INFIGRATINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H31Cl2N7O3
Molecular Weight	560.475
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1CCN(CC1)C2=CC=C(NC3=CC(=NC=N3)N(C)C(=O)NC4=C(Cl)C(OC)=CC(OC)=C4Cl)C=C2

InChI

InChIKey=QADPYRIHXKWUSV-UHFFFAOYSA-N

InChI=1S/C26H31Cl2N7O3/c1-5-34-10-12-35(13-11-34)18-8-6-17(7-9-18)31-21-15-22(30-16-29-21)33(2)26(36)32-25-23(27)19(37-3)14-20(38-4)24(25)28/h6-9,14-16H,5,10-13H2,1-4H3,(H,32,36)(H,29,30,31)

HIDE SMILES / InChI

Description
Sources: https://www.pharmacodia.com/yaodu/html/v1/chemicals/d0b9a6a56ca7fd6ebad617bcda8365a6.html
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/ | DOI: 10.1158/2159-8290.CD-NB2014-057 | http://meetinglibrary.asco.org/content/159420-173

Infigratinib (BGJ398), a potent, orally bioavailable, small-molecule pan-FGFR kinase inhibitor. FGFR genetic alterations are the most significant predictors for BGJ398 sensitivity. It is currently in phase 2 trials for Cholangiocarcinoma, Glioblastoma and Solid tumors. Detected adverse events were hyperphosphatemia, fatigue, constipation, cough and nausea. Other adverse events were generally mild and included stomatitis, hair loss, decreased appetite, and fatigue.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Fibroblast growth factor receptor 1 45 Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21936542	Inhibitor 8228	0.9 nM [IC50]
Fibroblast growth factor receptor 2 25 Target ID: CHEMBL4142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21936542	Inhibitor 8228	1.4 nM [IC50]
Fibroblast growth factor receptor 3 32 Target ID: CHEMBL2742 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21936542	Inhibitor 8228	1.0 nM [IC50]
Fibroblast growth factor receptor 4 16 Target ID: CHEMBL3973 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21936542	Inhibitor 8228	60.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Recurrent glioblastoma 8 Sources: http://adisinsight.springer.com/drugs/800031184	Primary	Phase II 1144	Unknown Approved Use Unknown
Cholangiocarcinoma 17 Sources: http://adisinsight.springer.com/drugs/800031184	Primary	Phase II 1144	Unknown Approved Use Unknown
Solid tumors 144 Sources: https://www.novartis.com/sites/www.novartis.com/files/novartis-pipeline-2015-annual-report.pdf	Primary	Phase II 1144	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P000VYB	https://www.1pchem.com/search?query=1P000VYB
1PlusChem LLC	1P00GULN	https://www.1pchem.com/search?query=1P00GULN
AChemBlock	10291	http://www.achemblock.com/catalogsearch/result/?q=10291
AK Scientific	SYN1152	https://aksci.com/item_detail.php?cat=SYN1152
AK Scientific	Y0313	https://aksci.com/item_detail.php?cat=Y0313
AOBIOUS INC	AOB87703	http://aobious.com/aobious/search?search_query=AOB87703
Ambeed	A107926	http://www.ambeed.com/search/Search.html?keyword=A107926
Angene	AGN-PC-0WH9LV	http://www.angenechemical.com/productshow/AGN-PC-0WH9LV.html
ApexBio Technology	A3014	https://www.apexbt.com/catalogsearch/result/?q=A3014
ApexBio Technology	A3673	https://www.apexbt.com/catalogsearch/result/?q=A3673
AstaTech	FD5035	http://astatechinc.com/CPSResult.php?CRNO=FD5035
Axon MedChem	1775	https://www.axonmedchem.com/product/1775
Axon MedChem	1944	https://www.axonmedchem.com/product/1944
BLD Pharm	BD317674	http://www.bldpharm.com/search/Search.html?keyword=BD317674
BLD Pharm	BD630111	http://www.bldpharm.com/search/Search.html?keyword=BD630111
BOC Sciences	872511-34-7	http://www.bocsci.com/description.asp?cas=872511-34-7
Cayman Chemical	19157	http://www.caymanchem.com/app/template/Product.vm/catalog/19157
Chem Scene	CS-0586	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0586
Chem Scene	CS-1559	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1559
ChemShuttle	109732	https://www.chemshuttle.com/catalogsearch/result/?q=109732
Combi-Blocks	QM-5351	http://www.combi-blocks.com/cgi-bin/find.cgi?QM-5351
Excenen	EX-A057	http://www.excenen.com/searchresultlist.php?id=EX-A057
Excenen	EX-A1550	http://www.excenen.com/searchresultlist.php?id=EX-A1550
KeyOrganics	AS-16290	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16290
Lab Seeker	SC-86751	http://www.labseeker.com/search.php?keywords=SC-86751&category=0
LabSeeker	SC-86751	http://www.labseeker.com/search.php?keywords=SC-86751&category=0
Matrix Scientific	146648	http://www.matrixscientific.com/146648.html
MedChem Express	HY-13311	https://www.medchemexpress.com/search.html?q=HY-13311A&ft=&fa=&fp=
MedChem Express	HY-13311A	https://www.medchemexpress.com/search.html?q=HY-13311A&ft=&fa=&fp=
MolPort	MolPort-023-219-183	https://www.molport.com/shop/molecule-link/MolPort-023-219-183
MolPort	MolPort-042-665-783	https://www.molport.com/shop/molecule-link/MolPort-042-665-783
Molnova	M11248	https://www.molnova.com/en/serch-list.html?keywords=M11248
Molnova	M16344	https://www.molnova.com/en/serch-list.html?keywords=M16344
MuseChem	I007335	https://www.musechem.com/product/I007335.html
ShangHai Biochempartner	BCP000504	http://www.biochempartner.com/search_BCP000504
ShangHai Biochempartner	BCP03602	http://www.biochempartner.com/search_BCP03602
ShangHai Biochempartner	BCP18561	http://www.biochempartner.com/search_BCP18561
TargetMol	T1975	https://www.targetmol.com/search?keyword=T1975
eMolecules	252347413	https://orderbb.emolecules.com/search/#?query=252347413
eMolecules	42777430	https://orderbb.emolecules.com/search/#?query=42777430
eMolecules	50283933	https://orderbb.emolecules.com/search/#?query=50283933
eNovation Chemicals	D572851	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D572851&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D630140	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D630140&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6188401513	https://mcule.com/MCULE-6188401513/
mcule	MCULE-9503046506	https://mcule.com/MCULE-9503046506/

PubMed

Title	Date	PubMed
Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1.	2016 Oct	27558949
Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study.	2017 Jan 10	27870574

Patents

Sample Use Guides

In Vivo Use Guide

1 x 100 mg and 1 x 25 mg capsules once daily for the first 21 days of the 28-day cycle (3 weeks on, 1 week off in a cycle).

Route of Administration: Oral

In Vitro Use Guide

BGJ398 inhibits the proliferation of the FGFR1-, FGFR2-Q, and FGFR3-dependent BaF3 cells with IC50 of 2.9 μM, 2.0 μM and 2 μM, respectively. BGJ398 interferes with autophosphorylation on specific tyrosine residues including FGFR-WT, FGFR2-WT, FGFR3-K650E, FGFR3-S249C and FGFR4-WT with IC50 of 4.6 nM, 4.9 nM, 5 nM, 5 nM and 168 nM, respectively. BGJ398 suppresses proliferation of the cancer cells with wild-type (WT) FGFR3 overexpression such as RT112, RT4, SW780 and JMSU1 with IC50 of 5 nM, 30 nM, 32 nM and 15 nM, respectively.

Name

Type

Language

INFIGRATINIB

Official Name

English

UREA, N'-(2,6-DICHLORO-3,5-DIMETHOXYPHENYL)-N-(6-((4-(4-ETHYL-1-PIPERAZINYL)PHENYL)AMINO)-4-PYRIMIDINYL)-N-METHYL-

Systematic Name

English

BGJ398

Code

English

INFIGRATINIB [USAN]

Common Name

English

3-(2,6-DICHLORO-3,5-DIMETHOXYPHENYL)-1-(6-((4-(4-ETHYLPIPERAZIN-1-YL)PHENYL)AMINO)PYRIMIDIN-4-YL)-1-METHYLUREA

Systematic Name

English

Infigratinib [WHO-DD]

Common Name

English

BGJ-398

Code

English

infigratinib [INN]

Common Name

English

NVP-BGJ398

Code

English

N'-(2,6-DICHLORO-3,5-DIMETHOXYPHENYL)-N-(6-((4-(4-ETHYL-1- PIPERAZINYL)PHENYL)AMINO)-4-PYRIMIDINYL)-N-METHYLUREA

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

707019