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Purity: ≥98%
Dubermatinib (formerly also known as TP-0903; TP-0903) is a novel, selective and orally bioavailable inhibitor of the AXL receptor tyrosine kinase with potential antineoplastic activity. Its IC50 value for AXL inhibition is 27 nM. Because of its overexpression in various cancer types and its ability to promote tumor growth and metastasis, the receptor tyrosine kinase AXL has gained attention as a possible oncologic target in recent years.
| Targets |
Axl (IC50 = 27nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
In kinase reaction buffer (50 mM HEPES pH 7.5, 10 mM MgCl6, 1 mM EGTA, 2 mM DTT, and 0.01% v/v Tween-20), test compounds are diluted to the desired concentrations and then incubated for a short while with Axl kinase. The catalytic domain of the recombinant human Axl kinase, which has a histidine tag, contains amino acids 473–894. Poly-GT substrate (poly Glu:Tyr, 4:1 polymer) labeled with fluorescein is added to start the reaction. 1% DMSO, 93 ng/mL Axl kinase, 20 µM ATP, and 200 nM fluorescein poly-GT substrate are the concentrations of the different components in the assay (10 µL reaction volume). The enzyme reaction is terminated by adding 10 µL of terbium-labeled anti-phosphotyrosine PY20 antibody in EDTA-containing buffer, after ATP and fluorescein poly-GT substrate have been added and the mixture has been allowed to incubate for 60 minutes at room temperature. EDTA and antibody have final concentrations of 10 mM and 2 nM, respectively, after being added to the reaction. When the substrate is phosphorylated, the terbium-conjugated antibody and fluorescein molecule (bound to the poly-GT substrate) produce a time-resolved FRET signal. 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. The TR-FRET ratio (fluorescence intensity at 520 nm to 495 nm) is used to express the signal in terms of -636996.
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| Cell Assay |
In order to conduct cell proliferation assays, solid white 384-well plates containing 1000 cells per well and 45 µL of the appropriate cell growth media containing 10% FBS are seeded. The plates are then incubated overnight at 37 °C and 5% CO2. The next day, 5 µL is added to each well after the test compounds have been diluted in serum-free growth media to 10 times the desired concentrations. Cells and the combined compound are incubated for ninety-six hours. After the incubation period, each well receives 40 µL of ATP-Lite solution. The wells are then allowed to stand for an extra 10 minutes, and an EnVision microplate reader is used to measure the luminescence. By contrasting the treated wells with the suitable controls (such as the vehicle treated wells) on each plate, the percent cell viability for test compounds is determined.
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| References |
| Molecular Formula |
C24H30CLN7O2S
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| Molecular Weight |
516.06
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| Exact Mass |
515.19
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| Elemental Analysis |
C, 55.86; H, 5.86; Cl, 6.87; N, 19.00; O, 6.20; S, 6.21
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| CAS # |
1341200-45-0
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| Related CAS # |
2305089-34-1 (tartrate);1341200-45-0;
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| Appearance |
Off white to orange solid powder
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| SMILES |
CN1CCN(CC1)CC2=CC=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)N(C)C)Cl
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| InChi Key |
YUAALFPUEOYPNX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H30ClN7O2S/c1-30(2)35(33,34)22-7-5-4-6-21(22)28-23-20(25)16-26-24(29-23)27-19-10-8-18(9-11-19)17-32-14-12-31(3)13-15-32/h4-11,16H,12-15,17H2,1-3H3,(H2,26,27,28,29)
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| Chemical Name |
2-[[5-chloro-2-[4-[(4-methylpiperazin-1-yl)methyl]anilino]pyrimidin-4-yl]amino]-N,N-dimethylbenzenesulfonamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9378 mL | 9.6888 mL | 19.3776 mL | |
| 5 mM | 0.3876 mL | 1.9378 mL | 3.8755 mL | |
| 10 mM | 0.1938 mL | 0.9689 mL | 1.9378 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04518345 | Completed | Drug: Azacitidine Drug: Dubermatinib |
Secondary Acute Myeloid Leukemia Acute Myeloid Leukemia |
Uma Borate | November 5, 2020 | Early Phase 1 |
Impact of TP-0903 treatment on Axl downstream targets, caspase 3 activation and PARP cleavage.Clin Cancer Res.2015 May 1;21(9):2115-26. d |
TP-0903 overcomes CLL BMSC mediated protection of CLL B-cells from apoptosis. Clin Cancer Res. 2015 May 1;21(9):2115-26.Clin Cancer Res.2015 May 1;21(9):2115-26. d |
Combined effect of Axl and BTK inhibition on CLL B-cell survival.Clin Cancer Res.2015 May 1;21(9):2115-26. d |
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