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• W3043668595 abstract "Mismatch repair (MMR) deficiencies are a hallmark of various cancers causing accumulation of DNA mutations and mismatches, which often results in chemotherapy resistance. Metalloinsertor complexes, including [Rh(chrysi)(phen)(PPO)]Cl2 (Rh-PPO), specifically target DNA mismatches and selectively induce cytotoxicity within MMR-deficient cells. Here, we present an in vivo analysis of Rh-PPO, our most potent metalloinsertor. Studies with HCT116 xenograft tumors revealed a 25% reduction in tumor volume and 12% increase in survival with metalloinsertor treatment (1 mg/kg; nine intraperitoneal doses over 20 d). When compared to oxaliplatin, Rh-PPO displays ninefold higher potency at tumor sites. Pharmacokinetic studies revealed rapid absorption of Rh-PPO in plasma with notable accumulation in the liver compared to tumors. Additionally, intratumoral metalloinsertor administration resulted in enhanced anticancer effects, pointing to a need for more selective delivery methods. Overall, these data show that Rh-PPO inhibits xenograft tumor growth, supporting the strategy of using Rh-PPO as a chemotherapeutic targeted to MMR-deficient cancers." @default.
• W3043668595 created "2020-07-23" @default.
• W3043668595 creator A5010855228 @default.
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• W3043668595 date "2020-07-13" @default.
• W3043668595 modified "2023-10-18" @default.
• W3043668595 title "In vivo anticancer activity of a rhodium metalloinsertor in the HCT116 xenograft tumor model" @default.
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• W3043668595 doi "https://doi.org/10.1073/pnas.2006569117" @default.
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• W3043668595 hasPublicationYear "2020" @default.
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