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A-1210477

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Chemical Structure| 1668553-26-1 同义名 : -
CAS号 : 1668553-26-1
货号 : A116740
分子式 : C46H55N7O7S
纯度 : 99%+
分子量 : 850.037
MDL号 : MFCD28399118
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(10.59 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：

IP 2% DMSO+2% Tween80+30% PEG300+water 0.5 mg/mL clear

PO 0.5% CMC-Na 16 mg/mL suspension

生物活性
靶点

  • Mcl-1

    MCL-1, IC50:26.2 nM
描述 Mcl-1 (induced myeloid leukemia cell differentiation protein), a member of the Bcl-2 family, can regulate apoptosis both in inhibition- or promotion-manner. MCL-1 has also been implicated in mediating resistance to a variety of commonly used chemotherapeutic agents, as well as the Bcl-2 family inhibitor such as ABT-737, ABT-263. A-1210477 is a potent MCL-1 inhibitor with Ki value of 0.454 nM (measure by (TR-FRET)-binding assays), versus Ki values of 132 nM and > 660 nM for BCL-2 and BCL-XL. A-1210477 at concentration of 3 or 30 μM for 4 h caused reduction of MCL-1/Bim association in H929 cells, as well as decreased MCL-1/NOXA interaction in HeLa cells at concentration of 1, 3 and 10 μM for 24 h. For A-1210477 behaved akin to BH3-only proteins, A-1210477 triggered MCL-1 elevation in a variety of cell lines as prediction. A-1210477 each killed H929 cells with IC50 values in the low-μM range, but not the RS4;11 cell line known to rely on BCL-2 for survival, suggesting that the action of A-1210477 is MCL-1-dependent. The synergy on cell killing of A-1210477 ranging in 5-20μM with ABT-263 can be observed in hematological and solid tumor cell lines, BxPC-3, EJ-1, H23, and OPM-2[1].
作用机制 A-1210477 may act as BH3 mimetics that can bind to Mcl-1 and sequester its pro-apoptotic counterpart BIM.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.18mL

0.24mL

0.12mL

5.88mL

1.18mL

0.59mL

11.76mL

2.35mL

1.18mL
参考文献

[1]Leverson JD, Zhang H, et al. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis. 2015.

[2]Lin J, Fu D, et al. Mcl-1 inhibitor suppresses tumor growth of esophageal squamous cell carcinoma in a mouse model. Oncotarget. 2017;8(70):114457-114462.