Genz-644282, identified as a potent topoisomerase I inhibitor, demonstrates significant efficacy across a spectrum of 29 human tumor cell lines with IC50 values ranging from 1.8 nM to 1.8 μM[1]. Genz-644282 exhibits substantial suppressive effects on the PPTP cell lines, with IC50 values between 0.2-21.9 nM and an average IC50 of 1.2 nM[2]. Furthermore, Genz-644282 is effective in stabilizing Top1-DNA covalent cleavage complexes, and at 0.1 μM, it induces γH2AX foci in both human colon cancer HCT116 cells and breast cancer MCF7 cells, demonstrating cytotoxicity in CPT-resistant human cancer cell lines[3].
体内研究
When administered intravenously to mice, Genz-644282 at doses of 1-4 mg/kg induces notable tumor growth delay (TGD) across various human cancer xenograft models, including colon cancer, non-small cell lung carcinoma, and melanoma. Specifically, it achieves a TGD ranging from 14 to 34 days in these models, with the extent of delay varying based on the type of tumor and the dosage administered[1].
At Genz644282's maximum tolerated dose (MTD) of 4 mg/kg, Genz644282 secures maintained complete responses (MCR) in all evaluated solid tumor models (6/6). At a dose of 2 mg/kg, it induces complete responses (CR) or MCR in all tested tumor models (3/3), leading to objective regressions in 41% (7 of 17) of the models, while no objective responses are observed at a dose of 1 mg/kg[2].
体外研究
Genz-644282, identified as a potent topoisomerase I inhibitor, demonstrates significant efficacy across a spectrum of 29 human tumor cell lines with IC50 values ranging from 1.8 nM to 1.8 μM[1].
Genz-644282 exhibits substantial suppressive effects on the PPTP cell lines, with IC50 values between 0.2-21.9 nM and an average IC50 of 1.2 nM[2].
Furthermore, Genz-644282 is effective in stabilizing Top1-DNA covalent cleavage complexes, and at 0.1 μM, it induces γH2AX foci in both human colon cancer HCT116 cells and breast cancer MCF7 cells, demonstrating cytotoxicity in CPT-resistant human cancer cell lines[3].
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