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Clinically relevant GSK?3? inhibitor 9?ING?41 is active as a single agent and in combination with other antitumor therapies in human renal cancer.

ABSTRACT: Glycogen synthase kinase?3 (GSK?3), a serine/threonine kinase, is involved in a broad range of pathological processes including cancer. GSK?3 has two isoforms, GSK?3? and GSK?3?, and GSK?3? has been recognized as a therapeutic target for the development of new anticancer drugs. The present study aimed to investigate the antitumor effects of 9?ING?41, which is a maleimide?based ATP?competitive small molecule GSK?3? inhibitor active in patients with advanced cancer. In renal cancer cell lines, treatment with 9?ING?41 alone induced cell cycle arrest and apoptosis, and autophagy inhibitors increased the antitumor effects of 9?ING?41 when used in combination. Treatment with 9?ING?41 potentiated the antitumor effects of targeted therapeutics and increased the cytotoxic effects of cytokine?activated immune cells on renal cancer cell lines. These results provided a compelling rationale for the inclusion of patients with renal cancer in studies of 9?ING?41, both as a single agent and in combination with current standard therapies.

SUBMITTER: Anraku T 

PROVIDER: S-EPMC6984786 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer.

Anraku Tsutomu T   Kuroki Hiroo H   Kazama Akira A   Bilim Vladimir V   Tasaki Masaaki M   Schmitt Daniel D   Mazar Andrew A   Giles Francis J FJ   Ugolkov Andrey A   Tomita Yoshihiko Y  

International journal of molecular medicine 20191212 2

Glycogen synthase kinase‑3 (GSK‑3), a serine/threonine kinase, is involved in a broad range of pathological processes including cancer. GSK‑3 has two isoforms, GSK‑3α and GSK‑3β, and GSK‑3β has been recognized as a therapeutic target for the development of new anticancer drugs. The present study aimed to investigate the antitumor effects of 9‑ING‑41, which is a maleimide‑based ATP‑competitive small molecule GSK‑3β inhibitor active in patients with advanced cancer. In renal cancer cell lines, tre  ...[more]

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