AZD4547 free base · Synonyms: Fexagratinib | ADSK091

Fexagratinib is a potent inhibitor of the FGFR family.

For research use only. Not for human or veterinary use.

Target FGFR

Research area Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

AZD4547 structure

CAS No.: 1035270-39-3

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
1 g	USD 380.00	BP-01833-1g	In stock	Get quote
2 g	USD 680.00	BP-01833-2g	In stock	Get quote
5 g	USD 1,380.00	BP-01833-5g	In stock	Get quote
10 g	Inquire	BP-01833-10g	Inquire	Inquire

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Description

Fexagratinib (AZD4547; ADSK091) is a potent inhibitor of the FGFR family with IC50s of 0.2 nM, 2.5 nM, 1.8 nM, and 165 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively.

Biological activity

In Vitro Fexagratinib also inhibits recombinant VEGFR2 (KDR) kinase activity with an IC50 of 24 nM. In KG1a, Sum52-PE, MCF7, and KMS11 cell lines, Fexagratinib potently inhibits autophosphorylation of FGFR1, 2, and 3 tyrosine kinases (IC50 values of 12, 2, and 40 nM, respectively) and displays weaker inhibition of FGFR4 cellular kinase activity (IC50=142 nM). Significantly weaker inhibitory activity is observed versus cellular KDR and IGFR ligand-induced phosphorylation (IC50 values of 258 and 828 nM, respectively), representing approximately 20- and 70-fold selectivity over cellular FGFR1. Besides, Fexagratinib potently inhibits FGFR phosphorylation and downstream signaling affected through FRS2, PLCγ, and MAPK at the cellular level. In Vivo Female SCID mice bearing KMS11 tumors are randomized and treated chronically with Fexagratinib at a range of well-tolerated doses. Oral Fexagratinib treatment results in dose-dependent tumor growth inhibition. Twice daily administration of Fexagratinib at 3 mg/kg gives statistically significant tumor growth inhibition of 53% (P<0.0005 by one-tailed t test) when compare with vehicle-treated controls, whereas doses of 12.5 mg/kg once daily and 6.25 mg/kg twice daily results in complete tumor stasis (P<0.0001). A further efficacy study in the KG1a model with 12.5 mg/kg once daily Fexagratinib results in 65% tumor growth inhibition (P=0.002).

Identifiers

SMILES: COC1=CC(OC)=CC(CCC2=CC(NC(=O)C3=CC=C(C=C3)N3C[C@H](C)N[C@H](C)C3)=NN2)=C1
InChIKey: VRQMAABPASPXMW-HDICACEKSA-N

Specifications

MW (average): 463.5719
Formula: C₂₆H₃₃N₅O₃
CAS No.: 1035270-39-3
Physical state: Solid
Color: White to yellow
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

Documents

References

[1]. Gavine PR, et al. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res, 2012, 72(8), 2045-2056.

Same target

Search FGFR

Same research area

Search Cancer