Tazemetostat
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MedKoo CAT#: 406265

CAS#: 1403254-99-8

Description: Tazemetostat, also known as EPZ-6438 and E7438, is a potent, selective, and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity. EPZ-6438 induces apoptosis and differentiation specifically in SMARCB1-deleted MRT cells. Treatment of xenograft-bearing mice with EPZ-6438 leads to dose-dependent regression of MRTs with correlative diminution of intratumoral trimethylation levels of lysine 27 on histone H3, and prevention of tumor regrowth after dosing cessation. These data demonstrate the dependency of SMARCB1 mutant MRTs on EZH2 enzymatic activity and portend the utility of EZH2-targeted drugs for the treatment of these genetically defined cancers.


Chemical Structure

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Tazemetostat
CAS# 1403254-99-8

Theoretical Analysis

MedKoo Cat#: 406265
Name: Tazemetostat
CAS#: 1403254-99-8
Chemical Formula: C34H44N4O4
Exact Mass: 572.33626
Molecular Weight: 572.74
Elemental Analysis: C, 71.30; H, 7.74; N, 9.78; O, 11.17

Price and Availability

Size Price Availability Quantity
50.0mg USD 90.0 Same day
100.0mg USD 150.0 Same day
200.0mg USD 250.0 Same day
500.0mg USD 550.0 Same day
1.0g USD 950.0 Same day
2.0g USD 1710.0 Same day
5.0g USD 3850.0 Same day
10.0g USD 6950.0 Same day
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Synonym: EPZ-6438; EPZ 6438; EPZ6438; E7438; E-7438; E 7438; Tazemetostat

IUPAC/Chemical Name: N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide

InChi Key: NSQSAUGJQHDYNO-UHFFFAOYSA-N

InChi Code: InChI=1S/C34H44N4O4/c1-5-38(29-10-14-41-15-11-29)32-20-28(27-8-6-26(7-9-27)22-37-12-16-42-17-13-37)19-30(25(32)4)33(39)35-21-31-23(2)18-24(3)36-34(31)40/h6-9,18-20,29H,5,10-17,21-22H2,1-4H3,(H,35,39)(H,36,40)

SMILES Code: O=C(C1=CC(C2=CC=C(CN3CCOCC3)C=C2)=CC(N(CC)C4CCOCC4)=C1C)NCC5=C(C)C=C(C)NC5=O

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 572.74 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: Knutson SK, Kawano S, Minoshima Y, Warholic NM, Huang KC, Xiao Y, Kadowaki T, Uesugi M, Kuznetsov G, Kumar N, Wigle TJ, Klaus CR, Allain CJ, Raimondi A, Waters NJ, Smith JJ, Porter-Scott M, Chesworth R, Moyer MP, Copeland RA, Richon VM, Uenaka T, Pollock RM, Kuntz KW, Yokoi A, Keilhack H. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mol Cancer Ther. 2014 Apr;13(4):842-54. doi: 10.1158/1535-7163.MCT-13-0773. PubMed PMID: 24563539.

2: Kurmasheva RT, Sammons M, Favours E, Wu J, Kurmashev D, Cosmopoulos K, Keilhack H, Klaus CR, Houghton PJ, Smith MA. Initial testing (stage 1) of tazemetostat (EPZ-6438), a novel EZH2 inhibitor, by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2017 Mar;64(3). doi: 10.1002/pbc.26218. PubMed PMID: 27555605.

3: Wiese M, Schill F, Sturm D, Pfister S, Hulleman E, Johnsen SA, Kramm CM. No Significant Cytotoxic Effect of the EZH2 Inhibitor Tazemetostat (EPZ-6438) on Pediatric Glioma Cells with Wildtype Histone 3 or Mutated Histone 3.3. Klin Padiatr. 2016 Apr;228(3):113-7. doi: 10.1055/s-0042-105292. PubMed PMID: 27135271.

4: Baker T, Nerle S, Pritchard J, Zhao B, Rivera VM, Garner A, Gonzalvez F. Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitors. Oncotarget. 2015 Oct 20;6(32):32646-55. doi: 10.18632/oncotarget.5066. PubMed PMID: 26360609; PubMed Central PMCID: PMC4741719.

