AZD4547

Cas No.:	1035270-39-3
Chemical Name:	Azd-4547
Synonyms:	AZD4547;AZD-4547;AZD4547 Base;N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3S,5R)-3,5-dimethylpiperazin-1-yl)benzamide;N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide;QCR-89;REL-N-[5-[2-(3,5-DIMETHOXYPHENYL)ETHYL]-1H-PYRAZOL-3-YL]-4-[(3R,5S)-3,5-DIMETHYL-1-PIPERAZINYL]BENZAMIDE;REL-N-[5-[2-(3,5-DIMETHOXYPHENYL)ETHYL]-1H-PYRAZOL-3-YL]-4-[(3R,5S)-3,5-DIMETHYL-1-PIPERAZINYL]BENZ;N-(3-(3,5-dimethoxyphenethyl)-1H-pyrazol-5-yl)-4-((3S,5R)-3,5-dimethylpiperazin-1-yl)benzamide;rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide;N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-rel-3,5-dimethylpiperazin-1-yl)benzamide;AZD 4547;2167OG1EKJ;N-{5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl}-4-(cis-3,5-dimethylpiperazin-1-yl)benzamide;N-{5-[2-(3,5-dimetho
SMILES:	O=C(C1C([H])=C([H])C(=C([H])C=1[H])N1C([H])([H])[C@]([H])(C([H])([H])[H])N([H])[C@]([H])(C([H])([H])[H])C1([H])[H])N([H])C1C([H])=C(C([H])([H])C([H])([H])C2C([H])=C(C([H])=C(C=2[H])OC([H])([H])[H])OC([H])([H])[H])N([H])N=1
Formula:	C26H33N5O3
M.Wt:	463.5719
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	AZD4547 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.
In Vivo:	Female SCID mice bearing KMS11 tumors are randomized and treated chronically with AZD4547 at a range of well-tolerated doses. Oral AZD4547 treatment results in dose-dependent tumor growth inhibition. Twice daily administration of AZD4547 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 AZD4547 results in 65% tumor growth inhibition (P=0.002)[1].
In Vitro:	AZD4547 also inhibits recombinant VEGFR2 (KDR) kinase activity with an IC50 of 24 nM. In KG1a, Sum52-PE, MCF7, and KMS11 cell lines, AZD4547 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, AZD4547 potently inhibits FGFR phosphorylation and downstream signaling affected through FRS2, PLCγ, and MAPK at the cellular level[1].