Zipalertinib

Details:

 English name is TAS6417
English synonyms TAS6417; TAS-6417; TAS6417; TAS6417; (S) - N - (4 - amino - 6 - methyl - 5 - (quinolin - 3 - yl) - 8 or 9 - dihydropyrimido [5, 4 - b] indolizin - 8 - yl) acrylamide; 2 - Propenamide, N - [(s) - 4 - amino - 8 or 9 - dihydro - 6 - methyl - 5 - (3 - quinolinyl) pyrChemicalbookimido [5, 4 - b] indolizin - 8 - yl] -; CLN-081; TAS6417TAS-6417; Propenamide, N - [(s) - 4 - amino - 8 or 9 - dihydro - 6 - methyl - 5 - (3 - quinolinyl) pyrimido [5, 4 - b] indolizin - 8 - yl] - (ACI). Zipalertinib(TAS-6417)
CAS number 1661854-97-2
Molecular formula C23H20N6O
Molecular weight 396.44

Boiling point 756.6±60.0°C(Predicted)
Density 1.40±0.1g/cm3(Predicted)
krnitrogen solubility DMSO:20.0(maximum concentration mg/mL); 50.44(Max concentration mM)
Ph coefficient (pKa)12.81±0.40(Predicted)
Color White to yellow

TAS6417 (CLN-081, TPC-064) is a novel EGFR inhibitor that targets EGFR mutants and has low efficacy against wild-type EGFR with IC50 ranging from 1.1 ± 0.1 to 8.0 ± 1.1 nmol/L.

Of the 255 kinases examined, except EGFR, TAS6417 also inhibited 25 other kinases at concentrations below 1000 nm, with IC50 values more than 100 times that of WTEGFR. TAS6417 inhibits TXK,BMX,HER4,TEC,BTK, and JAK3, with an IC50 value less than 10 times its IC5Chemicalbook0 value for WTEGFR. TAS6417 inhibits Ba/F3 cell proliferation driven by multiple EGFR exon 20 mutations, with IC50 ranging from 5.05±1.33nmol/L to 150±53nmol/L. TAS6417 has no effect on EGFR-independent cells such as NCI-H23 and NCI-H460 cells.

In tumor models driven by EGFR exon 20 insertion mutations, TAS6417 induces sustained tumor regression. After administration of TAS6417, the tumor regression effect was rapid and effective throughout the treatment process. Analysis of pharmacokinetic studies showed that after oral administration of 50mg/kg and 100mg/kg of TAS6417 in mice, the plasma concentration of the drug would rapidly decrease within 4 hours of chemicalbook. more... The effective dose of TAS6417 in rats can achieve a lower peak blood concentration than in mice, but the blood concentration in the rat model is more durable and stable, lasting up to 8 hours. In skin tissue, TAS6417 inhibited mutant EGFR but not wild-type EGFR in tumor tissue. TAS6417 prolongs survival in animals with lung cancer.