CABOTEGRAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H17F2N3O5
Molecular Weight	405.3522
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[H][C@@]12CN3C=C(C(=O)NCC4=CC=C(F)C=C4F)C(=O)C(O)=C3C(=O)N1[C@@H](C)CO2

InChI

InChIKey=WCWSTNLSLKSJPK-LKFCYVNXSA-N

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

HIDE SMILES / InChI

Molecular Formula	C19H17F2N3O5
Molecular Weight	405.3522
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Cabotegravir is an investigational drug that is being studied for the treatment and prevention of HIV infection. Cabotegravir belongs to a class (group) of HIV drugs called integrase inhibitors. Integrase inhibitors block an HIV enzyme called integrase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body. Cabotegravir does not require boosting with an additional drug. Two forms of cabotegravir are being studied: tablets that are taken by mouth (known as oral cabotegravir or oral CAB) and a long-acting injectable form that is injected into the muscle (known as cabotegravir LA or CAB LA; LA stands for "long-acting"). (A long-acting drug formulation works over a long period of time. Using this type of drug might mean that the drug could be taken less often, making a treatment or prevention regimen simpler to take.) Cabotegravir is in Phase-III clinical trials for HIV infections.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Human immunodeficiency virus 1 33	Inhibitor 8,297	0.2 nM [IC50]
Solute carrier family 22 member 6 19	Inhibitor 8,297	0.81 µM [IC50]
Solute carrier family 22 member 8 17	Inhibitor 8,297	0.41 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151	Primary		Phase III 656	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3.61 μg/mL	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens
3.39 μg/mL	30 mg single, oral	RIFAMPIN	CABOTEGRAVIR plasma	Homo sapiens
3.4 μg/mL	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens
3.44 μg/mL	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
146 μg × h/mL	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens
59.7 μg × h/mL	30 mg single, oral	RIFAMPIN	CABOTEGRAVIR plasma	Homo sapiens
144 μg × h/mL	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens
146 μg × h/mL	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
38.5 h	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens
16.4 h	30 mg single, oral	RIFAMPIN	CABOTEGRAVIR plasma	Homo sapiens
40.8 h	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens
39.6 h	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.12%	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens
0.17%	30 mg single, oral		CABOTEGRAVIR plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
50 mg single, oral Higher than recommended	healthy, ADULT
800 mg 1 times / 3 months multiple, intramuscular Higher than recommended	healthy, ADULT	Disc. AE: Injection site pain...
30 mg single, oral Recommended	healthy, ADULT
600 mg 1 times / 2 months multiple, intramuscular	unhealthy, ADULT	Disc. AE: Injection site pain...
30 mg 1 times / day multiple, oral Recommended	healthy

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AEs

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AE	Significance	Dose	Population
Injection site pain	4% Disc. AE	800 mg 1 times / 3 months multiple, intramuscular Higher than recommended	healthy, ADULT
Injection site pain	1.7% Disc. AE	600 mg 1 times / 2 months multiple, intramuscular	unhealthy, ADULT

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587 inducer 781	inhibitor 1,767	inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 707 P-gp 1,461 UGT2B7 146 UGT1A3 84 UGT1A6 108 BCRP 699 OATP1B3 706 UGT2B4 19 CYP2B6 810 OCT1 512 CYP2C19 1,478 UGT2B17 18 CYP1A2 1,524 UGT1A4 77 BSEP 402 CYP2C8 911 UGT1A9 116 UGT2B15 64 UGT1A1 204 OATP1B1 788 OCT2 647 MATE1 306 MATE2-K 9 MRP2 383 MRP4 204 OAT3 642 OAT1 599	UGT1A9 380 OATP1B3 350 UGT1A1 418 OCT1 327 P-gp 1,537 BCRP 561 OATP1B1 406	CYP1A2 701 CYP2B6 547

Drug as perpetrator

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Target	Modality	Activity
BCRP 773	inhibitor 3,277	no
BSEP 403	inhibitor 3,277	no
CYP1A2 1,692	inducer 1,573	no
CYP1A2 1,692	inhibitor 3,277	no
CYP2A6 739	inhibitor 3,277	no

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Drug as victim

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Target	Modality	Activity	Clinical evidence
UGT1A1 418	substrate 3,367	major	yes (pharmacogenomic study)
UGT1A9 380	substrate 3,367	minor
OATP1B1 406	substrate 3,367	no
OATP1B3 350	substrate 3,367	no
OCT1 327	substrate 3,367	no

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PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

10, 30, or 60 mg once daily

Route of Administration: Oral

In Vitro Use Guide

Cabotegravir (GSK1265744) inhibited HIV replication with low or subnanomolar efficacy, it inhibited the HIV-1 integrase catalyzed strand transfer reaction with an IC50 of 3.0 nM in vitro. The antiviral EC50 against HIV-1 Ba-L was 0.22 nM, and that against NL432 was 0.34 nM in PBMCs, 0.57 nM using CellTiter-Glo and 1.3 nM using MTT in MT-4 cells, and 0.5 nM in the PHIV assay, which uses a pseudotyped self-inactivating virus.

Substance Class	Chemical
Record UNII	HMH0132Z1Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CABOTEGRAVIR

Official Name

English

GSK1265744A

Code

English

GSK1265744

Code

English

GSK744

Code

English

Apretude

Brand Name

English

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Code System

Code

Type

Description

SMS_ID

100000165751

PRIMARY

INN

9903

PRIMARY

USAN

AB-84

PRIMARY

FDA UNII

HMH0132Z1Q

PRIMARY

CHEBI

172944

PRIMARY

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Related Record

Type

Details


					YY6481J2FF

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INTEGRASE

TARGET -> INHIBITOR

Qualification:

IC50

Amount:

4.94 NANOMOLAR [3.95 to 5.24] (average) [0.02 to 15.64] (limits)


					3L12PT535M

CABOTEGRAVIR SODIUM

SALT/SOLVATE -> PARENT

Amount:


					22ES734693

MULTIDRUG RESISTANCE PROTEIN 1

TRANSPORTER -> SUBSTRATE

Comments:

Cabotegravir is a substrate of P-gp and BCRP in vitro; however, because of its high permeability, no alteration in cabotegravir absorption is expected with coadministration of P-gp or BCRP inhibitors.

Amount:


					0RFO7VC96N

URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A1

METABOLIC ENZYME -> SUBSTRATE

Amount:


					76UB6O122H

ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2

TRANSPORTER -> SUBSTRATE

Comments:

Cabotegravir is a substrate of P-gp and BCRP in vitro; however, because of its high permeability, no alteration in cabotegravir absorption is expected with coadministration of P-gp or BCRP inhibitors.

Amount:

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Related Record

Type

Details


					HMH0132Z1Q

CABOTEGRAVIR

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Referenced Substance	Parameters
Biological Half-life	PHARMACOKINETIC	5.6 weeks [>11.5] (average)	`HMH0132Z1Q` CABOTEGRAVIR
Blood-to-plasma ratio	PHARMACOKINETIC	0.52 (average)	`HMH0132Z1Q` CABOTEGRAVIR	ORAL ADMINISTRATION PHARMACOKINETIC
Tmax	PHARMACOKINETIC	7 hours (average)	`HMH0132Z1Q` CABOTEGRAVIR	ORAL ADMINISTRATION PHARMACOKINETIC

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator