Fexagratinib

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H33N5O3
Molecular Weight	463.5719
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(OC)=CC(CCC2=CC(NC(=O)C3=CC=C(C=C3)N4C[C@H](C)N[C@H](C)C4)=NN2)=C1

InChI

InChIKey=VRQMAABPASPXMW-HDICACEKSA-N

InChI=1S/C26H33N5O3/c1-17-15-31(16-18(2)27-17)22-9-6-20(7-10-22)26(32)28-25-13-21(29-30-25)8-5-19-11-23(33-3)14-24(12-19)34-4/h6-7,9-14,17-18,27H,5,8,15-16H2,1-4H3,(H2,28,29,30,32)/t17-,18+

HIDE SMILES / InChI

Molecular Formula	C26H33N5O3
Molecular Weight	463.5719
Charge	0
Count

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

Description
Sources: https://openinnovation.astrazeneca.com/azd4547.html
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22369928 http://adisinsight.springer.com/drugs/800030912

AZD-4547 is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. FGFR inhibitor AZD4547 binds to and inhibits FGFR, which may result in the inhibition of FGFR-related signal transduction pathways, and, so, the inhibition of tumor cell proliferation and tumor cell death. FGFR, up-regulated in many tumor cell types, is a receptor tyrosine kinase essential to tumor cellular proliferation, differentiation and survival. AZD-4547 is a selective FGFR inhibitor targeting FGFR1/2/3 with IC50 of 0.2 nM/2.5 nM/1.8 nM in cell-free assays, weaker activity against FGFR4, VEGFR2 (KDR), and little activity observed against IGFR, CDK2, and p38. Compared to FGFR1-3, AZD-4547 displays weaker activity against FGFR4 with IC50 of 165 nM. AZD-4547 only inhibits recombinant VEGFR2 (KDR) kinase activity with IC50 of 24 nM, in the in vitro selectivity test against a diverse panel of representative human kinases. AZD-4547 is under clinical investigation for the treatment of FGFR-dependent tumors. It is in phase II clinical studies for the treatment of breast cancer; gastric cancer; lung cancer; oesophageal cancer and in phase II/III clinical studies for the treatment of non-small cell lung cancer.

CNS Activity

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/22369928	Inhibitor 8297	0.2 nM [IC50]
Fibroblast growth factor receptor 2 25 Target ID: CHEMBL4142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22369928	Inhibitor 8297	2.5 nM [IC50]
Fibroblast growth factor receptor 3 32 Target ID: CHEMBL2742 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22369928	Inhibitor 8297	1.8 nM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22369928	Inhibitor 8297	24.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastric cancer 53 Sources: https://clinicaltrials.gov/ct2/show/NCT01457846	Primary		Phase II 1132	Unknown Approved Use Unknown
Squamous cell lung carcinoma 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02965378	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
215.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28070720	120 mg 2 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AZD-4547 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
216.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28070720	160 mg 2 times / day single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	AZD-4547 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
302.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28070720	160 mg 1 times / day steady-state, oral dose: 160 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AZD-4547 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
2072 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28070720	120 mg 2 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AZD-4547 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3417 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28070720	160 mg 2 times / day single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	AZD-4547 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4134 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28070720	160 mg 1 times / day steady-state, oral dose: 160 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AZD-4547 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
27.96 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28070720	160 mg 2 times / day single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:		AZD-4547 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116243	https://www.001chemical.com/chem/search?q=DY116243
1PlusChem LLC	1P008TUF	https://www.1pchem.com/search?query=1P008TUF
AChemBlock	M15639	http://www.achemblock.com/catalogsearch/result/?q=M15639
AK Scientific	2240AH	https://aksci.com/item_detail.php?cat=2240AH
AK Scientific	SYN5755	https://aksci.com/item_detail.php?cat=SYN5755
AOBIOUS INC	AOB87745	http://aobious.com/aobious/search?search_query=AOB87745
ApexBio Technology	A8350	https://www.apexbt.com/catalogsearch/result/?q=A8350
Apollo Scientific	BIM1188	http://www.apolloscientific.co.uk/chemical_results.php?qstext=BIM1188&product_group=%25&search_fieldname=header_search
AstaTech	41335	http://astatechinc.com/CPSResult.php?CRNO=41335
AstaTech	41570	http://astatechinc.com/CPSResult.php?CRNO=41570
Axon MedChem	1917	https://www.axonmedchem.com/product/1917
Cayman Chemical	13111	http://www.caymanchem.com/app/template/Product.vm/catalog/13111
Chem Scene	CS-0971	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0971
ChemShuttle	100943	https://www.chemshuttle.com/catalogsearch/result/?q=100943
Combi-Blocks	QV-4739	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-4739
Excenen	EX-A1578	http://www.excenen.com/searchresultlist.php?id=EX-A1578
KeyOrganics	AS-17054	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17054
Matrix Scientific	143733	http://www.matrixscientific.com/143733.html
MedChem Express	HY-13330	https://www.medchemexpress.com/search.html?q=HY-13330&ft=&fa=&fp=
MolPort	MolPort-023-293-558	https://www.molport.com/shop/molecule-link/MolPort-023-293-558
Molcore	MC116243	http://www.molcore.com/CatMC116243.html
Molnova	M10175	https://www.molnova.com/en/serch-list.html?keywords=M10175
MuseChem	I000212	https://www.musechem.com/product/I000212.html
Ryan Scientific	Tenovin-1	https://ryansci.com/products?q=Tenovin-1&list_q=&search_type=exact
ShangHai Biochempartner	BCP000418	http://www.biochempartner.com/search_BCP000418
Synthonix	14760	https://synthonix.com/catalogsearch/result/?q=14760
Toronto Research Chemicals	A808120	https://www.trc-canada.com/product-detail/?CatNum=A808120
Toronto Research Chemicals	B693765	https://www.trc-canada.com/product-detail/?CatNum=B693765
eMolecules	300790293	https://orderbb.emolecules.com/search/#?query=300790293
eMolecules	44818034	https://orderbb.emolecules.com/search/#?query=44818034
eMolecules	48875851	https://orderbb.emolecules.com/search/#?query=48875851
eMolecules	55540443	https://orderbb.emolecules.com/search/#?query=55540443
eMolecules	93430633	https://orderbb.emolecules.com/search/#?query=93430633
eNovation Chemicals	D573213	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D573213&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6351519169	https://mcule.com/MCULE-6351519169/

PubMed

Title	Date	PubMed
		252160568
Design, synthesis and biological evaluation of novel FGFR inhibitors bearing an indazole scaffold.	2015 Jul 28	26080733

Patents

Sample Use Guides

In Vivo Use Guide

AZD-4547 taken orally in tablet formation, 80mg b.d., in a 2 week on, 1 week off schedule

Route of Administration: Oral

In Vitro Use Guide

AZD-4547 has potent in vitro antiproliferative activity only against tumor cell lines expressing deregulated FGFRs such as KG1a, Sum52-PE, and KMS11 with IC50 of 18-281 nM

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:46:51 UTC 2023` Edited by `admin` on `Sat Dec 16 01:46:51 UTC 2023`
Record UNII	2167OG1EKJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Fexagratinib

Official Name

English

fexagratinib [INN]

Common Name

English

ABSK-091

Code

English

AZD4547

Code

English

ABSK091

Code

English

KB-74810

Code

English

AZD-4547

Code

English

N-(5-(2-(3,5-DIMETHOXYPHENYL)ETHYL)-1H-PYRAZOL-3-YL)-4-((3R,5S)-3,5-DIMETHYLPIPERAZIN-1-YL)BENZAMIDE

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

863921