产品说明书

Dubermatinib

Print
Chemical Structure| 1341200-45-0 同义名 : TP-0903
CAS号 : 1341200-45-0
货号 : A173278
分子式 : C24H30ClN7O2S
纯度 : 98%
分子量 : 516.059
MDL号 : MFCD28502172
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 2 mg/mL(3.88 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Axl belongs to the TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases (RTK). The extracellular portion of AXL has properties and structural elements similar to cell adhesion molecules that may participate in cell-to-cell contacts that are not fully understood. In addition to this, AXL binds to the soluble ligand of GAS6 (growth arrest-specific 6) that activates downstream signaling networks responsible for its biological effects. GAS6 binding to AXL results in receptor dimerization and AXL autophosphorylation. This activation results in downstream signaling to the PI3K/AKT, MAPK, and NF-κB pathways. TP-0903 is an Axl kinase inhibitor with IC50 of 27 nM. TP-0903 was active in cell viability assays with an IC50 of 6 nM against the pancreatic cancer cell line PSN-1. PSN-1 cells were stimulated with GAS6 in the presence of the concentrations of 0.03, 0.1, 0.3, 1, 3 or 10 μM of TP-0903. TP-0903 concentration-dependently suppressed phospho-AKT and phospho-AXL levels with EC50s of 305 and 222 nM, respectively[3]. Tumor cells derived from chronic lymphocytic leukemia (CLL) patients were treated by 0.1 μM of TP-0903 and the results were that TP-0903 induced PARP cleavage and caspase-3 activation in 3 of 4 patient samples. In another assay, purified CLL B cells sensitive to TP-0903 were cultured alone or cocultured with CLL BMSCs from 3 different CLL patients followed by treatment with 0.1 mM or 0.175 mM of TP-0903 for 24 h. It was suggested that TP-0903 overcomes CLL BMSC-mediated protection of CLL B cells from apoptosis[4].
作用机制 TP-0903 is an Axl kinase inhibitor. Structural study suggested that TP-0903 interacted with the ATP binding site of Axl kinase. In detail, the pyrimidine nitrogen of TP-0903 was involved in a hydrogen-binding interaction with the Met623 residue in the hinge region of the kinase[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.94mL

0.39mL

0.19mL

9.69mL

1.94mL

0.97mL

19.38mL

3.88mL

1.94mL
参考文献

[1]Sinha S, Boysen J, et al. Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors. Clin Cancer Res. 2015 May 1;21(9):2115-26.

[2]Mollard A, Warner SL, et al. Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors. ACS Med Chem Lett. 2011 Dec 8;2(12):907-912.

[3]Mollard A, Warner SL, Call LT, Wade ML, Bearss JJ, Verma A, Sharma S, Vankayalapati H, Bearss DJ. Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors. ACS Med Chem Lett. 2011 Dec 8;2(12):907-912.

[4]Sinha S, Boysen J, Nelson M, Secreto C, Warner SL, Bearss DJ, Lesnick C, Shanafelt TD, Kay NE, Ghosh AK. Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors. Clin Cancer Res. 2015 May 1;21(9):2115-26.