VU661013

Catalog No.S8758 Batch:S875801

Technical Data

Formula

C₃₉H₃₉Cl₂N₅O₄

Molecular Weight

712.66

CAS No.

2131184-57-9

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (140.31 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	5.0mg/ml
	5% DMSO 1 95% Corn oil	0.6mg/ml

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

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, leads to apoptosis in AML.

Targets

MCL1 ^[1]
(Cell-free assay)

97 pM(Ki)

In vitro

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]

In vivo

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

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MV4-11 cells Concentrations 100 nM - 5 μM Incubation Time 48 h Method To generate cells that are resistant to BCL-2 or MCL-1 inhibition, MV4-11 cells are treated over the course of 3 months with gradually increasing concentrations of VEN (5nM to 2.5 μM) or VU661013 (100nM 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.
Animal Study:^{^[1]}	Animal Models 6–8 weeks old female NSGS [NOD-scid IL2Rgnull3Tg(hSCF/hGM-CSF/hIL3)] mice Dosages 10 mg/kg, 25 mg/kg, 75 mg/kg Administration IP

Cell Assay:^{^[1]}

Cell lines
MV4-11 cells
Concentrations
100 nM - 5 μM
Incubation Time
48 h
Method
To generate cells that are resistant to BCL-2 or MCL-1 inhibition, MV4-11 cells are treated over the course of 3 months with gradually increasing concentrations of VEN (5nM to 2.5 μM) or VU661013 (100nM 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.

Animal Study:^{^[1]}

Animal Models
6–8 weeks old female NSGS [NOD-scid IL2Rgnull3Tg(hSCF/hGM-CSF/hIL3)] mice
Dosages
10 mg/kg, 25 mg/kg, 75 mg/kg
Administration
IP

References

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.