5: Zhang P, de Gooijer MC, Buil LC, Beijnen JH, Li G, van Tellingen O. ABCB1 and ABCG2 restrict the brain penetration of a panel of novel EZH2-Inhibitors. Int J Cancer. 2015 Oct 15;137(8):2007-18. doi: 10.1002/ijc.29566. PubMed PMID: 25868794.

6: Xia B, Gerstin E, Schones DE, Huang W, Steven de Belle J. Transgenerational programming of longevity through E(z)-mediated histone H3K27 trimethylation in Drosophila. Aging (Albany NY). 2016 Nov 25;8(11):2988-3008. doi: 10.18632/aging.101107. PubMed PMID: 27889707; PubMed Central PMCID: PMC5191882.

7: Knutson SK, Warholic NM, Johnston LD, Klaus CR, Wigle TJ, Iwanowicz D, Littlefield BA, Porter-Scott M, Smith JJ, Moyer MP, Copeland RA, Pollock RM, Kuntz KW, Raimondi A, Keilhack H. Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas. PLoS One. 2014 Dec 10;9(12):e111840. doi: 10.1371/journal.pone.0111840. PubMed PMID: 25493630; PubMed Central PMCID: PMC4262195.

8: Adhikary G, Grun D, Balasubramanian S, Kerr C, Huang JM, Eckert RL. Survival of skin cancer stem cells requires the Ezh2 polycomb group protein. Carcinogenesis. 2015 Jul;36(7):800-10. doi: 10.1093/carcin/bgv064. PubMed PMID: 25969142; PubMed Central PMCID: PMC4580538.

9: Momparler RL, Côté S. Targeting of cancer stem cells by inhibitors of DNA and histone methylation. Expert Opin Investig Drugs. 2015;24(8):1031-43. doi: 10.1517/13543784.2015.1051220. Review. PubMed PMID: 26004134.

10: Edfeldt K, Hellman P, Westin G, Stalberg P. A plausible role for actin gamma smooth muscle 2 (ACTG2) in small intestinal neuroendocrine tumorigenesis. BMC Endocr Disord. 2016 Apr 23;16:19. doi: 10.1186/s12902-016-0100-3. PubMed PMID: 27107594; PubMed Central PMCID: PMC4841950.

11: Kim KH, Roberts CW. Targeting EZH2 in cancer. Nat Med. 2016 Feb;22(2):128-34. doi: 10.1038/nm.4036. Review. PubMed PMID: 26845405; PubMed Central PMCID: PMC4918227.

12: Huang Y, Zhang J, Yu Z, Zhang H, Wang Y, Lingel A, Qi W, Gu XJ, Zhao K, Shultz MD, Wang L, Fu X, Sun Y, Zhang Q, Jiang X, Zhang JW, Zhang C, Li L, Zeng J, Feng L, Zhang C, Liu Y, Zhang M, Zhang L, Zhao M, Gao Z, Liu X, Fang D, Guo H, Mi Y, Gabriel T, Dillon MP, Atadja P, Oyang C. Discovery of First-in-Class, Potent and Orally Bioavailable EED inhibitor with Robust Anti-cancer Efficacy. J Med Chem. 2017 Jan 16. doi: 10.1021/acs.jmedchem.6b01576. [Epub ahead of print] PubMed PMID: 28092155.

13: Fisher ML, Adhikary G, Grun D, Kaetzel DM, Eckert RL. The Ezh2 polycomb group protein drives an aggressive phenotype in melanoma cancer stem cells and is a target of diet derived sulforaphane. Mol Carcinog. 2016 Dec;55(12):2024-2036. doi: 10.1002/mc.22448. PubMed PMID: 26693692; PubMed Central PMCID: PMC4919248.

14: Chen JF, Luo X, Xiang LS, Li HT, Zha L, Li N, He JM, Xie GF, Xie X, Liang HJ. EZH2 promotes colorectal cancer stem-like cell expansion by activating p21cip1-Wnt/β-catenin signaling. Oncotarget. 2016 Jul 5;7(27):41540-41558. doi: 10.18632/oncotarget.9236. PubMed PMID: 27172794; PubMed Central PMCID: PMC5173077.

15: Yan W, Herman JG, Guo M. Epigenome-based personalized medicine in human cancer. Epigenomics. 2016 Jan;8(1):119-33. doi: 10.2217/epi.15.84. Review. PubMed PMID: 26344672.



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