DACOMITINIB ANHYDROUS

U.S. Department of Health & Human Services Divider Arrow

National Institutes of Health Divider Arrow

NCATS

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H25ClFN5O2
Molecular Weight	469.939
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure of DACOMITINIB ANHYDROUS

Structure Search

SMILES

COC1=C(NC(=O)\C=C\CN2CCCCC2)C=C3C(NC4=CC=C(F)C(Cl)=C4)=NC=NC3=C1

InChI

InChIKey=LVXJQMNHJWSHET-AATRIKPKSA-N

InChI=1S/C24H25ClFN5O2/c1-33-22-14-20-17(24(28-15-27-20)29-16-7-8-19(26)18(25)12-16)13-21(22)30-23(32)6-5-11-31-9-3-2-4-10-31/h5-8,12-15H,2-4,9-11H2,1H3,(H,30,32)(H,27,28,29)/b6-5+

HIDE SMILES / InChI

Molecular Formula	C24H25ClFN5O2
Molecular Weight	469.939
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Approval Year

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:26:48 UTC 2023` Edited by `admin` on `Fri Dec 15 16:26:48 UTC 2023`
Record UNII	2XJX250C20
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DACOMITINIB ANHYDROUS

Common Name

English

(2E)-N-(4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-7-METHOXYQUINAZOLIN-6-YL)-4-PIPERIDIN-1-YLBUT-2-ENAMIDE

Systematic Name

English

PF-00299804

Code

English

dacomitinib [INN]

Common Name

English

Dacomitinib [WHO-DD]

Common Name

English

Code System Code Type Description

INN

9314

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

CAS

1110813-31-4

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

RXCUI

2058848

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

EPA CompTox

DTXSID50149493

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

NCI_THESAURUS

C171723

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

FDA UNII

2XJX250C20

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

PUBCHEM

11511120

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

CHEBI

132268

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

SMS_ID

100000175266

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

DAILYMED

2XJX250C20

Created by admin on Fri Dec 15 16:26:48 UTC 2023 , Edited by admin on Fri Dec 15 16:26:48 UTC 2023

PRIMARY

Related Record Type Details


					76UB6O122H

ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2

TRANSPORTER -> INHIBITOR

Comments:

The reversal effect on ABCB1-overexpressing cells is more potent than that on ABCG2-overexpressing cells. Dacomitinib at 1.0 μM significantly reversed drug resistance mediated by ABCB1 and ABCG2, but not ABCC1, doing so by antagonizing the drug efflux function in ABCB1- and ABCG2-overexpressing cell lines.

Interaction Type:

BINDING

Qualification:

MAY BE CLINICALLY SIGNIFICANT

Amount:


					5092U85G58

SOLVATE->ANHYDROUS


					RO03J093CP

EPIDERMAL GROWTH FACTOR RECEPTOR

TARGET -> INHIBITOR

Interaction Type:

IRREVERSIBLE INHIBITOR


					22ES734693

MULTIDRUG RESISTANCE PROTEIN 1

TRANSPORTER -> INHIBITOR

Comments:

The reversal effect on ABCB1-overexpressing cells is more potent than that on ABCG2-overexpressing cells. Dacomitinib at 1.0 μM significantly reversed drug resistance mediated by ABCB1 and ABCG2, but not ABCC1, doing so by antagonizing the drug efflux function in ABCB1- and ABCG2-overexpressing cell lines.

Interaction Type:

BINDING

Qualification:

MAY BE CLINICALLY SIGNIFICANT

Amount:


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

IN-VITRO


					8E4LAA4357

CYTOCHROME P450 2D6

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

IN-VITRO


					5092U85G58

SALT/SOLVATE -> PARENT

Related Record Type Details


					1Z192N44RY

N-(4-(3-CHLORO-4-FLUORO-ANILINO)-7-METHOXY-QUINAZOLIN-6-YL)-4-(2-OXO-1-PIPERIDYL)BUT-2-ENAMIDE

METABOLITE -> PARENT

Interaction Type:

MINOR

Qualification:

FECAL


					SOA52D3NLL

2-AMINO-3-(3-((4-(3-CHLORO-4-FLUORO-ANILINO)-7-METHOXY-QUINAZOLIN-6-YL)AMINO)-3-OXO-1-(1-PIPERIDYLMETHYL)PROPYL)SULFANYL-PROPANOIC ACID, (2R)-

METABOLITE -> PARENT

Comments:

In addition, it is likely that dacomitinib underwent glutathione conjugation with subsequent hydrolysis to form the cysteine conjugate (M2).

Interaction Type:

MAJOR

Qualification:

FECAL

Amount:


					86YI5K0E85

5-((4-((4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-7-METHOXYQUINAZOLIN-6-YL)AMINO)-4-OXOBUT-2-EN-1-YL)AMINO)PENTANOIC ACID

METABOLITE -> PARENT

Interaction Type:

MINOR

Qualification:

FECAL


					FSU0C3644U

O-DESMETHYL DACOMITINIB

METABOLITE ACTIVE -> PARENT

Comments:

Concentrations of PF-05199265 peaked at 6 h post-dose.

Interaction Type:

MAJOR

Qualification:

PLASMA

Amount:


					FSU0C3644U

O-DESMETHYL DACOMITINIB

METABOLITE ACTIVE -> PARENT

Interaction Type:

MAJOR

Qualification:

FECAL; PLASMA


					FSU0C3644U

O-DESMETHYL DACOMITINIB

METABOLITE ACTIVE -> PARENT

Comments:

Fecal homogenate extracts indicated that metabolism of [14C] dacomitinib was similar and extensive in all the 6 subjects. The four most abundant drugrelated components were dacomitinib (20 %), PF-05199265 (20 %), a cysteine conjugate (M2; 9.5 %), and a monooxygenated metabolite (M7; 5.1 %)

Interaction Type:

MAJOR

Qualification:

FECAL

Amount:

Related Record Type Details


					2XJX250C20

DACOMITINIB ANHYDROUS

ACTIVE MOIETY