product name TP-0903
Description: TP-0903 is a potent and selective AXL Inhibitor with IC50 of 27 nM. TP-0903 induces massive apoptosis in CLL B cells with LD50 values of nanomolar ranges. Combination of TP-0903 with BTK inhibitors augments CLL B-cell apoptosis AXL overexpression is a reoccurring theme observed in multiple tumor types that have acquired resistance to various agents. Treatment of cancer cells with TP-0903 reverses the mesenchymal phenotype in multiple models and sensitizes cancer cells to treatment with other targeted agents. Administration of TP-0903 either as a single agent or in combination with BTK inhibitors may be effective in treating patients with CLL.
References: ACS Med Chem Lett. 2011 Dec 8;2(12):907-912; Clin Cancer Res. 2015 May 1;21(9):2115-26.
516.06
Formula
C24H30ClN7O2S
CAS No.
1341200-45-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 3 mg/mL (5.8 mM)
Water: <1 mg/mL
Ethanol: 1 mg/mL (1.9 mM)
Solubility (In vivo)
0.5% CMC Na+1% Tween 80: 30mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: In pancreatic cancer cells (PSN-1), TP-0903 shows strong antiproliferative activity with IC50 of 6 M. TP-0903 also induces strong G2/M arrest by potently inhibiting Aurora A and B. [1] In CLL B cells from all the patients with CLL, TP-0903 causes a dose-dependent induction of massive apoptosis by targeting phosphorylated Axl, and overcomes CLL BMSC-mediated protection of CLL B cells from apoptosis. Kinase Assay: Test compounds are diluted to desired concentrations in kinase reaction buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT, and 0.01% v/v Tween-20) and are briefly incubated with Axl kinase. The Axl kinase used is recombinant human Axl kinase (catalytic domain, amino acids 473-894) with a histidine tag. The reaction is initiated by the addition of ATP and fluorescein-labeled poly-GT substrate (poly Glu:Tyr, 4:1 polymer). Concentration of the various components in the assay (10 µL reaction volume) are: 1% DMSO, 93 ng/mL Axl kinase, 20 µM ATP, and 200 nM fluorescein poly-GT substrate. Following addition of ATP and fluorescein poly-GT substrate, incubation is for 60 min at room temperature, the enzyme reaction is stopped by addition of 10 µL terbium-labeled anti-phosphotyrosine PY20 antibody in EDTA-containing buffer. Final concentration of EDTA and antibody after addition to the reaction is 10 mM and 2 nM, respectively. The terbium conjugated antibody generates a time-resolved FRET signal with the fluorescein molecule (bound to the poly-GT substrate) when the substrate is phosphorylated. After one hour incubation at room temperature, fluorescence is measured with excitation of 320 nm and dual emission of 495 and 520 nm on an EnVision microplate reader. Signal is expressed in -636996terms of a TR-FRET ratio (fluorescence intensity at 520 nm to 495 nm). Cell Assay: |
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| In Vivo | In the adult rat hippocampus, the intracerebroventricular administration of SAG (2.5 nM) significantly increases the number of newly generated cells and extends survival of hippocampal cells. In mice, SAG (20 μg/g, i.p.) effectively prevents GC-induced neonatal cerebellar developmental abnormalities. |
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| References | ACS Med Chem Lett. 2011 Dec 8;2(12):907-912; Clin Cancer Res. 2015 May 1;21(9):2115-26. |
