ASP5878

Cas No.:	1453208-66-6
Chemical Name:	1H-Pyrazole-1-ethanol, 4-((5-((2,6-difluoro-3,5-dimethoxyphenyl)methoxy)-2-pyrimidinyl)amino)-
Synonyms:	ASP5878;C0Z095LL72;2-(4-((5-((2,6-difluoro-3,5-dimethoxybenzyl)oxy)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)ethanol;2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol;VDZZYOJYLLNBTD-UHFFFAOYSA-N;ASP 5878 [WHO-DD];BCP24820;SB19625;1H-Pyrazole-1-ethanol, 4-((5-((2,6-difluoro-3,5-dimethoxyphenyl)methoxy)-2-pyrimidinyl)amino)-;2-[4-[[5-[(2,6-difluoro-3,5-dimethoxyphenyl)methoxy]pyrimidin-2-yl]amino]pyrazol-1-yl]ethanol;Asp 5878;AS
SMILES:	FC1C(=C([H])C(=C(C=1C([H])([H])OC1=C([H])N=C(N=C1[H])N([H])C1C([H])=NN(C=1[H])C([H])([H])C([H])([H])O[H])F)OC([H])([H])[H])OC([H])([H])[H]
Formula:	C18H19F2N5O4
M.Wt:	407.3714
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	ASP5878 is an oral active and selective inhibitor of the fibroblast growth factor receptor (FGFR), with an IC50 of 3.5 nM for fibroblast growth factor receptor 4 kinase activity. ASP5878 has potential antineoplastic activity[1].
In Vivo:	ASP5878 (3 mg/kg, orally, once daily) shows antitumor activity in a Hep3B2.1-7 subcutaneous xenograft and HCC orthotopic xenograft mouse model[1]. ASP5878 induces shrinkage of FGF19-expressing HCC xenograft model[1]. Animal Model: Four-week-old male nude mice (CAnN.Cg-Foxn1nu/CrlCrlj [nu/nu]) (Hep3B2.1-7 cells inoculated subcutaneously)[1]. Dosage: 3 mg/kg. Administration: Orally once daily from days 14 to 52. Result: Induced tumor regression by 9% and 88% at 1 and 3 mg/kg, respectively, without affecting the body weight for 14 days. Induced the suppression of FGFR4 phosphorylation, mobility shift of FRS2, and suppression of ERK phosphorylation. Animal Model: HCC orthotopic xenograft model (mouse)[1]. Dosage: 3 mg/kg. Administration: Orally once daily for 24 days. Result: Exhibited a lower tumor burden than vehicle- and sorafenibtreated mice. Induced sustained tumor regression without tumor regrowth.
In Vitro:	ASP5878 shows potent antiproliferative activity in most human HCC cell lines[1]. ASP5878 inhibits FGFR4 phosphorylation in a concentration-dependent manner. ASP5878 treatment results in the suppression of phosphorylation, mobility shift of FRS2, and suppression of ERK phosphorylation[1]. Cell Viability Assay[1] Cell Line: Human HCC cell lines. Concentration: 0-10000 nM. Incubation Time: 5 days. Result: HuH-7, Hep3B2.1-7, and JHH-7 cell lines exhibited potent sensitivity to ASP5878, with IC50 values of 27, 8.5, and 21 nmol/L, respectively. The growth inhibition rate of HLF was 64% and those of other ASP5878-sensitive cell lines were higher than 95% at 1000 nM.
References:	[1]. Futami T, et al. ASP5878, a Novel Inhibitor of FGFR1, 2, 3, and 4, Inhibits the Growth of FGF19-Expressing Hepatocellular Carcinoma. Mol Cancer Ther. 2017 Jan;16(1):68-75.