A8783-5mg | VU661013 [2131184-57-9] Clinisciences

Background

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

Chemical Properties

Storage	Store at -20°C
M.Wt	712.66
Cas No.	2131184-57-9
Formula	C₃₉H₃₉Cl₂N₅O₄
Solubility	≥125mg/mL in DMSO;insoluble in H2O
Chemical Name	3-((4R)-7-chloro-10-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-4-methyl-1-oxo-6-(1,3,5-trimethyl-1H-pyrazol-4-yl)-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-1-methyl-1H-indole-5-carboxylic acid
SDF	Download SDF
Canonical SMILES	ClC1=C(C2=C(C)N(C)N=C2C)C3=C(C(CCCOC4=CC(C)=C(Cl)C(C)=C4)=C5N3[C@H](C)CN(C6=CN(C)C7=C6C=C(C(O)=O)C=C7)C5=O)C=C1
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment [1]:
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 experiment [1]:
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
Applications	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: [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

Quality Control

Purity = 98.00%

Chemical structure

VU661013 [2131184-57-9]

Referentie A8783-5mg

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