Genz-644282 是一种非喜树碱类拓扑异构酶 I (t

Genz-644282  

Genz-644282 是一种非喜树碱类拓扑异构酶 I (topoisomerase I) 抑制剂，可用于癌症研究。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。

生物活性    
Genz-644282 is a non-camptothecin topoisomerase I inhibitor, used for cancer research.

IC50 & Target[1]    
Topoisomerase I

体外研究
(In Vitro)    
Genz-644282 is a topoisomerase I inhibitor. Genz-644282 shows potent activities against 29 human tumor cell lines with IC50s ranging from 1.8 nM to 1.8 μM[1]. Genz-644282 suppresses the PPTP cell lines, with IC50s of 0.2-21.9 nM, and the mean IC50 value is 1.2 nM[2]. Genz-644282 is potent at trapping Top1-DNA covalent cleavage complexes. Genz-644282 (0.1 μM) induces γH2AX foci in human colon cancer HCT116 cells and breast cancer MCF7 cells. Genz-644282 is cytotoxic on the CPT-resistant human cancer cell lines[3].

体内研究
(In Vivo)    
Genz-644282 (1-4 mg/kg) is active when administered intravenously to the mice. Genz-644282 (2.7 mg/kg, i.v.) causes tumor growth delay (TGD) of 34 days in the human HCT-116 colon cancer xenograft, 27 days in the human HT-29 colon carcinoma xenograft and mice bearing the NCI-H460 human non-small cell lung carcinoma. Genz-644282 (2 mg/kg, i.v.) results in a TGD of 33 days in the human HCT-15 colon carcinoma xenograft, and 28 days in mice bearing LOX-IMVI melanoma. Moreover, Genz-644282 (1 mg/kg, i.v.) leads to 14 days of TGD in mice bearing the DLD-1 human colon carcinoma xenograft. Genz-644282 (1.7 mg/kg, i.v.) also produces a TGD of 23 days in mice bearing 786-O tumors and 33 days in NCI-H1299 human non-small cell lung carcinoma xenograft[1]. Genz644282 at maximum tolerated dose (MTD, 4 mg/kg) results in maintained complete responses (MCR) in 6/6 evaluable solid tumor models. Genz644282 (2 mg/kg) induces CR or MCR in 3/3 tumor models and causes objective regressions in 7 of 17 (41%) models, but there are no objective responses at 1 mg/kg[2].

分子量    
407.42

性状    
Solid

Formula    
C22H21N3O5

CAS 号    
529488-28-6

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

溶解性数据    
In Vitro: 
DMSO : 3.64 mg/mL (8.93 mM; ultrasonic and warming and heat to 75°C)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.4545 mL    12.2723 mL    24.5447 mL
5 mM    0.4909 mL    2.4545 mL    4.9089 mL
10 mM    ---    ---    ---
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (protect from light)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
 

参考文献

[1]. Kurtzberg LS, et al. Genz-644282, a novel non-camptothecin topoisomerase I inhibitor for cancer treatment. Clin Cancer Res. 2011 May 1;17(9):2777-87.  [Content Brief] [2]. Houghton PJ, et al. Testing of the topoisomerase 1 inhibitor Genz-644282 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012 Feb;58(2):200-9.  [Content Brief] [3]. Sooryakumar D, et al. Molecular and cellular pharmacology of the novel noncamptothecin topoisomerase I inhibitor Genz-644282. Mol Cancer Ther. 2011 Aug;10(8):1490-9.  [Content Brief]

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