Home Protein Tyrosine Kinase Axl inhibitor - Apoptosis related activator Dubermatinib(TP-0903) For research use only.

Dubermatinib(TP-0903)

TP-0903 is a potent and selective AXL Inhibitor with IC50 of 27 nM. TP-0903 is highly effective in inducing apoptosis.

Dubermatinib(TP-0903) Chemical Structure

Dubermatinib(TP-0903) Chemical Structure

CAS No. 1341200-45-0

Purity & Quality Control

Dubermatinib(TP-0903) Related Products

Biological Activity

Description TP-0903 is a potent and selective AXL Inhibitor with IC50 of 27 nM. TP-0903 is highly effective in inducing apoptosis.
Targets
Axl [1]
(Cell-free assay)
27 nM
In vitro
In vitro

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. [2]
Kinase Assay Axl Kinase activity 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 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 poly-GT substrate. Following addition of ATP and 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 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 Research Cell lines PSN-1 cells
Concentrations --
Incubation Time 96 hours
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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-AKT / AKT / p-SFK / Lyn / Bcl-2 / XIAP / Mcl-1 25673699
In Vivo
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. [3] In mice, SAG (20 μg/g, i.p.) effectively prevents GC-induced neonatal cerebellar developmental abnormalities. [4]
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04518345 Completed
Acute Myeloid Leukemia|Secondary Acute Myeloid Leukemia|Therapy-Related Acute Myeloid Leukemia
Uma Borate|Sumitomo Pharma America Inc.|Ohio State University Comprehensive Cancer Center
 November 5 2020 Early Phase 1
NCT02729298 Completed
Advanced Solid Tumors|EGFR Positive Non-small Cell Lung Cancer|Colorectal Carcinoma|Recurrent Ovarian Carcinoma|BRAF-Mutated Melanoma
Sumitomo Pharma America Inc.
 December 14 2016 Phase 1

Chemical Information & Solubility

Molecular Weight 516.06 Formula

C24H30ClN7O2S
CAS No. 1341200-45-0 SDF Download Dubermatinib(TP-0903) SDF
Smiles CN1CCN(CC1)CC2=CC=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)N(C)C)Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 3 mg/mL ( (5.81 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 2 mg/mL

Water : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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