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VTP50469

Catalog No.GC61376

VTP50469 is a small-molecule inhibitor of the Menin-MLL protein-protein interaction with a Ki of 104 pM.

Products are for research use only. Not for human use. We do not sell to patients.

VTP50469 Chemical Structure

Cas No.: 2169916-18-9

Size Price Stock Qty
10mM (in 1mL DMSO)
$337.00
In stock
5mg
$80.00
In stock
10mg
$128.00
In stock
50mg
$384.00
In stock
100mg
$614.00
In stock
200mg
$982.00
In stock
500mg
$1,842.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

MOLM13 cells, RS4;11 lymphoblast cells

Preparation Method

Cells are treated for 2 and 7 days with VTP50469 or DMSO followed by RNA-seq analysis.

Reaction Conditions

330 nM; 2 and 7 days

Applications

VTP50469 treatment leads to rapid downregulation of MLL fusion-driven gene expression.

Animal experiment [2]:

Animal models

Female NSG mice(7-9 week-old)

Preparation Method

The mice(carrying MV4;11-FUW-Luc-mCh-Puro cells ) were randomized into four treatment groups (n=10) based on body weight. The groups included a vehicle control and three VTP50469 groups (15, 30, 60 mg/kg BID). Treatment began on day 5 and continued for 28 days.

Dosage form

15 /30 /60mg/kg;p.o.;23days

Applications

VTP50469 treatment(30 and 60 mg/kg) had a surprisingly extended survival advantage in mice.

References:

[1]. Krivtsov AV, Evans K, et,al. A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia. Cancer Cell. 2019 Dec 9;36(6):660-673.e11. doi: 10.1016/j.ccell.2019.11.001. PMID: 31821784; PMCID: PMC7227117.

Background

VTP50469 is a small-molecule inhibitor of the Menin-MLL protein-protein interaction with a Ki of 104 pM. VTP50469 has potently anti-leukemia activity[1-4].

VTP50469 led to a profound reduction in cell proliferation in a concentrationdependent manner in MLL-r cell lines, besides, VTP50469 treatment(330 nM; 2 and 7 days) leads to rapid downregulation of MLL fusion-driven gene expression[3].

VTP50469 (30 and 60 mg/kg;p.o.;23days) had a surprisingly extended survival advantage in MLL-r Acute Leukemia patient-derived xenograft (PDX) mice[3]. Treatment with VTP50469 significantly prolongs survival of mice engrafted with NUP98-NSD1 and NUP98-JARID1A leukemias[5].

References:
[1]. Ishchenko A, Liu Z, et al.Structure-based design technology contour and its application to the design of renin inhibitors. J Chem Inf Model. 2012 Aug 27;52(8):2089-97. doi: 10.1021/ci200605k. Epub 2012 Jul 25. PMID: 22805048.
[2].Janssens DH, Meers MP, et al. Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia. Nat Genet. 2021 Nov;53(11):1586-1596. doi: 10.1038/s41588-021-00941-9. Epub 2021 Oct 18. PMID: 34663924; PMCID: PMC8571097.
[3]. Krivtsov AV, Evans K, et al. A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia. Cancer Cell. 2019 Dec 9;36(6):660-673.e11. doi: 10.1016/j.ccell.2019.11.001. PMID: 31821784; PMCID: PMC7227117.
[4]. Andrei V. Krivtsov, et al. Abstract 4958: VTP50469 is a novel, orally available menin-MLL1 inhibitor effective against MLL-rearranged and NPM1-mutant leukemia. Cancer Resceach. July 2018.Volume 78, Issue 13 Supplement.
[5]. Heikamp EB, Henrich JA, et al. The menin-MLL1 interaction is a molecular dependency in NUP98-rearranged AML. Blood. 2022 Feb 10;139(6):894-906. doi: 10.1182/blood.2021012806. PMID: 34582559; PMCID: PMC8832476.

Chemical Properties

Cas No. 2169916-18-9 SDF
Canonical SMILES O=C(N(C(C)C)C(C)C)C1=CC(F)=CC=C1OC2=CN=CN=C2N3CC4(CCN(C[C@H]5CC[C@H](NS(=O)(C)=O)CC5)CC4)C3
Formula C32H47FN6O4S M.Wt 630.82
Solubility DMSO: 125 mg/mL (198.15 mM) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 1.5852 mL 7.9262 mL 15.8524 mL
5 mM 0.317 mL 1.5852 mL 3.1705 mL
10 mM 0.1585 mL 0.7926 mL 1.5852 mL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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Average Rating: 5 ★★★★★ (Based on Reviews and 8 reference(s) in Google Scholar.)

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