9UZT

Crystal structure of human PTPN2 with inhibitor K-38

これはPDB形式変換不可エントリーです。

9UZT の概要

• エントリーDOI: 10.2210/pdb9uzt/pdb
• 分子名称: Tyrosine-protein phosphatase non-receptor type 2, ~{N}-cycloheptyl-4-[3-fluoranyl-5-oxidanyl-4-[1,1,4-tris(oxidanylidene)-1,2,5-thiadiazolidin-2-yl]phenyl]-1~{H}-imidazole-2-carboxamide (3 entities in total)
• 機能のキーワード: ptpn2, inhibitor, tumor immunity, immune system
• 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: 35384.05

構造登録者

Tong, C. (登録日: 2025-05-16, 公開日: 2025-12-17)

主引用文献

Kuang, W.,Li, Q.,Wang, W.,Wang, D.,Tong, C.,Song, M.,Han, K.,Liu, J.,Chen, A.,Chen, Y.,Wang, L.,Hao, H.,Wang, X.,Xiao, Y.,Yang, P.
Targeting Protein Tyrosine Phosphatase Nonreceptor Type 2 with a Novel Inhibitor for the Treatment of Melanoma.
J.Med.Chem., 68:24649-24671, 2025

PubMed Abstract: Melanoma is a highly aggressive skin cancer with strong metastatic potential, posing significant clinical challenges. Currently, melanoma treatment commonly includes chemotherapy and immunotherapy; nevertheless, the treatment modalities have specific limitations. PTPN2 (protein tyrosine phosphatase nonreceptor type 2) has emerged as a promising therapeutic target. Through rational drug design, we identified compound , a potent PTPN2 inhibitor (IC = 7.05 nM) with high safety (hERG IC > 40 μM) and excellent liver metabolic stability ( = 408 min). Compound also showed improved oral bioavailability ( = 10.46%) over ( = 1.40%) (Zheng 2024, 270, 116390, ). In vivo, compound significantly suppressed melanoma growth, especially when combined with anti-PD-1 therapy, outperforming . It enhanced lymphocyte infiltration into tumors and modulated IFN-γ signaling pathways. These findings indicate that compound is a potent small molecule inhibitor of PTPN2, laying the groundwork for the future development of PTPN2-targeted therapeutics.

PubMed: 41204903
DOI: 10.1021/acs.jmedchem.5c02622

実験手法

X-RAY DIFFRACTION (2.17 Å)