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

General Information of Drug (ID: DMTL94F)

• Drug Name: Maraviroc Drug Info
• Synonyms: 376348-65-1; Selzentry; Celsentri; UK-427857; UK-427,857; UK 427857; UNII-MD6P741W8A; MD6P741W8A; CHEMBL256907; MVC; CHEMBL1201187; CHEBI:63608; 4,4-difluoro-N-[(1S)-3-[(1R,5S)-3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[321]octan-8-yl]-1-phenylpropyl]cyclohexane-1-carboxamide; Isopropyl, 4,4-difluoro-N-((1S)-3-{(1R,3s,5S)-3-(3-methyl-5-(propan-2-yl)-4H-1,2,4-triazol-4-yl)-8-azabicyclo(321)octan-8-yl}-1-phenylpropyl)cyclohexanecarboxamide; Maraviroc [USAN]; Celsentri (TN); Celsentri(TM); PRO 140 & Maraviroc; Selzentry (TN); Selzentry(TM); UK-427,857 maraviroc (MVC); Exo-4,4-Difluoro-N-[3-[3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[321]oct-8-yl]-1(S)-phenylpropyl]cyclohexanecarboxamide; PRO 140 (Anti-CCR5 monoclonal antibody) & exo-4,4-Difluoro-N-[3-[3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[321]oct-8-yl]-1(S)-phenylpropyl]cyclohexanecarboxamide; 4,4-Difluoro-N-((1S)-3-(exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo(321)oct-8-yl)-1-phenylpropyl)cyclohexanecarboxamide; [3H]maraviroc

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[1]
Chronic obstructive pulmonary disease	CA22	Phase 3	[1]

• Therapeutic Class: Anti-HIV Agents
• Cross-matching ID:
  PubChem CID: 3002977
  ChEBI ID: CHEBI:63608
  CAS Number: CAS 376348-65-1
  TTD Drug ID: DMTL94F
  VARIDT Drug ID: DR00730
  ACDINA Drug ID: D00384

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vicriviroc	DMMTW9K	Human immunodeficiency virus infection	1C62	Phase 3	[5]
PRO-140	DMD1FTP	Human immunodeficiency virus infection	1C62	Phase 3	[6]
E-913	DMUHS5Q	Human immunodeficiency virus infection	1C62	Phase 3	[7]
PRO 140	DMCGK6X	Human immunodeficiency virus-1 infection	1C62	Phase 2/3	[8]
INCB9471	DMMWC6F	Infectious disease	1A00-CA43.1	Phase 2a	[7]
Cenicriviroc	DM4V8WF	Human immunodeficiency virus infection	1C62	Phase 2	[9]
BMS-813160	DMKY638	Diabetic nephropathy	GB61.Z	Phase 2	[10]
SB-728-T	DMRWE5D	Human immunodeficiency virus infection	1C62	Phase 2	[11]
PF-232798	DM8T6KQ	Human immunodeficiency virus infection	1C62	Phase 2	[12]
GSK-706769	DMPLKAH	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
DdRNAi therapy rHIV7-shl-TAR-CCR5RZ, stem cells	DM0I5LM	Human immunodeficiency virus infection	1C62	Phase 1/2	[14]
SCH-C	DM8J9SF	Human immunodeficiency virus infection	1C62	Discontinued in Phase 1	[15]
viral macrophage inflammatory protein-II	DMAXOPS	Discovery agent	N.A.	Investigative	[16]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[17]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[18]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[19]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[20]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[19]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[19]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[21]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[19]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[22]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]

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	Antagonist	[2]
CCR5 messenger RNA (CCR5 mRNA)	TTJIH8Q	CCR5_HUMAN	Antagonist	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[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: 806).
• [2] Rapamycin enhances aplaviroc anti-HIV activity: implications for the clinical development of novel CCR5 antagonists. Antiviral Res. 2009 Jul;83(1):86-9.
• [3] 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.
• [4] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [5] HIV entry: new insights and implications for patient management. Curr Opin Infect Dis. 2009 Feb;22(1):35-42.
• [6] 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.
• [7] Species selectivity of small-molecular antagonists for the CCR5 chemokine receptor. Int Immunopharmacol. 2007 Dec 5;7(12):1528-34.
• [8] The return of PRO 140, a CCR5-directed mAb. Curr Opin HIV AIDS. 2018 Jul;13(4):346-353.
• [9] 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.
• [10] A dual CCR2/CCR5 chemokine antagonist, BMS-813160. Expert Opin Ther Pat. 2011 Dec;21(12):1919-24.
• [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] Progress on RNAi-based molecular medicines. Int J Nanomedicine. 2012; 7: 3971-3980.
• [15] 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.
• [16] A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus. Science. 1997 Sep 12;277(5332):1656-9.
• [17] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [18] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [19] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [20] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [21] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [22] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [23] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.