VTP50469 |
Katalog-Nr.GC61376
One-Click Copy Product Info
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VTP50469 ist ein niedermolekularer Inhibitor der Menin-MLL-Protein-Protein-Interaktion mit einem Ki-Wert von 104 pM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2169916-18-9
Sample solution is provided at 25 µL, 10mM.
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VTP50469 ist ein niedermolekularer Inhibitor der Menin-MLL-Protein-Protein-Interaktion mit einem Ki-Wert von 104 pM. VTP50469 hat eine starke Anti-Leukämie-Aktivität[1-4].
VTP50469 führte in MLL-r-Zelllinien zu einer deutlichen, konzentrationsabhängigen Reduktion der Zellproliferation. Außerdem bewirkte die Behandlung mit VTP50469(330 nM; 2 znd 7 Tage) eine rasche Herunterregulierung der MLL-Fusionsgen-Expression[3].
VTP50469 (30 und 60 mg/kg; p.o.; 23 Tage)zeigte einen überraschend verlängerten Überlebensvorteil in MLL-r-akuten Leukämie-Patienten-abgeleiteten Xenograft-Mäusen(PDX)[3]. Die Behandlung mit VTP50469 verlängert das Überleben von Mäusen, denen NUP98-NSD1- und NUP98-JARID1A-Leukämien transplantiert wurden, erheblich[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.
| Zellexperiment [1]: | |
Zelllinien | MOLM13-Zellen, RS4; 11-Lymphoblastenzellen |
Vorbereitungsmethode | Die Zellen wurden 2 bzw. 7 Tage lang mit VTP50469 oder DMSO behandelt, gefolgt von einer RNA-seq-Analyse. |
Reaktionsbedingungen | 330 nM; 2 und 7 Tagen |
Anwendungen | Die Behandlung mit VTP50469 führte zu einer schnellen Herunterregulierung der MLL-Fusionsgen-Expression. |
| Tierversuch [2]: | |
Tiermodelle | Weibliche NSG-Mäuse(7-9 Wochen alt) |
Vorbereitungsmethode | Die Mäuse(mit MV4; 11-FUW-Luc-mCh-Puro-Zellen) wurden anhand ihres Körpergewichts randomisiert in 4 Behandlungsgruppen(n=10) eingeteilt. Die Gruppen umfassten eine Vehikelkontrolle und 3 VTP50469-Gruppen(15, 30, 60 mg/kg zweimal täglich(BID)). Die Behandlung begann an Tag 5 und dauerte 28 Tage. |
Dosierungsform | 15 /30 /60mg/kg; p.o.; 23 Tage |
Anwendungen | Die Behandlung mit VTP50469(30 und 60 mg/kg) führte bei Mäusen zu einem überraschend lang anhaltenden Überlebensvorteil. |
References: | |
| 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 |
| Löslichkeit | 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5852 mL | 7.9262 mL | 15.8524 mL |
| 5 mM | 317 μL | 1.5852 mL | 3.1705 mL |
| 10 mM | 158.5 μL | 792.6 μL | 1.5852 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
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 saline, 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.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)