Pinometostat (EPZ5676)
Modify Date: 2024-01-02 12:17:42
Pinometostat (EPZ5676) structure
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Common Name | Pinometostat (EPZ5676) | ||
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| CAS Number | 1380288-87-8 | Molecular Weight | 562.706 | |
| Density | 1.5±0.1 g/cm3 | Boiling Point | 835.3±75.0 °C at 760 mmHg | |
| Molecular Formula | C30H42N8O3 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | 459.0±37.1 °C | |
Use of Pinometostat (EPZ5676)Pinometostat (EPZ-5676) is a potent DOT1L histone methyltransferase inhibitor with a Ki of 80 pM. |
| Name | (2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[3-[2-(6-tert-butyl-1H-benzimidazol-2-yl)ethyl]cyclobutyl]-propan-2-ylamino]methyl]oxolane-3,4-diol |
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| Synonym | More Synonyms |
| Description | Pinometostat (EPZ-5676) is a potent DOT1L histone methyltransferase inhibitor with a Ki of 80 pM. |
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| Related Catalog | |
| Target |
Ki: < 80 pM (DOT1L histone methyltransferase) |
| In Vitro | Pinometostat (EPZ-5676) inhibits H3K79me2 with IC50 values of 3 nM and 5 nM in MV4-11 and HL60 cells, respectively. Pinometostat (EPZ-5676) is a potent inhibitor of MV4-11 proliferation with an IC50 value of 3.5 nM[1]. Pinometostat (EPZ-5676) induces a synergistic and durable antiproliferative effect, increases expression of differentiation markers and apoptosis as dingle agent, and demonstrates combination benefit in combination with AML standard of care drugs in MLL-r cells[2]. |
| In Vivo | Pinometostat (EPZ-5676) (70 mg/kg, i.p.) causes complete and sustained regression in a rat xenograft model of MLL-rearranged leukemia. Pinometostat (EPZ-5676) (70, 35 mg/kg, i.v.) reduces HOXA9 and MEIS1 mRNA levels of tumors taken from rats, and reduces MLL-fusion target gene expression in vivo[1]. |
| Cell Assay | To analyse inhibition of histone methylation in MV4-11 cells following Pinometostat treatment, extracted histones (400 ng) are fractionated on a 10-20% Tris HCl gels with Tris-Glycine SDS running buffer under denaturing conditions and transferred to nitrocellulose filters. Filters are cut into strips and incubated for 1 hour in blocking buffer at room temperature (RT) and then incubated overnight at 4°C in blocking buffer. Filters are washed 3 times for 5 minutes with wash buffer (Phosphate buffered saline (PBS) including 0.01% Tween 20 (PBST)) and incubated with infrared tagged secondary antibody at RT for 1 hour. Filters are washed in PBST and reprobed for 1 hour at RT with the appropriate total histone antibody control (mouse anti-histone H3 (1:20,000), CST 3638, or mouse anti-histone H4 (1:10,000), CST 2935). Filters are washed again in PBST and incubated with infrared tagged secondary antibody (IRDye 800Cw donkey-anti-mouse IgG (1:20,000), Li-Cor 926-32212) at RT for 1 hour. After a final ish in PBST, filters are scanned using the Odyssey infared imager (Li-cor). To analyse inhibition of H3K79 methylation in peripheral blood mononuclear cells (PBMCs) from rats dosed with Pinometostat (EPZ-5676), 20 μL of PBMC whole cell lysate is fractionated on denaturing gels and analysed by immunoblotting with antibodies to H3K79me2 or total H3. Signal intensities specific for the H3K79me2 antibody and total histone H3 control antibody are quantified using Odyssey software. The H3K79me2 signal intensity is normalized by dividing it by the total histone H3 control signal intensity in the same lane. |
| Animal Admin | 0.2 mL of a MV4-11 cell suspension (1×107 cells) in PBS is injected subcutaneously into female athymic nude mice (Crl:NU(Ncr)-Foxn1nu). Tumors are measured by calipers and mice are randomized according to tumor size into treatment groups (n=10) before the initiation of dosing with Pinometostat (EPZ-5676) when tumor volumes reache approximately 100 mma3. Pinometostat is administered intraperitoneally three times daily for 28 days at 10 and 20 mg/kg in 10% ethanol in saline. Mice are weighed and tumors measured with calipers twice weekly until the end of the study. |
| References |
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Boiling Point | 835.3±75.0 °C at 760 mmHg |
| Molecular Formula | C30H42N8O3 |
| Molecular Weight | 562.706 |
| Flash Point | 459.0±37.1 °C |
| Exact Mass | 562.338013 |
| PSA | 151.23000 |
| LogP | 4.80 |
| Vapour Pressure | 0.0±3.2 mmHg at 25°C |
| Index of Refraction | 1.722 |
| Storage condition | -20℃ |
| Pinometostat |
| 5'-[{cis-3-[2-(5-Tert-Butyl-1h-Benzimidazol-2-Yl)ethyl]cyclobutyl}(Propan-2-Yl)amino]-5'-Deoxyadenosine |
| EPZ-5676 |
| UNII-8V9YR09EF3 |
| Adenosine, 5'-deoxy-5'-[[cis-3-[2-[5-(1,1-dimethylethyl)-1H-benzimidazol-2-yl]ethyl]cyclobutyl](1-methylethyl)amino]- |
| EP6 |
| CS-1419 |
| EPZ-5676||EPZ 5676 |
| 5'-Deoxy-5'-[isopropyl(cis-3-{2-[5-(2-methyl-2-propanyl)-1H-benzimidazol-2-yl]ethyl}cyclobutyl)amino]adenosine |
| S7062 |
| EPZ5676 |