VU0661013

Name: VU0661013
Brand: MedChemExpress
SKU: HY-112859
Rating: 4.5 (1 reviews)

Cat. No.: HY-112859 Purity: 98.45%: FAQs
Data Sheet SDS COA Handling Instructions

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VU661013 is a potent and selective MCL-1 inhibitor.

For research use only. We do not sell to patients.

VU0661013 Chemical Structure

CAS No. : 2131184-57-9

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 495	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 495	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 450	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 670	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 1060	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 1430	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 1920	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Based on 1 publication(s) in Google Scholar

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Bcl-2 Bcl-xL Bcl-W Mcl-1 Bfl-1 Bcl-B Bax Bak Bim

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

VU661013 is a potent and selective MCL-1 inhibitor.

IC₅₀ & Target^[1]

Mcl-1

Cellular Effect

Cell Line	Type	Value	Description	References
AMO1	GI₅₀	140 nM Compound: 42; VU0661013	Antiproliferative activity against Mcl1-sensitive human AMO1 cells assessed as cell growth inhibition measured after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against Mcl1-sensitive human AMO1 cells assessed as cell growth inhibition measured after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
B-ALL	IC₅₀	1600 nM Compound: 42; VU0661013	Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human BFL1 assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human BFL1 assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis	[PMID: 30929420]
B-ALL	IC₅₀	2208 nM Compound: 42; VU0661013	Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human Bcl2 assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human Bcl2 assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis	[PMID: 30929420]
B-ALL	IC₅₀	2856 nM Compound: 42; VU0661013	Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human BFL-w assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human BFL-w assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis	[PMID: 30929420]
B-ALL	IC₅₀	3895 nM Compound: 42; VU0661013	Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human Bcl-xl assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human Bcl-xl assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis	[PMID: 30929420]
B-ALL	IC₅₀	4186 nM Compound: 42; VU0661013	Antiproliferative activity against BCR-ABL-positive double bax/bak knockout human B-ALL cells assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis Antiproliferative activity against BCR-ABL-positive double bax/bak knockout human B-ALL cells assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis	[PMID: 30929420]
B-ALL	IC₅₀	446 nM Compound: 42; VU0661013	Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human MCl1 assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis Antiproliferative activity against BCR-ABL positive human B-ALL cells expressing human MCl1 assessed as reduction in cell viability after 24 hrs by Annexin-V-APC/propidium iodide staining-based flow cytometric analysis	[PMID: 30929420]
BT-20	GI₅₀	2.1 μM Compound: 42; VU0661013	Antiproliferative activity against human BT20 cells assessed as cell growth inhibition measured after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against human BT20 cells assessed as cell growth inhibition measured after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
HCC1187	GI₅₀	1.3 μM Compound: 42; VU0661013	Antiproliferative activity against human HCC1187 cells assessed as cell growth inhibition measured after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against human HCC1187 cells assessed as cell growth inhibition measured after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
K562	GI₅₀	9.2 μM Compound: P-42	Antiproliferative activity against Mcl1-insensitive human K562 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against Mcl1-insensitive human K562 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
K562	GI₅₀	9.2 μM Compound: M-42	Antiproliferative activity against Mcl1-insensitive human K562 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against Mcl1-insensitive human K562 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
K562	GI₅₀	9.3 μM Compound: 42; VU0661013	Antiproliferative activity against Mcl1-insensitive human K562 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against Mcl1-insensitive human K562 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
MV4-11	GI₅₀	181 nM Compound: VU661013	Antiproliferative activity against human MV4-11 cells assessed as cell growth inhibition incubated for 48 hrs by CellTiter-Glo reagent based assay Antiproliferative activity against human MV4-11 cells assessed as cell growth inhibition incubated for 48 hrs by CellTiter-Glo reagent based assay	[PMID: 33253879]
MV4-11	GI₅₀	70 nM Compound: 42; VU0661013	Antiproliferative activity against Mcl1-sensitive human MV4-11 cells assessed as cell growth inhibition measured after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against Mcl1-sensitive human MV4-11 cells assessed as cell growth inhibition measured after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
NCI-H929	EC₅₀	0.11 μM Compound: M-42	Induction of apoptosis in Mcl-1 sensitive human NCI-H929 cells assessed as activation of caspase3/7 for 3 hrs by Caspase-Glo luminescence analysis Induction of apoptosis in Mcl-1 sensitive human NCI-H929 cells assessed as activation of caspase3/7 for 3 hrs by Caspase-Glo luminescence analysis	[PMID: 30929420]
NCI-H929	GI₅₀	0.12 μM Compound: P-42	Antiproliferative activity against Mcl1-sensitive human NCI-H929 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against Mcl1-sensitive human NCI-H929 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
NCI-H929	GI₅₀	0.12 μM Compound: M-42	Antiproliferative activity against Mcl1-sensitive human NCI-H929 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against Mcl1-sensitive human NCI-H929 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
NCI-H929	EC₅₀	0.13 μM Compound: P-42	Induction of apoptosis in Mcl-1 sensitive human NCI-H929 cells assessed as activation of caspase3/7 for 3 hrs by Caspase-Glo luminescence analysis Induction of apoptosis in Mcl-1 sensitive human NCI-H929 cells assessed as activation of caspase3/7 for 3 hrs by Caspase-Glo luminescence analysis	[PMID: 30929420]
NCI-H929	EC₅₀	0.16 μM Compound: 42; VU0661013	Induction of apoptosis in Mcl-1 sensitive human NCI-H929 cells assessed as activation of caspase3/7 for 3 hrs by Caspase-Glo luminescence analysis Induction of apoptosis in Mcl-1 sensitive human NCI-H929 cells assessed as activation of caspase3/7 for 3 hrs by Caspase-Glo luminescence analysis	[PMID: 30929420]
NCI-H929	GI₅₀	0.19 μM Compound: 42; VU0661013	Antiproliferative activity against Mcl1-sensitive human NCI-H929 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay Antiproliferative activity against Mcl1-sensitive human NCI-H929 cells assessed as cell growth inhibition after 72 hrs by Celltiter-glo luminescence assay	[PMID: 30929420]
NCI-H929	EC₅₀	100 nM Compound: 42; VU0661013	Induction of apoptosis in Mcl1-sensitive human NCI-H929 cells measured after 3 hrs by Caspase-glo luminescence analysis Induction of apoptosis in Mcl1-sensitive human NCI-H929 cells measured after 3 hrs by Caspase-glo luminescence analysis	[PMID: 30929420]

