OSI-420 is an active metabolite of erlotinib which is an orally active EGFR tyrosin kinase inhibitor with IC50 of 2 and 20 nM for the inhibition of human EGFR and EGFR autophosphorylation in tumor cells. Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m2. OSI-420 exposure (AUC) in plasma was 30% (range 12–59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUCCSF:AUCplasma) of erlotinib and OSI-420 was <5% relative to total plasma concentration, but CSF compound exposure was ∼30% of plasma free compound exposure, which was calculated from published plasma protein binding values. The intravenous administration of erlotinib was well tolerated.
Cell Experiment | |
---|---|
Cell lines | A549, H322, H3255, H358 H661, H1650, H1975, H1299, H596 cells |
Preparation method | Exponentially growing cells are seeded in 96-well plastic plates and exposed to serial dilutions of erlotinib, pemetrexed, or the combination at a constant concentration ratio of 4:1 in triplicates for 72 h. Using cell count and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to assay cell viability . Expressing growth inhibition as the percentage of surviving cells in drug-treated versus PBS-treated control cells (which is considered as 100% viability). The IC50 value is the concentration resulting in 50% cell growth inhibition by a 72-h exposure to drug(s) compared with untreated control cells and is calculated by the CalcuSyn software |
Concentrations | 30 nM-20 μM |
Incubation time | 72 hour |
Animal Experiment | |
---|---|
Animal models | Male 5-week-old BALB-nu/nu mice with HPAC |
Formulation | 6% Captisol |
Dosages | 50 mg/kg |
Administration | Oral administration |
Molecular Weight | 415.87 |
Formula | C21H21N3O4.HCl |
CAS Number | 183320-51-6 |
Solubility (25°C) | DMSO 80 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
Related EGFR/HER2 Products |
---|
BBT-207
BBT-207 is a reversible, mutant-specific EGFR inhibitor with antitumor activity. |
VRN-11
VRN-11 is an EGFR C797S inhibitor. |
TRX-221
TRX-221 is an EGFR C797S inhibitor. |
TAS-3351
TAS-3351 is an EGFR C797S inhibitor. |
Larotinib mesylate hydrate
Larotinib mesylate hydrate is a potent, broad-spectrum, orally active tyrosine kinase inhibitor (TKI) that primarily targets EGFR with an IC50 of 0.6 nM. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.