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Lurbinectedin

CAS No. : 497871-47-3

產品活性：Lurbinectedin (PM01183) is a DNA minor groove covalent binder with potent anti-tumour activity; inhibits RMG1 and RMG2 cell growth with IC₅₀ values of 1.25 and 1.16 nM, respectively.

研究領域：Cell Cycle/DNA Damage

作用靶點：DNA Alkylator/Crosslinker  |  DNA/RNA Synthesis

In Vitro: PM01183 is a new synthetic tetrahydroisoquinoline alkaloid that is currently in phase I clinical development for the treatment of solid tumours. PM01183–DNA adducts in living cells give rise to double-strand breaks, triggering S-phase accumulation and apoptosis. The potent cytotoxic activity of PM01183 is ascertained in a 23-cell line panel with a mean GI₅₀ value of 2.7 nM. Lurbinectedin exhibits significant antitumor activity toward chemosensitive and chemoresistant human ovarian clear cell carcinoma (CCC) cells in vitro.

In Vivo: Mouse CCC cell xenografts reveals that lurbinectedin significantly inhibits tumor growth. Lurbinectedin plus SN-38 results in a significant synergistic effect. In four murine xenograft models of human cancer, PM01183 inhibits tumour growth significantly with no weight loss of treated animals. Single lurbinectedin or NSC 119875-combined therapies are effective in treating NSC 119875-sensitive and NSC 119875-resistant preclinical ovarian tumor models. The strongest synergistic effect is observed for combined treatments, especially in NSC 119875-resistant tumors. Lurbinectedin tumor growth inhibition is associated with reduced proliferation, increased rate of aberrant mitosis, and subsequent induced apoptosis.

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