PF-06439015

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H23FN6O3S
Molecular Weight	470.52
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](OC1=C(N)N=CC(=C1)C2=C(C)N=C(S2)[C@](C)(O)CO)C3=C(C=CC(F)=C3)N4N=CC=N4

InChI

InChIKey=DIXMBHMNEHPFCX-MCMMXHMISA-N

InChI=1S/C22H23FN6O3S/c1-12-19(33-21(28-12)22(3,31)11-30)14-8-18(20(24)25-10-14)32-13(2)16-9-15(23)4-5-17(16)29-26-6-7-27-29/h4-10,13,30-31H,11H2,1-3H3,(H2,24,25)/t13-,22-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C22H23FN6O3S
Molecular Weight	470.52
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24432909

PF-06439015 is a potent and selective inihibitor that overcomes clinical ALK (receptor tyrosine kinase anaplastic lymphoma kinase) mutations resistant to Crizotinib. PF-06439015 is potent across a broad panel of ALK mutant cell lines with an IC50 of 6.6 nM for tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
ALK tyrosine kinase receptor 25 Target ID: CHEMBL4247 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24432909	Inhibitor 8297		0.8 nM [IC50]
Proto-oncogene tyrosine-protein kinase ROS 5 Target ID: CHEMBL5568 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24432909	Inhibitor 8297		0.02 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24432909	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib.	2014 Feb 27	24432909

Sample Use Guides

In Vivo Use Guide

Mouse tumor xenograft study: PF-06439015 showed tumor stasis (100% TGI) at both the 30 mg/kg q.d. and 15 mg/kg b.i.d. doses. The highest dose (50 mg/kg b.i.d) showed significant tumor growth regression (56%) on day 27.

Route of Administration: Oral

In Vitro Use Guide

PF-06439015 inhibited crizotinib-resistant cell line (H3122-L1196M) tumor growth with IC50 6.6 nM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:13:18 UTC 2023` Edited by `admin` on `Sat Dec 16 09:13:18 UTC 2023`
Record UNII	76PND635L1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PF-06439015

Common Name

English

(2R)-2-(5-(6-AMINO-5-((1R)-1-(5-FLUORO-2-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)ETHOXY)-3-PYRIDINYL)-4-METHYL-2-THIAZOLYL)-1,2-PROPANEDIOL

Systematic Name

English

1,2-PROPANEDIOL, 2-(5-(6-AMINO-5-((1R)-1-(5-FLUORO-2-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)ETHOXY)-3-PYRIDINYL)-4-METHYL-2-THIAZOLYL)-, (2R)-

Systematic Name

English

Code System Code Type Description

CAS

1549629-82-4

Created by admin on Sat Dec 16 09:13:18 UTC 2023 , Edited by admin on Sat Dec 16 09:13:18 UTC 2023

PRIMARY

PUBCHEM

72710568

Created by admin on Sat Dec 16 09:13:18 UTC 2023 , Edited by admin on Sat Dec 16 09:13:18 UTC 2023

PRIMARY

FDA UNII

76PND635L1

Created by admin on Sat Dec 16 09:13:18 UTC 2023 , Edited by admin on Sat Dec 16 09:13:18 UTC 2023

PRIMARY

Related Record Type Details


					AA5QJ7X54B

ANAPLASTIC LYMPHOMA KINASE L1196M

TARGET -> INHIBITOR

Qualification:

Ki

Amount:


					6P6Y82PIL1

LEUKOCYTE TYROSINE KINASE RECEPTOR

TARGET -> INHIBITOR


					AA5QJ7X54B

ANAPLASTIC LYMPHOMA KINASE L1196M

TARGET -> INHIBITOR

Comments:

cellular assay

Qualification:

IC50

Amount:

Related Record Type Details


					76PND635L1

PF-06439015

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/24432909

Originator

Approval Year

Targets

Conditions

Approved Use

PubMed

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24432909