Molecular Formula | C21H22ClN3O4 |
Molar Mass | 415.87 |
Storage Condition | -20℃ |
In vitro study | OSI-420 is the major metabolite of Erlotinib in human plasma. After a short intravenous infusion, Erlotinib disappears from the plasma in a biexponential form, with a mean terminal half-life of 5.2 hours and a mean clearance of 128 mL/min/m2. The area under the drug Time curve of OSI-420 in plasma was 30% of that of erlotinib (range 12-59%), and the OSI-420 clearance was more than 5 times higher than that of erlotinib. Erlotinib and OSI-420 are equivalent, and the binding concentration of erlotinib + OSI-420 in CSF can exceed the IC50 (7.9 ng/ml or 20 nM) of EGFR tyrosine kinase inhibition in intact tumor cells. In intact cells, including HNS human head and neck tumor cells (IC50 20nM),DiFi human colon cancer cells, and MDA MB-468 human breast cancer cells, Erlotinib potently inhibits EGFR activation. Erlotinib (1 μm) induces apoptosis in DiFi human colon cancer cells. Erlotinib inhibited the growth of a panel of NSCLC cell lines, including A549,H322,H3255,H358,H661,H1650,H1975,H1299, and H596, with IC50 ranging from 29 nM to> 20 μm. Erlotinib(2 μm) significantly inhibited the growth of AsPC-1 and BxPC-3 pancreatic cancer cells. Combination of Erlotinib HCl with gemcitabine has an additive effect in KRAS-mutant pancreatic cancer cells. 10 μm Erlotinib inhibits EGFR phosphorylation at the Y845 (Src-dependent phosphorylation) and Y1068 (autophosphorylation) sites. OSI-420 in combination with Erlotinib downregulates rapamycin-stimulated Akt activity and produces a coordinated effect on cell growth inhibition. |
In vivo study | At a dose of 100 mg/kg, Erlotinib completely prevented EGFR autophosphorylation in EGF-induced human HN5 tumors grown as xenografts in athymic mice and EGFR autophosphorylation in the liver of treated mice. Erlotinib reduces the growth of xenografted human AML cells. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.405 ml | 12.023 ml | 24.046 ml |
5 mM | 0.481 ml | 2.405 ml | 4.809 ml |
10 mM | 0.24 ml | 1.202 ml | 2.405 ml |
5 mM | 0.048 ml | 0.24 ml | 0.481 ml |
biological activity | OSI-420 (desethylated Erlotinib, CP-473420) is an active metabolite of Erlotinib (an EGFR inhibitor, IC50 is 2 nM). |
Target | Value |
EGFR | 2 nM |