CONTACT US
Home > Inhibitors/Agonists> > EPZ-5676
EPZ-5676

EPZ-5676

  • CAT Number: I001465
  • CAS Number: 1380288-87-8
  • Molecular Formula: C₃₀H₄₂N₈O₃
  • Molecular Weight: 562.71
  • Purity: ≥95%
Inquiry Now

<p style=/line-height:25px/>EPZ-5676 is a potent and selective aminonucleoside inhibitor of DOT1L histone methyltransferase with Ki of 80 pM; demonstrating >37,000-fold selectivity against all other PMTs tested, inhibits H3K79 methylation in tumor.<br>IC50 Value: 80 pM (Ki value) [1]<br>Target:<br>in vitro: The compound has a Ki value of 80 pM, and demonstrates 37,000-fold selectivity over all other methyltransferases tested. In cellular studies, EPZ-5676inhibited H3K79 methylation and MLL-fusion target gene expression and demonstrated potent cell killing that was selective for acute leukemia lines bearing MLL translocations [1].<br>in vivo: Continuous intravenous (IV) infusion of EPZ-5676 in a rat xenograft model of MLL-rearranged leukemia caused complete tumor regressions that were sustained well beyond the compound infusion period with no significant weight loss or signs of toxicity [1].<br>Clinical trial: A First-in-Human, Phase I and Expanded Cohort Study of EPZ-5676 in Advanced Hematological Malignancies, Including Acute Leukemia With Rearrangement of the MLL Gene. Phase 1<br></p>

Catalog Number I001465
CAS Number 1380288-87-8
Molecular Formula

C₃₀H₄₂N₈O₃

Purity 95%
Target Histone Methyltransferase
Solubility DMSO: ≥ 47.8 mg/mL
Storage 3 years -20C powder
IC50 80 pM (Ki value) [1]
InChI 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-/
InChIKey LXFOLMYKSYSZQS-LURJZOHASA-N
SMILES CC(C)(C)C1=CC2=C(NC(CC[[email protected]]3C[[email protected]@H](N(C[[email protected]@H]4[[email protected]@H](O)[[email protected]@H](O)[[email protected]](N5C(N=CN=C6C6N)=C6N=C5)O4)C(C)C)C3)=N2)C=C1
Reference

</br>1:Mechanisms of Pinometostat (EPZ-5676) Treatment Emergent Resistance in MLL Rearranged Leukemia. Campbell CT, Haladyna JN, Drubin DA, Thomson TM, Maria MJ, Yamauchi T, Waters NJ, Olhava EJ, Pollock RM, Smith JJ, Copeland RA, Blakemore SJ, Bernt KM, Daigle SR.Mol Cancer Ther. 2017 Apr 20. pii: molcanther.0693.2016. doi: 10.1158/1535-7163.MCT-16-0693. [Epub ahead of print] PMID: 28428443 </br>2:Preclinical Pharmacokinetics and Pharmacodynamics of Pinometostat (EPZ-5676), a First-in-Class, Small Molecule S-Adenosyl Methionine Competitive Inhibitor of DOT1L. Waters NJ.Eur J Drug Metab Pharmacokinet. 2017 Feb 22. doi: 10.1007/s13318-017-0404-3. [Epub ahead of print] PMID: 28229434 </br>3:[Mechanism of A New DOT1L Inhibitor EPZ-5676 and Its Research Progress -Review]. Li LH, Wang J, Ke XY.Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Dec;24(6):1909-1912. doi: 10.7534/j.issn.1009-2137.2016.06.055. Chinese. PMID: 28024519 </br>4:Metabolism and disposition of the DOT1L inhibitor, pinometostat (EPZ-5676), in rat, dog and human. Waters NJ, Smith SA, Olhava EJ, Duncan KW, Burton RD, O/’Neill J, Rodrigue ME, Pollock RM, Moyer MP, Chesworth R.Cancer Chemother Pharmacol. 2016 Jan;77(1):43-62. doi: 10.1007/s00280-015-2929-y. Epub 2015 Dec 8. PMID: 26645404 </br>5:Exploring drug delivery for the DOT1L inhibitor pinometostat (EPZ-5676): Subcutaneous administration as an alternative to continuous IV infusion, in the pursuit of an epigenetic target. Waters NJ, Daigle SR, Rehlaender BN, Basavapathruni A, Campbell CT, Jensen TB, Truitt BF, Olhava EJ, Pollock RM, Stickland KA, Dovletoglou A.J Control Release. 2015 Dec 28;220(Pt B):758-65. doi: 10.1016/j.jconrel.2015.09.023. Epub 2015 Sep 15. PMID: 26385168 </br>6:DOT1L inhibitor EPZ-5676 displays synergistic antiproliferative activity in combination with standard of care drugs and hypomethylating agents in MLL-rearranged leukemia cells. Klaus CR, Iwanowicz D, Johnston D, Campbell CA, Smith JJ, Moyer MP, Copeland RA, Olhava EJ, Scott MP, Pollock RM, Daigle SR, Raimondi A.J Pharmacol Exp Ther. 2014 Sep;350(3):646-56. doi: 10.1124/jpet.114.214577. Epub 2014 Jul 3. PMID: 24993360 Free Article</br>7:Nonclinical pharmacokinetics and metabolism of EPZ-5676, a novel DOT1L histone methyltransferase inhibitor. Basavapathruni A, Olhava EJ, Daigle SR, Therkelsen CA, Jin L, Boriack-Sjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP, Dovletoglou A, Richon VM, Pollock RM, Copeland RA, Moyer MP, Chesworth R, Pearson PG, Waters NJ.Biopharm Drug Dispos. 2014 May;35(4):237-52. doi: 10.1002/bdd.1889. Epub 2014 Feb 14. PMID: 24415392

Request a Quote

Contact Us at MuseChem

We are committed to providing you with reliable, cost-effective solutions for your chemical needs, while ensuring your safety and comfort. Our team of experts is always available to answer your questions and help you navigate the complexities of the chemical industry.

Whether you're looking for a specific product or need help with a custom synthesis project, we're here to help you discover a new world of chemical possibilities. Contact us today to learn more about how we can assist you with all of your chemical needs.

Our goal is to make the process of ordering chemicals as seamless and hassle-free as possible. Let us know how we can assist you, and we'll get back to you as soon as possible. We look forward to hearing from you!