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: 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.
||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.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
|Body Surface Area (m2)
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by
||Animal B Km
|Animal A Km
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.
||DMSO 3 mg/mL warmed
Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors.
Sinha S, et al. Clin Cancer Res. 2015 May 1;21(9):2115-26. PMID: 25673699.