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Genz-644282 is a cytotoxic agent and shows activity in several human tumor cell lines. In vitro, Genz-644282 demonstrated potent cytotoxic activity with a median IC(50) of 1.2 nM (range 0.2-21.9 nM). In vivo, Genz-644282 at its MTD (4 mg/kg) induced maintained complete responses (MCR) in 6/6 evaluable solid tumor models. At 2 mg/kg Genz-644282 induced CR or MCR in 3/3 tumor models relatively insensitive to topotecan, but there were no objective responses at 1 mg/kg. Further testing at 2 mg/kg showed that Genz-644282 induced objective regressions in 7 of 17 (41%) models. There was a significant correlation between predictive response scores based on Affymetrix U133Plus2 baseline tumor expression profiles and the observed in vivo responses to Genz-644282. Genz-644282 was highly active within a narrow dose range (2-4 mg/kg), typical of other topoisomerase I poisons. Genz-644282 has superior or equal antitumor activity in the human tumor xenografts than the standard compound comparators.
| Molecular Weight | 407.42 |
| Formula | C22H21N3O5 |
| CAS Number | 529488-28-6 |
| Solubility (25°C) | DMSO 10 mM |
| Storage | 2-8°C, protect from light |
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