DEFACTINIB HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H21F3N8O3S.ClH
Molecular Weight	546.954
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CNC(=O)C1=CC=C(NC2=NC=C(C(NCC3=NC=CN=C3N(C)S(C)(=O)=O)=N2)C(F)(F)F)C=C1

InChI

InChIKey=RCHQNUQAHJNRBY-UHFFFAOYSA-N

InChI=1S/C20H21F3N8O3S.ClH/c1-24-18(32)12-4-6-13(7-5-12)29-19-28-10-14(20(21,22)23)16(30-19)27-11-15-17(26-9-8-25-15)31(2)35(3,33)34;/h4-10H,11H2,1-3H3,(H,24,32)(H2,27,28,29,30);1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

Molecular Formula	C20H21F3N8O3S
Molecular Weight	510.493
Charge	0
Count

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

Description
Sources: https://web.archive.org/web/20170919024026/http://www.verastem.com:80/Verastem-Presentation.pdf
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800029399 | https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=746096

Defactinib is an oral, investigational drug candidate for the treatment of various solid tumors. Through dual inhibition of FAK and PYK2, defactinib targets key resistance mechanisms in the tumor microenvironment (TME), including limited local immune response, dense stroma, and resident cancer stem cells, that may limit the effectiveness of current and investigational treatments. Treatment-related adverse events are: unconjugated hyperbilirubinemia, fatigue and headache.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Focal adhesion kinase 1 15 Target ID: CHEMBL2695 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25971297	Inhibitor 8297		0.6 nM [IC50]
Protein tyrosine kinase 2 beta 3 Target ID: CHEMBL5469 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26334219	Inhibitor 8297		0.6 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Malignant pleural mesothelioma 11 Sources: http://adisinsight.springer.com/trials/700220169 http://www.cancertherapyadvisor.com/lung-cancer/defactinib-receives-orphan-drug-designation-for-mesothelioma/article/304336/	Primary	Phase II 1132	Unknown Approved Use Unknown
Non small cell lung cancer 7 Sources: http://adisinsight.springer.com/drugs/800029399 DOI:10.1358/dof.2014.039.011.2235834	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: http://adisinsight.springer.com/drugs/800029399 http://meetinglibrary.asco.org/content/132341-144	Primary	Phase I 428	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34250	https://www.001chemical.com/chem/search?q=DY34250
001 Chemical	DY34251	https://www.001chemical.com/chem/search?q=DY34251
1PlusChem LLC	1P008TW3	https://www.1pchem.com/search?query=1P008TW3
1PlusChem LLC	1P008U2E	https://www.1pchem.com/search?query=1P008U2E
AChemBlock	M22547	http://www.achemblock.com/catalogsearch/result/?q=M22547
AK Scientific	2361AH	https://aksci.com/item_detail.php?cat=2361AH
AK Scientific	SYN5745	https://aksci.com/item_detail.php?cat=SYN5745
Aceschem	ACF019970	https://www.aceschem.com/catalog/search.do?q=ACF019970
ApexBio Technology	B4800	https://www.apexbt.com/catalogsearch/result/?q=B4800
AstaTech	40965	http://astatechinc.com/CPSResult.php?CRNO=40965
AstaTech	40966	http://astatechinc.com/CPSResult.php?CRNO=40966
Axon MedChem	2574	https://www.axonmedchem.com/product/2574
BLD Pharm	BD629878	http://www.bldpharm.com/search/Search.html?keyword=BD629878
BLD Pharm	BD629879	http://www.bldpharm.com/search/Search.html?keyword=BD629879
Capot Chemical	34080	https://www.capotchem.com/search.do?q=34080
Cayman Chemical	17737	http://www.caymanchem.com/app/template/Product.vm/catalog/17737
Chem Scene	CS-3410	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3410
Chem Scene	CS-3411	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3411
ChemShuttle	140486	https://www.chemshuttle.com/catalogsearch/result/?q=140486
ChemShuttle	169641	https://www.chemshuttle.com/catalogsearch/result/?q=169641
Debye Scientific	DA-34914	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-34914
Debye Scientific	DA-45890	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-45890
Excenen	EX-A1036	http://www.excenen.com/searchresultlist.php?id=EX-A1036
Excenen	EX-A1037	http://www.excenen.com/searchresultlist.php?id=EX-A1037
Excenen	EX-A1049	http://www.excenen.com/searchresultlist.php?id=EX-A1049
Hairui	HR33120	http://www.hairuichem.com/en/product/search.do?q=HR33120
KeyOrganics	AS-17045	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17045
MedChem Express	HY-12289	https://www.medchemexpress.com/search.html?q=HY-12289A&ft=&fa=&fp=
MedChem Express	HY-12289A	https://www.medchemexpress.com/search.html?q=HY-12289A&ft=&fa=&fp=
MolPort	MolPort-035-789-735	https://www.molport.com/shop/molecule-link/MolPort-035-789-735
MolPort	MolPort-046-418-021	https://www.molport.com/shop/molecule-link/MolPort-046-418-021
Molcore	MC34250	http://www.molcore.com/CatMC34250.html
Molcore	MC34251	http://www.molcore.com/CatMC34251.html
Molnova	M10299	https://www.molnova.com/en/serch-list.html?keywords=M10299
Molnova	M10300	https://www.molnova.com/en/serch-list.html?keywords=M10300
MuseChem	I000337	https://www.musechem.com/product/I000337.html
MuseChem	I006418	https://www.musechem.com/product/I006418.html
Selleck Chemicals	S7654	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7654
ShangHai Biochempartner	BCP11299	http://www.biochempartner.com/search_BCP11299
ShangHai Biochempartner	BCP17737	http://www.biochempartner.com/search_BCP17737
TargetMol	T1996	https://www.targetmol.com/search?keyword=T1996
eMolecules	301138918	https://orderbb.emolecules.com/search/#?query=301138918
eMolecules	50283224	https://orderbb.emolecules.com/search/#?query=50283224
eMolecules	50283283	https://orderbb.emolecules.com/search/#?query=50283283
eNovation Chemicals	D501942	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501942&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-5050748387	https://mcule.com/MCULE-5050748387/
mcule	MCULE-6930629501	https://mcule.com/MCULE-6930629501/

