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A-1210477

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验、�/div>

CAS NO:	1668553-26-1
规格:	�?8%

包装与价格：

包装	价格(�?
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议

产品介绍

理化性质和储存条仵�/div>

Molecular Weight (MW)	850.04
Formula	C46H55N7O7S
CAS No.	1668553-26-1
Storage	-20� for 3 years in powder form
Storage	-80� for 2 years in solvent
Solubility(In vitro)	DMSO: 3 mg/mL (3.5 mM)
	Water: <1 mg/mL (slightly soluble or insoluble)
	Ethanol: <1 mg/mL
Synonyms	A-1210477; A 1210477; A1210477

实验参考方泔�/div>

In Vitro	A-1210477 (10 μM) reduces the amount of BIM co-immunoprecipitated with MCL-1 antibody, and triggers MCL-1 elevation in a variety of cancer cell lines, including the breast cancer cell line HCC-1806. A-1210477 inhibits MCL-1-NOXA interactions with an IC50 of approximately 1 μM, while having no effect on BCL-2-BIM or BCL-XL-BCL-XS interactions. The NSCLC cell lines H2110 and H23 are sensitive to A-1210477 with cell viability IC50<10 μM, confirming that A-1210477 can kill MCL-1-dependent cell lines. A-1210477 induces extensive concentration-dependent apoptosis in H929 cells following a brief (4 h) exposure. A-1210477 interacts with MCL-1 with Kd of appr 740 nM. A-1210477 (10 μM) induces extensive mitochondrial fragmentation in a DRP-1-dependent manner[2]. A-1210477 upregulates MCL-1 expression in BRAF-mutant CRC cells and in the melanoma cell line A375 in a dose-dependent manner. A-1210477 releases BAK from MCL-1 and cobimetinib induces BIM that is required for BAX activation. A-1210477 (0, 5, 10 and 15 μM) has minimal effect on cell viability but substantially sensitizes resistant BCL2High NHL cell lines to navitoclax.
Kinase Assay	TR-FRET-binding affinity assays are performed for BCL-2, BCL-XL, and MCL-1 in 4.52 mM monobasic potassium phosphate, 15.48 mM dibasic potassium phosphate, 1 mM sodium EDTA, 0.05% Pluronic F-68 detergent, 50 mM sodium chloride, and 1 mM DTT (pH 7.5) for BCL-XL.6 For MCL-1 assays, GST-tagged MCL-1 (1 nM) is mixed with 100 nM f-Bak, 1 nM Tb-labeled anti-GST antibody, and compound at room temperature (RT) for 60 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-GST antibody) emission filters.
Cell Assay	Adherent cell lines are seeded at 50 000 cells per well in 96-well plates and treated for 48 h with compounds diluted in half-log steps starting at 30 μM and ending at 0.001 μM. Multiple myeloma cell lines are seeded at 15 000-20 000 cells per well and treated similarly. Effects on proliferation and viability are determined using CellTiter-Glo reagent from Promega according to the manufacturer's instructions. IC50 values are determined by non-linear regression analysis of the concentration response data.
Dosages	N/A
Administration	N/A
Reference	Blood Cancer J. 2015 Nov 13;5:e368

生物活�?/div>

Loss of MCL-1 function modulates BAK expression. SKBR3 cells were treated with MCL-1 siRNA (#5), scrambled siRNA (Sc; both 20 nmol/L) or the MCL-1 inhibitor A-1210477 for 8 hours and the effect on MCL-1, PARP, and BAK determined by Western blot analysis (A) or by RT-PCR (B). Mol Cancer Ther October 1 2016 15 (10) 2273-2281

BCL-XL limits the efficacy of A-1210477 to a greater extent than BCL-2. SKBR3 cells overexpressing BCL-XL or BCL-2 were treated with A-1210477 for 24 hours and the percentage of apoptosis determined from the sub-G0–G1 DNA content of DNA cell-cycle histograms and compared with vector control (Vct Ctrl) or parental cell lines (wild-type, WT).

BIM redistribution mediated by loss in function of antiapoptotic BCL-2 proteins.