Drug Information

Drug (ID: DG00116) and It's Reported Resistant Information

• Name: Cabotegravir
• 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:
  In total 1 Indication(s)
  Human immunodeficiency virus disease [ICD-11: 1C60-1C62]; Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  HIV infection [ICD-11: 1C62]; [1]
• Target: Human immunodeficiency virus Integrase (HIV IN); POL_HV1B1; [1]
• Formula: C19H17F2N3O5
• IsoSMILES: 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: 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
• PubChem CID: 54713659
• TTD Drug ID: D08LDB
• INTEDE ID: DR1829
• DrugBank ID: DB11751

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

HIV infection [ICD-11: 1C62]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.E10D+p.S17T+p.S39N+p.I72V+p.S119P+p.T122I+p.T124N+p.T125A+p.V151I+p.N155H+p.N222K+p.P261A
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q176H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.D6T+p.K7E+p.S17N+p.V54I+p.I72V+p.L74M+p.V79I+p.T97A+p.L101I+p.I113L+p.S119R+p.T122I+p.T124N+p.T125A+p.E138K+p.G140A+p.I141AT+p.S147SG+p.Q148R+p.K156N+p.I203M+p.I208M+p.L234V+p.D253E
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q184H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.K14R+p.V31I+p.V32I+p.L45Q+p.L101I+p.T112V+p.T125A+p.G134N+p.I135V+p.K136T+p.Y143C+p.V201I+p.T206S+p.S230R+p.L234I+p.N254NS+p.R269K+p.D270H
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q174H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.E11D+p.K14R+p.S17T+p.V31I+p.L45V+p.A91S+p.L101I+p.T124A+p.E138Q+p.G140C+p.Q148R+p.V151I+p.K219N+p.N222K+p.L234I+p.V259I
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q182H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.E11D+p.V31I+p.G70R+p.I84V+p.L101I+p.S119P+p.T122I+p.N155H+p.G163E+p.V201I+p.D256E
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q175H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.K14R+p.S24G+p.D25E+p.S39C+p.I60IM+p.L63I+p.T97A+p.L101I+p.S119SR+p.T124N+p.T125A+p.I135V+p.E138T+p.G140S+p.Q148H+p.M154I+p.V165I+p.V201I+p.V259VI
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q183H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.G59D+p.I60V+p.E138K+p.Q148R+p.K173R+p.T218S+p.S230N+p.M275S+p.C280S
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q180H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.E11D+p.S17C+p.L68V+p.L101I+p.T124N+p.T125A+p.I135V+p.G140A+p.Q148R+p.D253E+p.V281M
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q181H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.K14R+p.V31I+p.T97A+p.L101I+p.T112V+p.S119R+p.T124A+p.T125S+p.G134N+p.K136T+p.N155H+p.V165I+p.V201I+p.T206S+p.Y227F+p.L234I+p.S255N+p.D256E+p.S283G
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q178H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.S17N+p.R20K+p.M50I+p.V77A+p.L101I+p.T112I+p.T124A+p.T125A+p.K136Q+p.G193E+p.V201I+p.T206S+p.T218L+p.I220V+p.L234V+p.D256E+p.R263K+p.D279G+p.S283G
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q179H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.K14R+p.E69ED+p.E138K+p.G140S+p.Q148H+p.M154I+p.N155H+p.V201I
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q185H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.S17N+p.D25E+p.S119G+p.T122I+p.T124N+p.T125A+p.M154I+p.N155H+p.K156R+p.T206S+p.T218S
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q177H/k/R plus one to two additional INSTI mutations.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.S17N+p.S39R+p.L45V+p.M50ML+p.T66A+p.V75I+p.L101I+p.T124A+p.K127R+p.S147SG+p.G163K+p.V201I
• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q168H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.A23T+p.S24G+p.D25E+p.L28I+p.I72V+p.T124A+p.Q148R+p.V165I+p.L172LF+p.H183HP+p.Q209QP+p.A239AT
• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q169H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.K7KR+p.S17N+p.I72V+p.I84L+p.T97A+p.L101I+p.T112I+p.S119P+p.T122I+p.T124N+p.T125A+p.K136Q+p.Y143R+p.V201I+p.A205S+p.K211R+p.T218L+p.L234V+p.D256E+p.I268L+p.D270H
• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q170H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.S17N+p.M154L+p.N155H+p.V201I+p.D232N+p.L242LF
• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q171H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.K14R+p.S24H+p.V31I+p.L68I+p.I73V+p.E92Q+p.L101I+p.T112V+p.S119T+p.T124G+p.T125A+p.G134N+p.K136T+p.V165I+p.V201I+p.T206S+p.L234I+p.D256E+p.S283G
• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q167H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.E11D+p.R20K+p.E92Q+p.V201I+p.K211R+p.S230SN+p.D232E+p.D256E
• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q172H/k/R plus one to two additional INSTI mutations.

Key Molecule: HIV1 Integrase (HIV1 IT) [1]

• Molecule Alteration: Missense mutation; p.K14R+p.L101V+p.T112I+p.T125V+p.N155H+p.E157Q+p.K160Q+p.G193E+p.S230N+p.L234I+p.A265V+p.D279G
• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TZM-bl cells; Uterus; Homo sapiens (Human); CVCL_B478
• Experiment for Molecule Alteration: Population sequencing of the integrase region assay
• Experiment for Drug Resistance: TZM-bl cell line-based phenotypic assay
• Mechanism Description: In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q173H/k/R plus one to two additional INSTI mutations.

References

• Ref 1: Comparable In Vitro Activities of Second-Generation HIV-1 Integrase Strand Transfer Inhibitors (INSTIs) on HIV-1 Clinical Isolates with INSTI Resistance Mutations. Antimicrob Agents Chemother. 2019 Dec 20;64(1):e01717-19. doi: 10.1128/AAC.01717-19. Print 2019 Dec 20.