embalaje : 5mg
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VU661013 is a novel, potent, selective MCL-1 inhibitor (Ki of 97 ± 30 pM).[1]
MCL-1, an anti-apoptotic BCL-2 family member, is commonly upregulated in acute myeloblastic leukemia (AML) cells. Targeting anti-apoptotic proteins in AML is a key therapeutic strategy, and MCL-1 is a critical anti-apoptotic oncoprotein. [1]
VU661013 reduced expansion of multiple AML cell lines in vitro. Venetoclax (a BCL-2 inhibitor) and VU661013 exhibited favorable synergy in several of AML cells lines, venetoclax-resistant AML cells were sensitive to VU661013. [1]
VU661013 decreased tumor growth in an in vivo murine model. VU661013 (25mg/kg) and venetoclax (15mg/kg) can be synergistic in patient-derived xenograft transplantation models. [1]
Reference:
[1]A Novel MCL-1 Inhibitor Combined with Venetoclax Rescues Venetoclax Resistant Acute Myelogenous Leukemia. Cancer Discov. 2018 Sep 5. PMID: 30185627. DOI: 10.1158/2159-8290.CD-18-0140
Cell lines
AML cell lines MV-411, Kasumi-1, K-562, HL-60, U-937 Kasumi-3, KG-1, NB4, SKM-1, PL-21, MOLM-16 and THP-1, and leukemia mantle cell lymphoma cell line Z-138.
Preparation method
This compound can be soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.
Reaction Conditions
48 h, 100 nM to 5 μM
Applications
Multiple AML cell lines displayed a high sensitivity to VU661013.
Animal models
Xenograft transplantation model of MV-4-11 cell line in NSGS mice; AML patient PDX models
Dosage form
10, 25 or 75 mg/kg , daily i.p injection for 21 days
VU661013 treatment of disseminated human AML resulted in a dose-dependent decrease in tumor burden.
Other notes
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: