534605-78-2

TP-300, also known as CH-0793076; TP-3076, is a DNA topoisomerase I inhibitor potentially for the treatment of colorectal cancer, gastric cancer. TP300 is stable in an acidic solution but is rapidly converted to CH0793076 under physiological pH conditions such as in sera. This efficient prodrug activation would minimize interpatient differences in pharmacokinetic and toxicity profiles. Unlike CPT-11, TP300 does not exhibit cholinergic interaction or cause acute diarrhea at effective doses. In mouse xenograft models, TP300 showed antitumor activity against both BCRP-positive and -negative xenografts, whereas CPT-11 was less active against BCRP-positive xenografts.

CH-0793076 (TP3076)，喜树碱的六环类似物，是 TP300 的活性药物和主要代谢物。CH-0793076 抑制 DNA 拓扑异构酶I (DNA topoisomerase I)，IC50 为 2.3 μM。CH-0793076 对表达 BCRP (乳腺癌耐药蛋白) 的细胞也有活性。