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Genz-644282
Cat No.
CEI-1348
Product Overview
Genz-644282 [8,9-dimethoxy-5-(2-N-methylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one] has emerged as a promising candidate of non-Camptothecin topoisomerase I inhibitor for antitumor agents. Clinical trial: Dose-Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Solid Tumors. Phase 1
CAS No.
529488-28-6
Molecular Weight
407.42
Purity
0.98
Storage
Store at -20°C
Synonyms
Genz644282; Genz 644282
Targets
topoisomerase I
IC50
1.2 nM
Molecular Formula
C22H21N3O5
Chemical Name
2,3-dimethoxy-12-(2-(methylamino)ethyl)-[1,3]dioxolo[4,5:4,5]benzo[1,2-h]benzo[c][1,6]naphthyridin-13(12H)-one
Solubility
Soluble in DMSO
Shipping Conditions
Evaluation sample solution: ship with blue ice. All other available size: ship with RT, or blue ice upon request
In vitro
Genz-644282 demonstrated potent cytotoxic activity with a median IC(50) of 1.2nM (range 0.2-21.9nM). Limited cross-resistance to Genz-644282 was also found in the Top1 knockdown colon cancer (HCT116) and breast cancer (MCF7) cell lines and in human adenocarcinoma cells (KB31/KBV1) that overexpress (P-glycoprotein, ABCB1), a member of the ATP-binding cassette family of cell surface transport proteins known to confer MDR.
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. Genz-644282 was tolerated at doses up to 4 mg/kg when administered intravenously on alternate days, and the compound was active at doses from 1 to 4 mg/kg. The efficacy of Genz-644282 was compared with irinotecan in 4 human colon carcinoma xenograft models. In the human HCT-116 colon cancer xenograft, TGD values were 14 days for irinotecan (60 mg/kg) and 34 days for Genz-644282 (2.7 mg/kg), giving maximum test to control ratios (T/Cs) of 23.7% and 16.8%, respectively.
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