2. Academic Validation
  3. Novel Oxindole Sulfonamides and Sulfamides: EPZ031686, the First Orally Bioavailable Small Molecule SMYD3 Inhibitor

Novel Oxindole Sulfonamides and Sulfamides: EPZ031686, the First Orally Bioavailable Small Molecule SMYD3 Inhibitor

  • ACS Med Chem Lett. 2015 Aug 27;7(2):134-8. doi: 10.1021/acsmedchemlett.5b00272.
Lorna H Mitchell 1,  P Ann Boriack-Sjodin 1,  Sherri Smith 1,  Michael Thomenius 1,  Nathalie Rioux 1,  Michael Munchhof 1,  James E Mills 1,  Christine Klaus 1,  Jennifer Totman 1,  Thomas V Riera 1,  Alejandra Raimondi 1,  Suzanne L Jacques 1,  Kip West 1,  Megan Foley 1,  Nigel J Waters 1,  Kevin W Kuntz 1,  Tim J Wigle 1,  Margaret Porter Scott 1,  Robert A Copeland 1,  Jesse J Smith 1,  Richard Chesworth 1
Affiliations

Affiliation

  • 1 Epizyme Inc. , Fourth Floor, 400 Technology Square, Cambridge, Massachusetts 02139, United States.
PMID: 26985287 DOI: 10.1021/acsmedchemlett.5b00272
Abstract

SMYD3 has been implicated in a range of cancers; however, until now no potent selective small molecule inhibitors have been available for target validation studies. A novel oxindole series of SMYD3 inhibitors was identified through screening of the Epizyme proprietary histone methyltransferase-biased library. Potency optimization afforded two tool compounds, sulfonamide EPZ031686 and sulfamide EPZ030456, with cellular potency at a level sufficient to probe the in vitro biology of SMYD3 inhibition. EPZ031686 shows good bioavailability following oral dosing in mice making it a suitable tool for potential in vivo target validation studies.

Keywords

KMT; SMYD3; methyltransferase; oncology; oxindole; tool compound.

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