl):22S-6S.
• [29] Investigation of the effects of axitinib on the pharmacokinetics of loperamide and its main metabolite N-demethylated loperamide in rats by UPLC-MS/MS. Chem Biol Interact. 2019 Sep 1;310:108744. doi: 10.1016/j.cbi.2019.108744. Epub 2019 Jul 9.