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The company added that BLU-554 (CS3008) is an oral, potent highly selective and irreversible inhibitor of FGFR4, with a precise selectivity for FGFR4 that spares the paralog kinases FGFR1, FGFR2 and FGFR3.
Compound deletion of Fgfr3 and Fgfr4 partially rescues the Hyp mouse phenotype.
Previous studies have demonstrated that the transcript variants of Fgfr1 Iiib and IIIc, Fgfr2 IIIc, Fgfr3 IIIc and Fgfr4 are expressed in fetal, immature and adult rat testes (10).
FGFR4 protein was expressed at similar levels in RO82W-1 and normal thyroid cells.
AKT1 CTNNB1 FGFR1 GNAS KRAS NRAS PIK3R5 STAT1 AKT2 EGFR FGFR2 HRAS MAP2K1 NTRK1 PKHD1 TEC AKT3 ERBB2 FGFR3 IDH1 MAP2K2 NTRK2 PRKCB1 TP53 (HER2) ALK ERCC6 FGFR4 IDH2 MAP2K7 NTRK3 RAF1 BRAF FBX4 FOXL2 IGF1R MET PDGFRA RET CDK4 FBXW7 GNA11 KDR MYC PIK3R1 SMO CSF1R FES GNAQ KIT NEK9 PIK3R4 SOS1
There is some evidence of downstream signaling differences between different FGFRs, such as the difference in activation levels of the MAPK pathway between FGFR1 and FGFR4 as determined using Xenopus animal cap assays (Umbhauer et al., 2000).
In this study, 15 single-nucleotide polymorphisms (SNPs) from seven genes (SHP, ASBT, Klotho-beta, FGFR4, OST-alpha, OST-beta, and CYP7A1) were analyzed.
The gene produces a substance called fibroblast growth factor receptor 4 (FGFR4).
The team will combine both biology and chemistry expertise to develop small molecule inhibitors against protein tyrosine kinases FGFR4 and Ack1.
RESULTS: Chlorpyrifos and diazinon both markedly suppressed fgf20 expression in the forebrain and fgf2 in the brain stem, while elevating brain stem fgfr4 and evoking a small deficit in brain stem fgf22.
M2 EQUITYBITES-January 29, 2019-CStone wins CTA's approval in China to begin Phase I trial for FGFR4 inhibitor BLU-554 (CS3008)
M2 PHARMA-January 29, 2019-CStone wins CTA's approval in China to begin Phase I trial for FGFR4 inhibitor BLU-554 (CS3008)
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- FGFR signalling adaptor
- FGFR substrate 2
- FGFR-signalling adaptor SNT