Size | Price | Stock | Qty |
---|---|---|---|
2mg |
|
||
5mg |
|
||
10mg |
|
||
25mg |
|
||
50mg |
|
||
100mg |
|
||
250mg |
|
||
Other Sizes |
|
Purity: ≥98%
Pinometostat (formerly EPZ 5676) is a potent and SAM (S-adenosyl methionine) competitive DOT1L protein methyltransferase (PMT) inhibitor with potential antitumor activity. It inhibits DOT1L with a Ki of 80 pM in a cell-free assay, and exhibits >37,000-fold higher selectivity for DOT1L over other PMTs. It exhibits excellent antiproliferative activity and high in vivo antitumor efficacy.
ln Vitro |
For MV4-11 and HL60 cells, respectively, pinometostat (EPZ-5676) has an IC50 value of 3 nM and 5 nM for inhibiting H3K79me2. Pinometostat, also known as EPZ-5676, has an IC50 value of 3.5 nM, making it a strong inhibitor of MV4-11 proliferation(1). In MLL-r cells, pinometostat (EPZ-5676) exhibits cooperative benefits when used in conjunction with AML treatment medications. It also has synergistic and durable antiproliferative effects, upregulating the expression of differentiation markers and apoptosis by itself [2].
|
||
---|---|---|---|
ln Vivo |
In a rat xenograft model of MLL-rearranged leukemia, pinometostat (EPZ-5676) (70 mg/kg, ip) results in total and sustained regression. Rat tumors grown from HOXA9 and MEIS1 mRNA levels are decreased by pinometostat (EPZ-5676) (70, 35 mg/kg, iv), which also lowers MLL fusion target gene expression in vivo [1].
|
||
Animal Protocol |
|
||
References |
[1]. Daigle SR, et al. Potent inhibition of DOT1L as treatment for MLL-fusion leukemia. Blood. 2013 Jun 25. [Epub ahead of print]
[2]. Klaus CR, et al. DOT1L inhibitor EPZ-5676 displays synergistic antiproliferative activity in combination with standard of care drugs and hypomethylating agents in MLL-rearranged leukemia cells. J Pharmacol Exp Ther. 2014 Sep;350(3):646-56 |
Molecular Formula |
C30H42N8O3
|
|
---|---|---|
Molecular Weight |
562.71
|
|
CAS # |
1380288-87-8
|
|
Related CAS # |
|
|
SMILES |
O[C@H]1[C@H](N2C=NC3=C(N)N=CN=C23)O[C@H](CN([C@H]4C[C@@H](CCC5=NC6=CC(C(C)(C)C)=CC=C6N5)C4)C(C)C)[C@H]1O
|
|
InChi Key |
LXFOLMYKSYSZQS-LURJZOHASA-N
|
|
InChi Code |
InChI=1S/C30H42N8O3/c1-16(2)37(13-22-25(39)26(40)29(41-22)38-15-34-24-27(31)32-14-33-28(24)38)19-10-17(11-19)6-9-23-35-20-8-7-18(30(3,4)5)12-21(20)36-23/h7-8,12,14-17,19,22,25-26,29,39-40H,6,9-11,13H2,1-5H3,(H,35,36)(H2,31,32,33)/t17-,19+,22-,25-,26-,29-/m1/s1
|
|
Chemical Name |
(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
|
|
Synonyms |
EPZ 5676; Pinometostat; EPZ-5676; EPZ5676
|
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
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) |
|
|||
---|---|---|---|---|
Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.44 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 (4.44 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 (4.44 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: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% EtOH + 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 EtOH stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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 5: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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. Solubility in Formulation 6: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (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 EtOH stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 7: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O:5mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7771 mL | 8.8856 mL | 17.7711 mL | |
5 mM | 0.3554 mL | 1.7771 mL | 3.5542 mL | |
10 mM | 0.1777 mL | 0.8886 mL | 1.7771 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT03701295 | Completed Has Results | Drug: Azacitidine Drug: Pinometostat |
Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia |
National Cancer Institute (NCI) | March 6, 2020 | Phase 1 Phase 2 |
NCT03724084 | Terminated | Drug: Daunorubicin Hydrochloride Drug: Pinometostat |
Acute Myeloid Leukemia | National Cancer Institute (NCI) | January 25, 2019 | Phase 1 Phase 2 |