Titanocene Y

Titanocene Y also known as bis[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride or dichloridobis(η⁵-(p-methoxybenzyl)cyclopentadienyl)titanium is an

Titanocene dichloride is known to be a potential anticancer drug^[2] since the late 1970s. After initial clinical trials against breast and renal-cell cancer were performed with this compound,^[3][4] the search for improved derivatives started.^[5] Particularly, lipophilic titanocene dichloride derivatives derived from fulvenes^[6] were synthesised in structural diversity and this led to the development of bis[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride,^[1] which became better known in the literature under its trivial name of Titanocene Y.

Mechanism of action

Titanocene Y is a cytotoxic apoptosis-inducing^[7] and anti-angiogenic^[8] drug candidate targeting renal-cell cancer and other solid tumors.^[9][10] The compound is transported via serum albumin selectively into cancer cells^[11][12] and targets their DNA by coordinating strongly to phosphate groups.^[13][14] Additionally, Titanocene Y is able to induce apoptosis via the FAS receptor pathway.^[15] Very encouraging is the fact that Titanocene Y is breaking platinum-resistance in human colon and human lung cancer cells,^[16] which might make it attractive as a cytotoxic component of future 2nd or 3rd line cancer treatments.

Animal testing

Titanocene Y was tested extensively in vivo; it showed promising results against xenografted human epidermoid carcinoma^[17] and prostate cancer,^[18] while best results are reached against breast^[19] and renal-cell cancer.^[20] Titanocene Y can be given in the mouse in high dosages and it shows generally mild toxicity in the form of diarrhea. Titanocene Y is not patent protected and would therefore benefit from non-commercial sponsoring to develop it into a cytotoxic drug candidate for the treatment of advanced renal-cell cancer – an area in need of better therapies.

References