An inhibitor of tubulin polymerization
D-64131 is a novel inhibitor of Tubulin polymerization that competitively binds with [(3)H]colchicine to αβ-Tubulin. IC50 Value: N/ATarget: Microtubule/Tubulinin vitro: D-64131 is cytotoxic and inhibits tumor cell proliferation in vitro (IC50 = 74 nM). D-64131 prevents growth of tumor models in mice following oral administration in vivo. D-64131 has significant potential in cancer treatment. The proliferation of tumor cells from 12 of 14 different organs and tissues was inhibited with mean IC(50)s of 62 nM by D-64131.in vivo: In animal studies, no signs of systemic toxicity were observed after p.o. dosages of up to 400 mg/kg of D-64131. In xenograft experiments with the human amelanoic melanoma MEXF 989, D-64131 was highly active with treatment resulting in a growth delay of 23.4 days at 400 mg/kg. Therefore, D-64131 and analogues have the potential to be developed for cancer therapy, replacing or supplementing standard therapy regimens with tubulin-targeting drugs from natural sources.
参考文献:
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