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

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

  • ACS Med Chem Lett. 2021 Aug 24;12(10):1539-1545. doi: 10.1021/acsmedchemlett.1c00272.
John W Lampe 1,  Joshua S Alford 1,  P Ann Boriak-Sjodin 1,  Dorothy Brach 1,  Kat Cosmopoulos 1,  Kenneth W Duncan 1,  Sean T Eckley 1,  Megan A Foley 1,  Darren M Harvey 1,  Vinny Motwani 1,  Michael J Munchhof 1,  Alejandra Raimondi 1,  Thomas V Riera 1,  Cuyue Tang 1,  Michael J Thomenius 1,  Jennifer Totman 1,  Neil A Farrow 1
Affiliations

Affiliation

  • 1 Epizyme Inc., 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States.
PMID: 34671445 DOI: 10.1021/acsmedchemlett.1c00272
Abstract

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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z