VU0661013

VU661013 is a novel, potent, selective MCL1 inhibitor with Ki of 97 ± 30 pM of human MCL-1 in a TR-FRET assay. However, VU661013 does not significantly inhibit BCL-xL or BCL-2 with Ki > 40 μM or = 0.73 μM. VU661013 de-stabilizes BIM/MCL-1 association, lea

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5mg

￥5937.00

4750.00

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10mg

￥9175.00

7340.00

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25mg

￥18700.00

14960.00

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50mg

￥29387.00

23510.00

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100mg

￥42212.00

33770.00

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货号: ajce50346
CAS: 2131184-57-9
别名:
分子式: C39H39Cl2N5O4
分子量: 712.66
纯度: >98%
溶解度: DMSO : ≥ 125 mg/mL (175.40 mM);Water : < 0.1 mg/mL (insoluble)
储存: Store at -20°C
库存: 现货

Background

VU661013 is a novel, potent, selective MCL-1 inhibitor that de-stabilizes BIM/MCL-1 association, leads to apoptosis in AML, and is active in venetoclax-resistant cells.[1]

VU661013 is active in patient derived xenografts. In addition, VU661013 is safely combined with venetoclax for synergy in murine models of AML.[1]

[1] Haley E Ramsey, et al. Cancer Discov. 2018 Dec;8(12):1566-1581.

Protocol

Cell experiment:

To generate cells that are resistant to BCL-2 or MCL-1 inhibition, MV-4-11 cells are treated over the course of 3 months with gradually increasing concentrations of VEN (5 nM to 2.5 μM) or VU661013 (100 nM to 5 μM). Cells are declared to be VEN or VU661013-resistant when they are able to maintain 100% viability in the presence of these high concentrations (5 μM of VU661013 and 2.5 μM of VEN) of inhibitors[1].

Animal experiment:

Mice[1]Upon establishing microchimerism, mice are treated with either Venetoclax by daily gavage, VU661013 (10, 25 or 75 mg/kg) by daily i.p injection, or vehicle. VU661013 is dissolved in DMSO and diluted in ethanol, Polyethylene Glycol (PEG), and saline. Venetoclax is dissolved in PEG and ethanol, and diluted with Phosal 50 PG. Peripheral blood is assessed weekly for human chimerism. Spleen/body ratio is calculated as organ weight (gram) per gram of body weight[1].

参考文献:

[1]. Haley E. Ramsey, et al. A Novel MCL-1 Inhibitor Combined with Venetoclax Rescues Venetoclax Resistant Acute Myelogenous Leukemia. Cancer Discov. August 28, 2018.