The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo

新型 JNK 抑制剂 AS602801 在体内和体外抑制癌症干细胞

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作者:Masashi Okada, Kenta Kuramoto, Hiroyuki Takeda, Hikaru Watarai, Hirotsugu Sakaki, Shizuka Seino, Manabu Seino, Shuhei Suzuki, Chifumi Kitanaka

Abstract

A phase 2 clinical trial investigating the efficacy and safety of AS602801, a newly developed JNK inhibitor, in the treatment of inflammatory endometriosis is complete. We are now examining whether AS602801 acts against human cancer cells in vitro and in vivo. In vitro, AS602801 exhibited cytotoxicity against both serum-cultured non-stem cancer cells and cancer stem cells derived from human pancreatic cancer, non-small cell lung cancer, ovarian cancer and glioblastoma at concentrations that did not decrease the viability of normal human fibroblasts. AS602801 also inhibited the self-renewal and tumor-initiating capacity of cancer stem cells surviving AS602801 treatment. Cancer stem cells in established xenograft tumors were reduced by systemic administration of AS602801 at a dose and schedule that did not adversely affect the health of the tumor-bearing mice. These findings suggest AS602801 is a promising anti-cancer stem cell agent, and further investigation of the utility of AS602801 in the treatment of cancer seems warranted.

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