VTP50469

SKU: orb1308940

Description

VTP50469 is a potent, orally bioavailable small molecule that selectively inhibits the Menin-MLL interaction with sub-nanomolar affinity (Ki = 104 pM). It demonstrates robust anti-leukemic efficacy in both cellular assays and in vivo models, making it a valuable chemical probe for researching MLL-rearranged and NPM1-mutant leukemias.

Research Area

Cell Biology, Epigenetics & Chromatin

Key Properties

• CAS Number: 2169916-18-9
• MW: 630.82
• Purity: 98.31%
• Formula: C₃₂H₄₇FN₆O₄S
• SMILES: CC(C)N(C(C)C)C(=O)c1cc(F)ccc1Oc1cncnc1N1CC2(C1)CCN(C[C@H]1CC[C@@H](CC1)NS(C)(=O)=O)CC2
• Target: Epigenetic Reader Domain,Histone Methyltransferase,Apoptosis
• Solubility: DMSO:125 mg/mL (198.15 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (6.34 mM)

Bioactivity

• Target IC50:
  Menin-MLL:ki:104 pM
• In Vivo:
  METHODS: MV4-transplanted NSG mice were treated with VTP50469 (15, 30, and 60 mg/kg, orally twice a day) and the tumor growth in vivo was observed. RESULTS The size of subcutaneous tumors in mice decreased in a dose-dependent manner.
• In Vitro:
  VTP50469 inhibits cell proliferation in a concentration-dependent manner in MLL-r cell lines, including (MOLM13 with IC50 of 13 nM), THP1 (IC50 of 37 nM), NOMO1 (IC50 of 30 nM), ML2 (IC50 of 16 nM), EOL1 (IC50 of 20 nM), and murine MLL-AF9 cells (IC50 of 15 nM)), as well as ALL cell lines (KOPN8 (IC50 of 15 nM), HB11;19 (IC50 of 36 nM), MV4;11 (IC50 of 17 nM), SEMK2 (IC50 of 27 nM), and RS4;11 (IC50 of 25 nM)). At early timepoints, MLL-r B cell ALL (B-ALL) cell lines, but not MLL-r AML cell lines, underwent dose-dependent apoptosis in response to VTP50469, while MLL-r AML cell lines exhibited dose-dependent differentiation starting at 4-6 days of exposure. VTP50469 displaces Menin from protein complexes, reducing MLL chromatin occupancy on certain genes, resulting in altered gene expression, differentiation, and apoptosis .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Epigenetic Reader Domain, EpigeneticReaderDomain, Menin-MLL, Menin-MLL interaction, leukemia, Histone Methyltransferase, HistoneMethyltransferase, Inhibitor, differentiation, antiproliferative, Apoptosis, survival, protein-protein, VTP 50469, VTP50469, VTP-50469

Compound Identifiers

PubChem CID

132212900