7LZB

Crystal Structure of SETD2 bound to Compound 2

7LZB の概要

• エントリーDOI: 10.2210/pdb7lzb/pdb
• 分子名称: Histone-lysine N-methyltransferase SETD2, ZINC ION, S-ADENOSYLMETHIONINE, ... (6 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32970.72

構造登録者

Farrow, N.A.,Boriack-Sjodin, P. (登録日: 2021-03-09, 公開日: 2021-09-22, 最終更新日: 2023-10-18)

主引用文献

Lampe, J.W.,Alford, J.S.,Boriak-Sjodin, P.A.,Brach, D.,Cosmopoulos, K.,Duncan, K.W.,Eckley, S.T.,Foley, M.A.,Harvey, D.M.,Motwani, V.,Munchhof, M.J.,Raimondi, A.,Riera, T.V.,Tang, C.,Thomenius, M.J.,Totman, J.,Farrow, N.A.
Discovery of a First-in-Class Inhibitor of the Histone Methyltransferase SETD2 Suitable for Preclinical Studies.
Acs Med.Chem.Lett., 12:1539-1545, 2021

PubMed 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 , 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 , an attractive tool compound for the interrogation of SETD2 biology that enables target validation studies.

PubMed: 34671445
DOI: 10.1021/acsmedchemlett.1c00272

実験手法

X-RAY DIFFRACTION (2.28 Å)