Details of the Drug

General Information of Drug (ID: DMT8J0I)

• Drug Name: GSK1265744
• 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]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 405.4
  Logarithm of the Partition Coefficient (xlogp); 2.1
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 8
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 145 mgh/L [2]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 8.0 mg/L [2]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 3 h [2]
  Clearance: The clearance of drug in dogs is 0.34 mL/min/kg and in cynomolgus monkeys is 0.32 mL/min/kg [3]
  Elimination: An oral radiolabelled dose of cabotegravir is 58.5% recovered in the feces and 26.8% recovered in the urine [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 41 hours [2]
  Metabolism: The drug is metabolized via UGT1A1 and UGT1A9 [4]
• Chemical Identifiers:
  Formula: C19H17F2N3O5
  IUPAC Name: (3R,6S)-N-[(2,4-difluorophenyl)methyl]-10-hydroxy-6-methyl-8,11-dioxo-4-oxa-1,7-diazatricyclo[7.4.0.03,7]trideca-9,12-diene-12-carboxamide
  Canonical SMILES: C[C@H]1CO[C@H]2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O
  InChI: InChI=1S/C19H17F2N3O5/c1-9-8-29-14-7-23-6-12(16(25)17(26)15(23)19(28)24(9)14)18(27)22-5-10-2-3-11(20)4-13(10)21/h2-4,6,9,14,26H,5,7-8H2,1H3,(H,22,27)/t9-,14+/m0/s1
  InChIKey: WCWSTNLSLKSJPK-LKFCYVNXSA-N
• Cross-matching ID:
  PubChem CID: 54713659
  CAS Number: 1051375-10-0
  DrugBank ID: DB11751
  TTD ID: D08LDB
  INTEDE ID: DR1829

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	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[6]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[6]

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] FDA Approved Drug Products: Vocabria (Cabotegravir) Oral Tablets
• [3] Johns BA, Kawasuji T, Weatherhead JG, Taishi T, Temelkoff DP, Yoshida H, Akiyama T, Taoda Y, Murai H, Kiyama R, Fuji M, Tanimoto N, Jeffrey J, Foster SA, Yoshinaga T, Seki T, Kobayashi M, Sato A, Johnson MN, Garvey EP, Fujiwara T: Carbamoyl pyridone HIV-1 integrase inhibitors 3. A diastereomeric approach to chiral nonracemic tricyclic ring systems and the discovery of dolutegravir (S/GSK1349572) and (S/GSK1265744). J Med Chem. 2013 Jul 25;56(14):5901-16. doi: 10.1021/jm400645w. Epub 2013 Jul 11.
• [4] Davies DS, George CF, Blackwell E, Conolly ME, Dollery CT: Metabolism of terbutaline in man and dog. Br J Clin Pharmacol. 1974 Apr;1(2):129-36. doi: 10.1111/j.1365-2125.1974.tb00221.x.
• [5] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [6] 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.