Dubermatinib (TP-0903) is a potent and selective AXL inhibitor with an IC50 value of 27 nM. TP-0903 induces massive apoptosis in CLL B cells with LD50 values of nanomolar ranges.
In vitro: Dubermatinib (TP-0903) shows extremely potent activity in cell viability assays with an IC50 of 6 nM against the pancreatic cancer cell line PSN-1. TP-0903 is evaluated for its ability to block GAS6-mediated activation of AXL in pancreatic cancer cells. PSN-1 cells are serum-starved and then stimulated with GAS6 in the presence of various concentrations of TP-0903.
CNS Neurosci Ther. 2020 Jul;26(7):777.
Retraction: Receptor tyrosine kinase AXL is correlated with poor prognosis and induces temozolomide resistance in glioblastoma
Dubermatinib purchased from AbMole
CNS Neurosci Ther. 2019 Oct 2.
Receptor tyrosine kinase AXL is correlated with poor prognosis and induces temozolomide resistance in glioblastoma.
Dubermatinib purchased from AbMole
 |
Source | CNS Neurosci Ther (2020 Jul). Figure 5.TP-0903 (Abmole Bioscience, TX, USA) |
| Method | In vitro cell viability assay | |
| Cell Lines | GBM cells | |
| Concentrations | different concentrations | |
| Incubation Time | 3 days | |
| Results | Moreover, an in vitro proliferation assay indicated that TP-0903 attenuated the growth of TMZ-resistant U87 cells, and more importantly, the gained TMZ resistance was significantly reversed by TP-0903. |
| Cell Experiment | |
|---|---|
| Cell lines | PSN-1 cells |
| Preparation method | For cell proliferation assays, 45 µL containing 1000 cells per well are seeded into solid white 384-well plates in appropriate cell growth media containing 10% FBS and incubated overnight at 37 °C and 5% CO2. The following day, test compounds are diluted in serum free growth media to 10x desired concentrations and 5 µL is added to each well. Combined compound and cells are incubated for 96 hours. Following incubation, 40 µL of ATP-Lite solution is added to each well, incubated for an additional 10 minutes at room temperature and luminescence is measured on an EnVision microplate reader. Percent cell viability for test compounds is calculated by comparing treated wells to appropriate controls (e.g. vehicle treated) included on each plate. |
| Concentrations | |
| Incubation time | 96 hours |
| Animal Experiment | |
|---|---|
| Animal models | Female nude mice (6 weeks old) carrying GBM cells |
| Formulation | - |
| Dosages | 20 mg/kg/d |
| Administration | tail vein injection |
| Molecular Weight | 516.06 |
| Formula | C24H30ClN7O2S |
| CAS Number | 1341200-45-0 |
| Solubility (25°C) | DMSO 3 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 TAM Receptor Products |
|---|
| Axl/Mer/CSF1R-IN-2
Axl/Mer/CSF1R-IN-2 is a Axl, Mer and CSF1R inhibitor. |
| AXL-IN-15
AXL-IN-15 is a potent Axl inhibitor with both Ki and IC50 <1 nM. |
| Glesatinib
Glesatinib (MGCD265) is an orally active, potent MET/SMO dual inhibitor. Glesatinib, a tyrosine kinase inhibitor, antagonizes P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in non-small cell lung cancer (NSCLC). |
| DS-1205b free base
DS-1205b free base is a potent and selective inhibitor of AXL kinase, with an IC50 of 1.3 nM. DS-1205b free base also inhibits MER, MET, and TRKA, with IC50s of 63, 104, and 407 nM, respectively. DS-1205b free base can inhibit cell migration in vitro and tumor growth in vivo. |
| Ningetinib Tosylate
Ningetinib Tosylate is a potent, orally bioavailable small molecule tyrosine kinase inhibitor (TKI) with IC50s of 6.7, 1.9 and <1.0 nM for c-Met, VEGFR2 and Axl, respectively. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