PubMed

Title	Date	PubMed
Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src.	1994 Mar	7509446
Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer.	1996 Jan	8770310
Focal adhesion kinase and p53 signaling in cancer cells.	2007	17725966
Liver X receptors as regulators of macrophage inflammatory and metabolic pathways.	2011 Aug	21193033
Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer.	2013 Oct 2	24062525

Patents

Sample Use Guides

In Vivo Use Guide

400 mg twice daily for 12, 21, or 35 days

Route of Administration: Oral

In Vitro Use Guide

Defactinib produces potent in vitro inhibition of A431 epidermoid carcinoma cell-based FAK phosphorylation (IC50=3 nM).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:46:44 GMT 2023` Edited by `admin` on `Sat Dec 16 01:46:44 GMT 2023`
Record UNII	L2S469LM49
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DEFACTINIB HYDROCHLORIDE

Official Name

English

VS-6063 HYDROCHLORIDE

Code

English

BENZAMIDE, N-METHYL-4-((4-(((3-(METHYL(METHYLSULFONYL)AMINO)-2-PYRAZINYL)METHYL)AMINO)-5-(TRIFLUOROMETHYL)-2-PYRIMIDINYL)AMINO)-, HYDROCHLORIDE (1:1)

Systematic Name

English

N-Methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide monohydrochloride

Systematic Name

English

N-METHYL-4-((4-(((3-METHYL(METHYLSULFONYL)AMINOPYRAZIN-2-YL)METHYL)AMINO)-5-(TRIFLUOROMETHYL)PYRIMIDIN-2-YL)AMINO)BENZAMIDE HYDROCHLORIDE

Systematic Name

English

N-METHYL-4-((4-(((3-METHYL(METHYLSULFONYL)AMINO)PYRAZIN-2-YL)METHYL)AMINO)-5-(TRIFLUOROMETHYL)PYRIMIDIN-2-YL)AMINO)BENZAMIDE HYDROCHLORIDE

Systematic Name

English

Defactinib hydrochloride [WHO-DD]

Common Name

English

DEFACTINIB HYDROCHLORIDE [USAN]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/14/1429