Home Protein Tyrosine Kinase Axl inhibitor Dubermatinib(TP-0903)

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Dubermatinib(TP-0903) Axl inhibitor

Cat.No.S7846

Dubermatinib (TP-0903) is a potent and selective AXL Inhibitor with IC50 of 27 nM, and it is highly effective in inducing apoptosis.
Dubermatinib(TP-0903) Axl inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 516.06

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Quality Control

Batch: Purity: 99.95%
99.95

Solubility

In vitro
Batch:

DMSO : 3 mg/mL (5.81 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 2 mg/mL

Water : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 516.06 Formula

C24H30ClN7O2S

 Storage (From the date of receipt)
CAS No. 1341200-45-0 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CN1CCN(CC1)CC2=CC=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)N(C)C)Cl

Mechanism of Action

Targets/IC50/Ki
Axl
(Cell-free assay)
27 nM
In vitro

In pancreatic cancer cells (PSN-1), Dubermatinib (TP-0903) shows strong antiproliferative activity with IC50 of 6 M. It also induces strong G2/M arrest by potently inhibiting Aurora A and B. [1] In CLL B cells from all the patients with CLL, this compound 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
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 terms of a TR-FRET ratio (fluorescence intensity at 520 nm to 495 nm).
In vivo

In the adult rat hippocampus, the intracerebroventricular administration of Dubermatinib (TP-0903) (2.5 nM) significantly increases the number of newly generated cells and extends survival of hippocampal cells. In mice, this compound (20 μg/g, i.p.) effectively prevents GC-induced neonatal cerebellar developmental abnormalities.

References

Applications

Methods Biomarkers Images PMID
Western blot p-AKT / AKT / p-SFK / Lyn / Bcl-2 / XIAP / Mcl-1
S7846-WB1
25673699

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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