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Chemical Structure| 1380288-87-8 Chemical Structure| 1380288-87-8

Structure of Pinometostat
CAS No.: 1380288-87-8

Chemical Structure| 1380288-87-8

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Pinometostat (EPZ-5676) is an extremely potent inhibitor of DOT1L histone methyltransferase, exhibiting a Ki of 80 pM.

Synonyms: EPZ-5676

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Product Details of Pinometostat

CAS No. :1380288-87-8
Formula : C30H42N8O3
M.W : 562.71
SMILES Code : NC1=NC=NC2=C1N=CN2[C@H]3[C@H](O)[C@H](O)[C@@H](CN([C@@H]4C[C@H](CCC5=NC6=C(C=CC(C(C)(C)C)=C6)N5)C4)C(C)C)O3
Synonyms :
EPZ-5676
MDL No. :MFCD24849416
InChI Key :LXFOLMYKSYSZQS-XKHGBIBOSA-N
Pubchem ID :57345410

Safety of Pinometostat

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Pinometostat

epigenetics

Isoform Comparison

Biological Activity

Target
  • Histone Methyltransferase

    DOT1L, Ki:80 pM

In Vitro:

Cell Line
Concentration Treated Time Description References
human lung epithelial cells A549 1 μM 48 hours To investigate the effect of Pinometostat on interferon signaling, results showed that Pinometostat significantly decreased luciferase accumulation in infected cells, reinforcing the role of DOT1L in controlling interferon signaling. PMC6856118
MV4-11 1 µM 8 days Inhibited cell proliferation, IC50 value below 1 µM PMC7409321
MOLM-13 1 µM 8 days Inhibited cell proliferation, IC50 value below 1 µM PMC7409321
NOMO-1 1 µM 8 days Inhibited cell proliferation, IC50 value below 1 µM PMC7409321
OCI-AML3 1 µM 8 days Inhibited cell proliferation PMC7409321
MV4;11 10-500 nM 7 days To determine the effect of low-dose Pinometostat on MV4;11 cell proliferation and global H3K79me2 levels. Results showed that 10 nM Pinometostat significantly reduced global H3K79me2 levels and decreased MV4;11 proliferation by 30 ±10%, while 100 nM inhibitor reduced cell proliferation by 80 ±10%. PMC8315800
MV4;11 100 nM 7 days To determine the effect of Pinometostat on MV4;11 gene expression through RNA-seq analysis. Results showed that 1916 genes were downregulated and 2007 genes were upregulated. PMC8315800
MV4-11 cells 10 µM, 3.2 µM, 1 µM 15 days Evaluate the effect of Pinometostat on the proliferation and viability of MV4-11 cells, results show that Pinometostat inhibits cell proliferation without affecting cell viability, showing a cytostatic effect PMC8434109
MOLM-13 cells 3.2 µM, 1 µM, 0.32 µM 15 days Evaluate the effect of Pinometostat on the proliferation and viability of MOLM-13 cells, results show that Pinometostat can persistently and significantly inhibit cell proliferation at low concentrations PMC8434109
KOPN8 cells 10 µM, 3.2 µM, 1 µM 22 days Evaluate the effect of Pinometostat on the proliferation and viability of KOPN8 cells, results show that Pinometostat inhibits cell proliferation without affecting cell viability, showing a cytostatic effect PMC8434109
GO orbital fibroblasts 4.5 µM 24 hours Inhibited PDGF-BB-induced orbital fibroblast proliferation and hyaluronan production PMC10994939
SEM cells 1 to 100 µM 14 weeks To induce acquired resistance to Pinometostat in SEM and RS4;11 cells, results showed that after 14 weeks of gradually increasing concentrations of Pinometostat treatment, the cells developed significant resistance to the drug. PMC10517487
RS4;11 cells 1 to 100 µM 14 weeks To induce acquired resistance to Pinometostat in RS4;11 cells, results showed that after 14 weeks of gradually increasing concentrations of Pinometostat treatment, the cells developed significant resistance to the drug. PMC10517487

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice MLL-r leukemia xenograft model Intraperitoneal injection 10 mg/kg Every 3 days for 7 times Pinometostat showed antitumor activity in MLL-r leukemia xenograft models, reducing leukemia cell growth, and no tumor regrowth was observed for over 30 days beyond cessation of treatment. PMC7188393

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01684150 Acute Myeloid Leukemia|Acute L... More >>ymphoblastic Leukemia|Myelodysplastic Syndrome|Myeloproliferative Disorders Less << PHASE1 COMPLETED 2025-02-16 Mayo Clinic Scottsdale-Phoenix... More >>, Scottsdale, Arizona, 85259, United States|Northwestern University, Chicago, Illinois, 60611, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|Duke University Health System, Durham, North Carolina, 27710, United States|Sarah Cannon Research Institute, Nashville, Tennessee, 37203, United States|UT MD Anderson Cancer, Houston, Texas, 77030, United States|Universit?tsklinikum Ulm, Ulm, 89081, Germany|Erasmus University Medical Center, Rotterdam, Netherlands Less <<
NCT02141828 Leukemia|Acute Myeloid Leukemi... More >>a|Acute Lymphocytic Leukemia|Acute Leukemias Less << PHASE1 COMPLETED 2025-06-16 Childrens Hospital Los Angeles... More >>, Los Angeles, California, 90027, United States|University of California San Francisco Medical Center-Parnassus, San Francisco, California, 94143, United States|Children's Hospital Colorado, Aurora, Colorado, 80045, United States|Emory Children's Healthcare of Atlanta, Atlanta, Georgia, 30322, United States|Johns Hopkins University, Baltimore, Maryland, 21287, United States|Dana Farber Cancer Institute, Boston, Massachusetts, 02215, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229, United States|The Hospital for Sick Kids, Toronto, Ontario, Canada Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.78mL

0.36mL

0.18mL

8.89mL

1.78mL

0.89mL

17.77mL

3.55mL

1.78mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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