CPL304110 is a potent, orally active and selective inhibitor of fibroblast growth factor receptors FGFR (1-3), with IC50 values of 0.75 nM, 0.5 nM, and 3.05 nM for FGFR (1-3), respectively.
IC50&Target
FGFR1
0.75 nM (IC50)
FGFR2
0.5 nM (IC50)
FGFR3
3.05 nM (IC50)
体外研究
CPL304110 (0-0.6 μM) dose-dependently inhibits FGFR2 phosphorylation and downstream signaling (p-ERK).
CPL304110 (compound 56q) exhibits in SNU-16 proliferation assay with an IC50 of 85.64 nM.
CPL304110 (compound 56q) demonstrats a more than 45-fold, 345-fold, 395-fold and 680-fold selectivity over KDR (VEGFR2), Flt3, Aura A and PDGFRb, respectively relative to FGFR2, and no significant inhibitory effects were observed with other tyrosine kinases.
Western Blot Analysis
Cell Line:
SNU-16 cell lines.
Concentration:
0-0.6 μM.
Incubation Time:
1 h.
Result:
Suppressed FGFR2 phosphorylation and downstream signaling (p-ERK)
体内研究
CPL304110 (p.o., 40 mg/kg) exhibits a t1/2 of 2 h and Cmax of 3369 ng/mL in mice.
CPL304110 (compound 56q, 2 X 20 mg/kg) significantly inhibits tumor growth in mice without significant body loss or any toxicity. On day 21 (D21, day of termination) the tumor growth inhibition (TGI) is 64% for dosing 20 mg/kg twice a day.
Animal Model:
Severe combined immunodeficient (SCID) mice implanted subcutaneously with SNU-16 (human).
Dosage:
20 mg/kg (X2).
Administration:
Orally, twice daily for 21 days.
Result:
After 6 hours of last dosing, concentration of 56q decreased in the plasma (9%) but increased stepwise in the tumor cells (121%).
分子式
C25H30N6O2
分子量
446.54
CAS号
1627826-19-0
运输条件
Room temperature in continental US; may vary elsewhere.