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]
ATC Code
J05AJ04: GSK1265744
J05AJ: Integrase inhibitors
J05A: DIRECT ACTING ANTIVIRALS
J05: ANTIVIRALS FOR SYSTEMIC USE
J: ANTIINFECTIVES FOR SYSTEMIC USE
J05AJ04: GSK1265744
J05AJ: Integrase inhibitors
J05A: DIRECT ACTING ANTIVIRALS
J05: ANTIVIRALS FOR SYSTEMIC USE
J: ANTIINFECTIVES FOR SYSTEMIC USE
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#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
UNII
HMH0132Z1Q
DrugBank ID
DB11751
TTD ID
D08LDB
INTEDE ID
DR1829
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

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]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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.