CH5183284 是一种口服具有活力的，选择性的FGFR抑制剂，能够抑制FGFR1 (IC50:9.3 nM)，FGFR2 (IC50:7.6 nM)，FGFR3 (IC50:22 nM)，FGFR4 (IC50:290 nM)。

CH5183284 is a selective and orally available FGFR inhibitor, which is for FGFR1(IC50=9.3 nM), FGFR2(IC50=7.6 nM), FGFR3(IC50=290), and FGFR4(IC50=22 nM), respectively.

In the DMS114 (FGFR1 amplification), SNU-16 (FGFR2 amplification), and KMS11 cell lines,CH5183284(100 to 300 nM) prevents autophosphorylation of FGFR1, FGFR2, and FGFR3.

Protein kinase assay: The inhibitory activity of CH5183284/Debio 1347 against FGFR1 is evaluated using a radiometric filter assay by measuring the incorporation of 33Pi with a microplate scintillation counter. The phosphorylation activities of LCK, EGFR, KIT, MET, SRC, BRK, FGFR2, Flt3, LTK, INSR, YES, ABL, EPHA2, ZAP70, Fyn, IGF1R, KDR, and PDGFR on substrate peptides are determined by homogeneous time-resolved fluorescence assay with LANCE Eu-W1024 labeled anti-phosphotyrosine PT66 antibody according to standard methods. Time-resolved fluorescence is measured with an EnVision HTS microplate reader. The activities of Aurora A, Akt1/PKBα, PKA, Cdk1/cyclin B, Cdk2/cyclin A, PKCα, PKCβ1 and PKCβ2 on substrate peptides are determined by IMAP FP Screening Express Progressive Binding System. Fluorescence polarization is measured with an EnVision HTS microplate reader.

The cell lines are added to the wells of 96-well plates containing 0.076 to 10,000 nM CH5183284/Debio 1347 and incubated at 37°C. After 4 days of incubation, Cell Counting Kit-8 solution is added and, after incubation for several more hours, absorbance at 450 nm is measured with the iMark Microplate-Reader. The antiproliferative activity is calculated using the formula (1 ? T/C) × 100 (%), where T and C represent absorbance at 450 nm of the cells treated with drugs (T) and that of untreated control cells (C). The IC50 values are calculated using Microsoft Excel 2007.(Only for Reference)

1265229-25-1

C20H16N6O

356.389

CH5183284;Debio 1347;FF284

DMSO:66 mg/mL (185.2 mM)
Ethanol:1 mg/mL (2.8 mM),warmed
Powder: -20°C for 3 years
In solvent: -80°C for 2 years