7FAI

CARM1 bound with compound 9

Summary for 7FAI

• Entry DOI: 10.2210/pdb7fai/pdb
• Descriptor: Histone-arginine methyltransferase CARM1, N'-[[3-[4-(3,5-dimethyl-1,2-oxazol-4-yl)-5-methyl-6-(oxan-4-ylamino)pyrimidin-2-yl]phenyl]methyl]-N-methyl-ethane-1,2-diamine (3 entities in total)
• Functional Keywords: histone-arginine methyltransferase carm1, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 154716.70

Authors

Cao, D.Y.,Li, J.,Xiong, B. (deposition date: 2021-07-06, release date: 2021-11-24, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.09749259173 Å)