| 产品描述： | Genz-644282, a novel non-camptothecin topoisomerase I inhibitor for cancer treatment |
| 靶点： |
Topoisomerase |
| 体外研究： |
Human bone marrow CFU-GM was more sensitive to the Top1 inhibitors than was mouse bone marrow CFU-GM. The ratio of mouse to human IC(90) values was more than 10 for the camptothecins and less than 10 for Genz-644282, which had more potency as a cytotoxic agent toward human tumor cells in culture than the camptothecins in the colony-forming and 72-hour proliferation assays. Genz-644282 has superior or equal antitumor activity in the human tumor xenografts than the standard drug comparators |
| 体内研究： |
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 |
| 细胞实验： |
Colony-forming assays were conducted with mouse and human bone marrow and eight human tumor cell lines. In addition, 29 human tumor cell lines representing a range of histology and potential resistance mechanisms were assayed for sensitivity to Genz-644282 in a 72-hour exposure assay. The efficacy of Genz-644282 was compared with standard anticancer drugs (i.e., irinotecan, docetaxel, and dacarbazine) in human tumor xenografts of colon cancer, renal cell carcinoma, non-small cell lung cancer, and melanoma. |
| 动物实验： |
Genz-644282 was tested against the PPTP in vitro panel (0.1 nM to 1 μM), and in vivo using three times per week × 2 schedule repeated at day 21 at its maximum tolerated dose (MTD) of 4 mg/kg. Subsequently Genz-644282 was tested at 4, 3, 2, and 1 mg/kg in 3 models to assess the dose-response relationship. mRNA gene signatures predictive for Genz-644282 response in vitro were applied to select 15 tumor models that were evaluated prospectively. |
| 参考文献： |
1. Kurtzberg L S , Roth S , Krumbholz R , et al. Genz-644282, a Novel Non-Camptothecin Topoisomerase I Inhibitor for Cancer Treatment[J]. Clinical Cancer Research, 2011, 17(9):2777-2787. 2. Houghton P J , Lock R , Carol H , et al. Testing of the Topoisomerase 1 Inhibitor Genz644282 by the Pediatric Preclinical Testing Program[J]. Pediatric Blood & Cancer, 2012, 58(2):200-209. |
| 溶解性： |
Soluble in DMSO |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.454 ml |
12.272 ml |
24.545 ml |
| 5 mM |
0.491 ml |
2.454 ml |
4.909 ml |
| 10 mM |
0.245 ml |
1.227 ml |
2.454 ml |
| 50 mM |
0.049 ml |
0.245 ml |
0.491 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京