دورية أكاديمية
أعرض في EDS

Discovery of a First-in-Class Inhibitor of the Histone Methyltransferase SETD2 Suitable for Preclinical Studies.

التفاصيل البيبلوغرافية
العنوان: Discovery of a First-in-Class Inhibitor of the Histone Methyltransferase SETD2 Suitable for Preclinical Studies.
المؤلفون: Lampe JW; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Alford JS; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Boriak-Sjodin PA; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Brach D; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Cosmopoulos K; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Duncan KW; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Eckley ST; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Foley MA; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Harvey DM; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Motwani V; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Munchhof MJ; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Raimondi A; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Riera TV; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Tang C; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Thomenius MJ; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Totman J; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States., Farrow NA; Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States.
المصدر: ACS medicinal chemistry letters [ACS Med Chem Lett] 2021 Aug 24; Vol. 12 (10), pp. 1539-1545. Date of Electronic Publication: 2021 Aug 24 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101521073 Publication Model: eCollection Cited Medium: Print ISSN: 1948-5875 (Print) Linking ISSN: 19485875 NLM ISO Abbreviation: ACS Med Chem Lett Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society
مستخلص: 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.
Competing Interests: The authors declare the following competing financial interest(s): All authors are/were employees of Epizyme, Inc. Work was funded by Epizyme.
(© 2021 The Authors. Published by American Chemical Society.)
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تواريخ الأحداث: Date Created: 20211021 Latest Revision: 20211022
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8521618
DOI: 10.1021/acsmedchemlett.1c00272
PMID: 34671445
قاعدة البيانات: MEDLINE
الوصف
تدمد:1948-5875
DOI:10.1021/acsmedchemlett.1c00272