In Vitro

VU661013 exhibits a K_i of 97±30 pM to human MCL-1 in a TR-FRET assay by displacing a fluorescently labeled peptide derived from the pro-apoptotic protein BAK. However, VU661013 does not significantly inhibit BCL-xL (K_i>40 μM) or BCL-2 (K_i=0.73 μM)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

VU661013, 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 and patient derived xenografts. After establishing disseminated leukemia, NSGS mice are dosed intraperitoneally with 10, 25 or 75 mg/kg of VU661013 daily for 21 days. Weekly chimerism analyses are conducted and the percentage of MV-4-11 cells are quantified in murine peripheral blood using anti-human CD45 (hCD45) and anti-hCD33 monoclonal antibodies. Twenty-eight days post-transplant, vehicle-treated mice have developed large leukemia burdens and thus, mice are sacrificed, and their organs are harvested for analysis. Vehicle mice treated died of xenografted AML, but have no evidence of VU661013-related toxicity in non target organs. VU661013 treatment of disseminated human AML results in a dose-dependent decrease in tumor burden, nearly eliminating the hCD45⁺ MV-4-11 cells at the 75 mg/kg dose in the blood (mean, 13.0±2.2% in vehicle vs 7.4±7.2% in 25mg/kg vs 0.17±0.12% in 75 mg/kg treated mice), bone marrow (mean, 40.7±13.9% in vehicle vs 33.46±4.0 % in 25 mg/kg vs 0.384±0.345 in 75 mg/kg treated mice), and spleen (mean, 46.22±13.3% in vehicle vs 13.31±10.0% in 25 mg/kg vs 1.588±1.51% in 75 mg/kg treated mice). Treatment with VU661013 reduces disease-associated splenomegaly (mean, vehicle vs. 75mg/kg, 0.17±0.02 vs 0.09±0.01g), and amendeding spleen to body weight ratio (vehicle vs 75mg/kg, 0.99 vs 0.50). In a second MV-4-11 xenograft study, mice are followed until death, and survival is evaluated by Kaplan-Meier analysis. In this study, NSGS mice are treated daily (starting 7 days after transplant) with vehicle only, 15 mg/kg or 75 mg/kg of VU661013. Analysis reveals an increase in survival in mice treated with the 75mg/kg dose (vehicle treated mice=31 days, vs 15 mg/kg=32 days, vs 75 mg/kg treated mice=43 Days)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

712.66

Formula

C₃₉H₃₉Cl₂N₅O₄

CAS No.

2131184-57-9

Appearance

Solid

Color

Light yellow to yellow

SMILES

ClC1=CC=C(C(CCCOC2=CC(C)=C(Cl)C(C)=C2)=C3N4[C@H](C)CN(C5=CN(C)C6=C5C=C(C(O)=O)C=C6)C3=O)C4=C1C7=C(C)N(C)N=C7C

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : ≥ 125 mg/mL (175.40 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.4032 mL	7.0160 mL	14.0319 mL
5 mM	0.2806 mL	1.4032 mL	2.8064 mL
10 mM	0.1403 mL	0.7016 mL	1.4032 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (2.92 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.08 mg/mL (2.92 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.08 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (2.92 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 98.45%

Select Batch:

Data Sheet (281 KB) SDS (393 KB)

COA (261 KB) LCMS (97 KB)

Handling Instructions (2659 KB)

References

[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.

Cell Assay ^[1]	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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[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.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.4032 mL	7.0160 mL	14.0319 mL	35.0798 mL
	5 mM	0.2806 mL	1.4032 mL	2.8064 mL	7.0160 mL
	10 mM	0.1403 mL	0.7016 mL	1.4032 mL	3.5080 mL
	15 mM	0.0935 mL	0.4677 mL	0.9355 mL	2.3387 mL
	20 mM	0.0702 mL	0.3508 mL	0.7016 mL	1.7540 mL
	25 mM	0.0561 mL	0.2806 mL	0.5613 mL	1.4032 mL
	30 mM	0.0468 mL	0.2339 mL	0.4677 mL	1.1693 mL
	40 mM	0.0351 mL	0.1754 mL	0.3508 mL	0.8770 mL
	50 mM	0.0281 mL	0.1403 mL	0.2806 mL	0.7016 mL
	60 mM	0.0234 mL	0.1169 mL	0.2339 mL	0.5847 mL
	80 mM	0.0175 mL	0.0877 mL	0.1754 mL	0.4385 mL
	100 mM	0.0140 mL	0.0702 mL	0.1403 mL	0.3508 mL

VU0661013 Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

VU06610132131184-57-9VU 0661013VU-0661013Bcl-2 FamilyInhibitorinhibitorinhibit

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VU0661013

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Complete Stock Solution Preparation Table

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