7L1X

Structure of human CK2 alpha kinase (catalytic subunit) with the inhibitor 108600.

7L1X の概要

• エントリーDOI: 10.2210/pdb7l1x/pdb
• 分子名称: Casein kinase II subunit alpha, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: inhibitor 108600, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 40949.28

構造登録者

Rechkoblit, O.,Aggarwal, A.K. (登録日: 2020-12-15, 公開日: 2021-08-11, 最終更新日: 2026-04-15)

主引用文献

Sato, K.,Padgaonkar, A.A.,Baker, S.J.,Cosenza, S.C.,Rechkoblit, O.,Subbaiah, D.R.C.V.,Domingo-Domenech, J.,Bartkowski, A.,Port, E.R.,Aggarwal, A.K.,Ramana Reddy, M.V.,Irie, H.Y.,Premkumar Reddy, E.
Simultaneous CK2/TNIK/DYRK1 inhibition by 108600 suppresses triple negative breast cancer stem cells and chemotherapy-resistant disease.
Nat Commun, 12:4671-4671, 2021

PubMed Abstract: Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSCs) have been proposed to represent a chemotherapy-resistant subpopulation responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. Here, we describe a novel multi-kinase inhibitor, 108600, that targets the TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of BCSCs and induces G2M arrest and apoptosis of TNBC cells. In vivo, 108600 treatment of mice bearing triple negative tumors results in the induction of apoptosis and overcomes chemotherapy resistance. Finally, treatment with 108600 and chemotherapy suppresses growth of pre-established TNBC metastases, providing additional support for the clinical translation of this agent to clinical trials.

PubMed: 34344863
DOI: 10.1038/s41467-021-24878-z

実験手法

X-RAY DIFFRACTION (1.8 Å)