2X9E

HUMAN MPS1 IN COMPLEX WITH NMS-P715

2X9E の概要

• エントリーDOI: 10.2210/pdb2x9e/pdb
• 関連するPDBエントリー: 2ZMC 2ZMD 3CEK 3DBQ 3GFW 3H9F 3HMN 3HMO 3HMP
• 分子名称: DUAL SPECIFICITY PROTEIN KINASE TTK, N-(2,6-DIETHYLPHENYL)-1-METHYL-8-({4-[(1-METHYLPIPERIDIN-4-YL)CARBAMOYL]-2-(TRIFLUOROMETHOXY)PHENYL}AMINO)-4,5-DIHYDRO-1H-PYRAZOLO[4,3-H]QUINAZOLINE-3-CARBOXAMIDE (3 entities in total)
• 機能のキーワード: kinase, serine/threonine-protein kinase, transferase, tyrosine-protein kinase, mitotic checkpoint
• 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: 36916.38

構造登録者

Colombo, R.,Caldarelli, M.,Mennecozzi, M.,Giorgini, M.L.,Sola, F.,Cappella, P.,Perrera, C.,DePaolini, S.R.,Rusconi, L.,Cucchi, U.,Avanzi, N.,Bertrand, J.A.,Bossi, R.T.,Pesenti, E.,Galvani, A.,Isacchi, A.,Colotta, F.,Donati, D.,Moll, J. (登録日: 2010-03-17, 公開日: 2010-12-29, 最終更新日: 2023-12-20)

主引用文献

Colombo, R.,Caldarelli, M.,Mennecozzi, M.,Giorgini, M.L.,Sola, F.,Cappella, P.,Perrera, C.,Depaolini, S.R.,Rusconi, L.,Cucchi, U.,Avanzi, N.,Bertrand, J.A.,Bossi, R.T.,Pesenti, E.,Galvani, A.,Isacchi, A.,Colotta, F.,Donati, D.,Moll, J.
Targeting the Mitotic Checkpoint for Cancer Therapy with Nms-P715, an Inhibitor of Mps1 Kinase.
Cancer Res., 70:10255-, 2010

PubMed Abstract: MPS1 kinase is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. It has been found aberrantly overexpressed in a wide range of human tumors and is necessary for tumoral cell proliferation. Here we report the identification and characterization of NMS-P715, a selective and orally bioavailable MPS1 small-molecule inhibitor, which selectively reduces cancer cell proliferation, leaving normal cells almost unaffected. NMS-P715 accelerates mitosis and affects kinetochore components localization causing massive aneuploidy and cell death in a variety of tumoral cell lines and inhibits tumor growth in preclinical cancer models. Inhibiting the SAC could represent a promising new approach to selectively target cancer cells.

PubMed: 21159646
DOI: 10.1158/0008-5472.CAN-10-2101

実験手法

X-RAY DIFFRACTION (3.1 Å)