| Size | Price | |
|---|---|---|
| 10mg | ||
| Other Sizes |
VTP50469 fumarate, the fumarate salt of VTP50469 (VTP-50469), is an orally bioavailable inhibitor of Menin-MLL interaction (Ki = 104 pM) with potential antineoplastic activity.
| ln Vitro |
VTP50469 exhibits activity in cells containing the following: mouse MLL-AF9 cells (IC50 = 15 nM), ALL (KOPN8 (IC50 = 15 nM), HB11;19 (IC50 = 36 nM), MV4;11 (IC50 = 17 nM), SEMK2 (IC50 = 27 nM), and RS4;11 (IC50 = 25 nM)) cell line. Early on, MLL-r B-cell ALL (B-ALL) cell lines respond to VTP50469. They experience dose-dependent apoptosis, but not MLL-r AML cell lines. Four to six days after being exposed to VTP50469, MLL-r AML cell lines start to differentiate in a dose-dependent manner [1]. Menin is replaced by VTP50469 in protein complexes, and it prevents MLL from occupying certain genes' chromatin. Apoptosis, differentiation, and gene expression are all altered by loss of MLL binding [1].
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|---|---|
| ln Vivo |
The VTP50469 (15–60 mg/kg) oral medication administered twice daily for 28 days to NSG mice was very effective at all dose levels and significantly increased survival in all treatment groups. VTP50469 dosages of 30 and 60 mg/kg provided mice with a sustained survival benefit [1].
|
| Animal Protocol |
Animal/Disease Models: Non-Conditioned Immunodeficient (NSG) Mice with MV4; 11 cells[1]
Doses: 15 mg/kg, 30 mg/kg, and 60 mg/kg Route of Administration: Oral; :Oral administration. twice (two times) daily; for 28 days Experimental Results: Highly effective at all dose levels, and all treatment groups had a significant survival advantage over the control group. |
| References |
|
| Molecular Formula |
C32H47FN6O4S.3/2C4H4O4
|
|---|---|
| Molecular Weight |
746.90
|
| Exact Mass |
1608.705
|
| CAS # |
2169919-29-1
|
| Related CAS # |
VTP50469;2169916-18-9
|
| PubChem CID |
168012211
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
8
|
| Hydrogen Bond Acceptor Count |
32
|
| Rotatable Bond Count |
26
|
| Heavy Atom Count |
112
|
| Complexity |
1160
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C([C@H]1CC[C@H](NS(=O)(=O)C)CC1)N1CCC2(CN(C3=NC=NC=C3OC3C=CC(F)=CC=3C(=O)N(C(C)C)C(C)C)C2)CC1.C(/C(=O)O)=C\C(=O)O
|
| InChi Key |
DGSSIIRNGCQGQL-VQYXCCSOSA-N
|
| InChi Code |
InChI=1S/2C32H47FN6O4S.3C4H4O4/c2*1-22(2)39(23(3)4)31(40)27-16-25(33)8-11-28(27)43-29-17-34-21-35-30(29)38-19-32(20-38)12-14-37(15-13-32)18-24-6-9-26(10-7-24)36-44(5,41)42;3*5-3(6)1-2-4(7)8/h2*8,11,16-17,21-24,26,36H,6-7,9-10,12-15,18-20H2,1-5H3;3*1-2H,(H,5,6)(H,7,8)/b;;3*2-1+
|
| Chemical Name |
(E)-but-2-enedioic acid;5-fluoro-2-[4-[7-[[4-(methanesulfonamido)cyclohexyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]pyrimidin-5-yl]oxy-N,N-di(propan-2-yl)benzamide
|
| Synonyms |
VTP 50469 fumarate VTP-50469 fumarate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~124.23 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.11 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 13.33 mg/mL (16.56 mM) in 0.5% Hypromellose (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3389 mL | 6.6943 mL | 13.3887 mL | |
| 5 mM | 0.2678 mL | 1.3389 mL | 2.6777 mL | |
| 10 mM | 0.1339 mL | 0.6694 mL | 1.3389 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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