| Abstract: | A novel conjugate of docetaxel and biotin (designated as IDD-1010) was designed and chemically synthesized via an ester linkage at position 2’ carbon in docetaxel. The synthesized pure IDD-1010 exhibits a potent anti-cancer activity in in vitro and in vivo studies. At 10 nM, IDD-1010 has induced increased apoptosis and mitotic arrest of PC3-Luc prostate cancer cells, causing aneuploidy and cell death at higher concentrations. Toxicology studies indicate that the maximal tolerated dose (MTD) of IDD-1010 is 150 mg/kg in mice; equivalent to about 12.2 mg/kg of body weight, or to about an 850 mg dose for a patient weighing 70 kg. The MTD-treated mice exhibited weight gain similar to that of the control group, with no gross pathological signs at 14 days post-dosing. At a lower dose, IDD-1010 treatment did not lead to any significant weight loss in mice, although decreased the tumor volume stemming from injecting cancer cells into the dorsal loop of mouse prostate, and it was found to be more potent than Paclitaxel (reference drug). Similarly, IDD-1010 treatment significantly reduced tumor weight and thereby increased the percentage of mice survival as compared to reference drug-treated and control groups. To summarize, the described experiments using IDD-1010, as compared to the reference drug, strongly suggest a potential treatment utility with a wider therapeutic window for prostate cancer. Henceforth, clinical research on such a novel drug candidate would be greatly worthwhile. |
