7FAJ

CARM1 bound with compound 43

7FAJ の概要

• エントリーDOI: 10.2210/pdb7faj/pdb
• 分子名称: Histone-arginine methyltransferase CARM1, N'-[[3-[4-(3,5-dimethyl-1,2-oxazol-4-yl)-5-methyl-6-phenylazanyl-pyrimidin-2-yl]phenyl]methyl]-N-methyl-ethane-1,2-diamine (3 entities in total)
• 機能のキーワード: histone-arginine methyltransferase carm1, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 154684.62

構造登録者

Cao, D.Y.,Li, J.,Xiong, B. (登録日: 2021-07-06, 公開日: 2021-11-24, 最終更新日: 2023-11-29)

主引用文献

Zhang, Z.,Guo, Z.,Xu, X.,Cao, D.,Yang, H.,Li, Y.,Shi, Q.,Du, Z.,Guo, X.,Wang, X.,Chen, D.,Zhang, Y.,Chen, L.,Zhou, K.,Li, J.,Geng, M.,Huang, X.,Xiong, B.
Structure-Based Discovery of Potent CARM1 Inhibitors for Solid Tumor and Cancer Immunology Therapy.
J.Med.Chem., 64:16650-16674, 2021

PubMed Abstract: CARM1 is a protein arginine methyltransferase and acts as a transcriptional coactivator regulating multiple biological processes. Aberrant expression of CARM1 has been related to the progression of multiple types of cancers, and therefore CARM1 was considered as a promising drug target. In the present work, we report the structure-based discovery of a series of -(3-(pyrimidin-2-yl)benzyl)ethane-1,2-diamines as potent CARM1 inhibitors, in which compound displays high potency and selectivity. With the advantage of excellent tissue distribution, compound demonstrated good in vivo efficacy for solid tumors. Furthermore, from the detailed immuno-oncology study with MC38 C57BL/6J xenograft model, we confirmed that this chemical probe has profound effects in tumor immunity, which paves the way for future studies on the modulation of arginine post-translational modification that could be utilized in solid tumor treatment and cancer immunotherapy.

PubMed: 34781683
DOI: 10.1021/acs.jmedchem.1c01308

実験手法

X-RAY DIFFRACTION (2.24507255823 Å)