| Autor: |
Thomas V. Riera, Lampe John W, Cuyue Tang, Kat Cosmopoulos, Alejandra Raimondi, Michael John Munchhof, Neil A. Farrow, Kenneth W. Duncan, Dorothy Brach, Vinny Motwani, Darren Martin Harvey, P. Ann Boriak-Sjodin, Sean T. Eckley, Jennifer Totman, Joshua S Alford, Megan Alene Cloonan Foley, Michael J Thomenius |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
ACS Medicinal Chemistry Letters |
| ISSN: |
1948-5875 |
| Popis: |
SET domain-containing protein 2 (SETD2), a histone methyltransferase, has been identified as a target of interest in certain hematological malignancies, including multiple myeloma. This account details the discovery of EPZ-719, a novel and potent SETD2 inhibitor with a high selectivity over other histone methyltransferases. A screening campaign of the Epizyme proprietary histone methyltransferase-biased library identified potential leads based on a 2-amidoindole core. Structure-based drug design (SBDD) and drug metabolism/pharmacokinetics (DMPK) optimization resulted in EPZ-719, an attractive tool compound for the interrogation of SETD2 biology that enables in vivo target validation studies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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