KW-2189

KW-2189 is a semi-synthetic, water-soluble analog of duocarmycin B2, a potent antitumor antibiotic produced by *Streptomyces* species. It belongs to the cyclopropylpyrroloindole (CPI) class of DNA alkylating agents. KW-2189 acts as a prodrug that is converted by carboxyl esterase into its active form, DU-86. The active metabolite binds to the minor groove of DNA and induces DNA alkylation and strand breaks, leading to cell cycle arrest and apoptosis. Developed by Kyowa Hakko Kogyo, KW-2189 was evaluated in Phase I and Phase II clinical trials for various solid tumors, including metastatic renal cell carcinoma, small cell lung cancer, and melanoma. However, clinical development was largely discontinued due to limited efficacy and significant hematological toxicities, such as delayed neutropenia and thrombocytopenia.

Other names

duocarmycin B2 analogminactivin