5CCM

Crystal structure of SMYD3 with SAM and EPZ030456

Summary for 5CCM

• Entry DOI: 10.2210/pdb5ccm/pdb
• Related: 5CCL
• Descriptor: Histone-lysine N-methyltransferase SMYD3, ZINC ION, S-ADENOSYLMETHIONINE, ... (5 entities in total)
• Functional Keywords: protein-inhibitor complex, methyltransferase, epigenetics, drug discovery, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q9H7B4
• Total number of polymer chains: 1
• Total formula weight: 50316.89

Authors

Boriack-Sjodin, P.A. (deposition date: 2015-07-02, release date: 2015-09-09, Last modification date: 2024-03-06)

Primary citation

Mitchell, L.H.,Boriack-Sjodin, P.A.,Smith, S.,Thomenius, M.,Rioux, N.,Munchhof, M.,Mills, J.E.,Klaus, C.,Totman, J.,Riera, T.V.,Raimondi, A.,Jacques, S.L.,West, K.,Foley, M.,Waters, N.J.,Kuntz, K.W.,Wigle, T.J.,Scott, M.P.,Copeland, R.A.,Smith, J.J.,Chesworth, R.
Novel Oxindole Sulfonamides and Sulfamides: EPZ031686, the First Orally Bioavailable Small Molecule SMYD3 Inhibitor.
Acs Med.Chem.Lett., 7:134-138, 2016

PubMed 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.

PubMed: 26985287
DOI: 10.1021/acsmedchemlett.5b00272

Experimental method

X-RAY DIFFRACTION (2.3 Å)