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• W4313361981 abstract "Colorectal cancer is one of the most common malignancies, and the topoisomerase inhibitor irinotecan (CPT-11)-based chemotherapeutic regimen is currently the first-line treatment with impressive therapeutic efficacy. However, irinotecan has several clinically significant side effects, including diarrhea, which limit its clinical utility and efficacy in many patients. In an effort to discover better and improved pharmacotherapy against colorectal cancer, we synthesized a novel topoisomerase inhibitor, PCC0208037, examined its anti-tumor efficacy and related molecular mechanisms, and characterized its toxicity and pharmacokinetic profiles. PCC0208037 suppressed colorectal cancer cell (CRC) proliferation and increased cell cycle arrest, which may be related to its effects on up-regulating DNA damage response (DDR)-related molecules and apoptosis-related proteins. PCC0208037 demonstrated robust anti-tumor activity in vivo in a colorectal cancer cell xenograft model, which was comparable to or slightly better than CPT-11. In a preliminary toxicology study, PCC0208037 demonstrated much weaker tissue damage to colorectal tissue than CPT-11, and its impacts on food intake and body weight loss were more transient and recovered faster than CPT-11 in mice. This could be partially explained by the pharmacokinetic findings, which showed that PCC0208037 and its active metabolite, SN-38, were more accumulated in tumor tissue than in the intestine, as compared to CPT-11. Taken together, these results described a novel Topo I inhibitor with a comparative advantage over the standard treatment of colorectal cancer CPT-11 and could be a promising candidate compound for the treatment of colorectal cancer that warrants further investigation." @default.
• W4313361981 created "2023-01-06" @default.
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• W4313361981 date "2022-12-30" @default.
• W4313361981 modified "2023-09-27" @default.
• W4313361981 title "Anti-Colorectal Cancer Effects of a Novel Camptothecin Derivative PCC0208037 In Vitro and In Vivo" @default.
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• W4313361981 doi "https://doi.org/10.3390/ph16010053" @default.
• W4313361981 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36678550" @default.
• W4313361981 hasPublicationYear "2022" @default.
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