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

General Information of Drug (ID: DMT8J0I)

• Drug Name: GSK1265744 Drug Info
• Synonyms: Cabotegravir; 1051375-10-0; GSK1265744; UNII-HMH0132Z1Q; GSK744; GSK1265744A; GSK-1265744; HMH0132Z1Q; Cabotegravir (GSK744, GSK1265744); CAB; Oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide, N-[(2,4-difluorophenyl)methyl]-2,3,5,7,11,11a-hexahydro-6-hydroxy-3-methyl-5,7-dioxo-, (3S,11aR)-;Oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide, N-[(2,4-difluorophenyl)methyl]-2,3,5,7,11,11a-hexahydro-6-hydroxy-3-methyl-5,7-dioxo-, (3S,11aR)-; Cabotegravir [USAN:INN]; GSK744 LAP; GSK744 LA; S/GSK1265744; GSK 744; 744 LA; GSK 1265

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 54713659
  CAS Number: CAS 1051375-10-0
  TTD Drug ID: DMT8J0I
  INTEDE Drug ID: DR1829

Molecule-Related Drug Atlas

Drug(s) Targeting Human immunodeficiency virus Integrase (HIV IN)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dolutegravir	DMCZGRE	Human immunodeficiency virus infection	1C62	Approved	[4]
Raltegravir	DMYURI6	Human immunodeficiency virus infection	1C62	Approved	[5]
Elvitegravir	DMG9B1U	Human immunodeficiency virus infection	1C62	Approved	[4]
Bictegravir, emtricitabine and tenofovir alafenamide	DMG0H8K	Human immunodeficiency virus infection	1C62	Approved	[6]
S-1360	DM9KTSG	Human immunodeficiency virus infection	1C62	Phase 2	[7]
S-364735	DMU7ZMH	Human immunodeficiency virus infection	1C62	Phase 2	[8]
C-2507	DMOFT1V	Human immunodeficiency virus infection	1C62	Phase 1	[9]
Acriflavine	DMKVE8X	Human immunodeficiency virus infection	1C62	Phase 1	[10]
S-265744 LAP	DMDQRWT	Human immunodeficiency virus infection	1C62	Phase 1	[11]
VH4524184	DM1FS0F	Human immunodeficiency virus infection	1C62	Phase 1	[12]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A1 (UGT1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[16]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[19]
Metronidazole	DMTIVEN	Abscess		Approved	[20]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[21]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[22]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A9 (UGT1A9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[23]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[24]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[25]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[26]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[27]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[26]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[26]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[28]
Nateglinide	DMLK2QH	Diabetic complication	5A2Y	Approved	[26]
Haloperidol	DM96SE0	Delirium		Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Integrase (HIV IN)	TT5FH9Y	POL_HV1B1	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[3]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT02951052) Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [3] Disposition and metabolism of cabotegravir: a comparison of biotransformation and excretion between different species and routes of administration in humans. Xenobiotica. 2016;46(2):147-62.
• [4] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [5] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [6] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [7] HIV-1 integrase inhibitors: an emerging clinical reality. Drugs R D. 2007;8(3):155-68.
• [8] The naphthyridinone GSK364735 is a novel, potent human immunodeficiency virus type 1 integrase inhibitor and antiretroviral. Antimicrob Agents Chemother. 2008 Mar;52(3):901-8.
• [9] Elvitegravir: a new HIV integrase inhibitor. Antivir Chem Chemother. 2009 Oct 19;20(2):79-85.
• [10] Why have ten or so nontoxic, retrovirus integrase inhibitors not been made available for AIDS treatment. Biomed Pharmacother. 1999 Dec;53(10):484-6.
• [11] Long-acting shot prevents infection with HIV analogue. Nature. doi:10.1038/nature.2014.14819. 04 March 2014
• [12] Clinical pipeline report, company report or official report of ViiV Healthcare
• [13] Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
• [14] Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
• [15] Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
• [16] UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
• [17] Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
• [18] Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
• [19] Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
• [20] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [21] Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
• [22] Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
• [23] Polymorphic expression of UGT1A9 is associated with variable acetaminophen glucuronidation in neonates: a population pharmacokinetic and pharmacogenetic study. Clin Pharmacokinet. 2018 Oct;57(10):1325-1336.
• [24] Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
• [25] Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4.
• [26] 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.
• [27] The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24.
• [28] The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83.