Asciminib

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Chemical Structure| 1492952-76-7 同义名 : ABL001
CAS号 : 1492952-76-7
货号 : A337421
分子式 : C20H18ClF2N5O3
纯度 : 99%+
分子量 : 449.838
MDL号 : MFCD31560488
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(233.42 mM)，配合低频超声助溶，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 Bcr-Abl fusion tyrosine kinase is formed because of a reciprocal chromosomal translocation between chromosomes 9 and 22, producing the Philadelphia chromosome. Bcr-Abl is expressed in chronic myeloid leukemia (CML) and a chronic of acute lymphocytic leukemia[2]. Asciminib is an allosteric inhibitor of the tyrosine kinase activity of Bcr-Abl with IC50 value of 0.5 nM. In vitro, Asciminib inhibited the proliferation of Luc-Ba/F3 cells transformed to express of Bcr-Abl WT and Bcr-Abl T315I with IC50 values of 1.0 nM and 25 nM, respectively[3]. Asciminib was selectively active against Bcr-Abl lines with IC50 values ranging in 1-20 nM, irrespective of the presence of either the p210 or the p190 Bcr-Abl isoformWylie A, Schoepfer J, Jahnke W, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1|Nature, 2017, 543(7647): 733-737|https://www.ncbi.nlm.nih.gov/pubmed/28329763. In vivo, single doses of 7.5, 15 and 30 mg/kg Asciminib, administered to mice bearing KCL-22 xenografts, inhibited pSTAT5 (Tyr694), which returned to baseline at 10, 12 and 16–20h after administration of the dose, respectivelyWylie A, Schoepfer J, Jahnke W, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1|Nature, 2017, 543(7647): 733-737|https://www.ncbi.nlm.nih.gov/pubmed/28329763. Oral administration of 3 mg/kg once daily with Asciminib for 7 days afforded 68-70% tumor growth inhibition, and oral administration of 3 mg/kg twice daily showed tumor regression in KCL-22 mouse xenograft model[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.22mL

0.44mL

0.22mL

11.12mL

2.22mL

1.11mL

22.23mL

4.45mL

2.22mL
参考文献

[1]Wylie AA, Schoepfer J, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature. 2017 Mar 30;543(7647):733-737.

[2]Skorski T. BCR-ABL1 Kinase: Hunting an Elusive Target with New Weapons. Chemistry & Biology, 2011, 18(11): 1352-1353

[3]Schoepfer J, Jahnke W, Berellini G, et al. Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. Journal of Medicinal Chemistry, 2018, 61(18): 8120-8135