Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Cancer

Cancer

Retinoid X receptor-a (RXRA; RXRa)

In vitro and mouse studies identified derivatives of the generic NSAID sulindac that specifically inhibit RXRa and could help treat cancer. Sulindac derivatives were designed to block the binding between N-terminal-truncated RXRa and phosphoinositide 3-kinase regulatory subunit 1a (PIK3R1; p85a) to inhibit downstream protein kinase B (PKB; PKBA; AKT; AKT1) signaling. In human lung, breast and prostate cancer cell lines, the two lead sulindac derivatives caused greater apoptosis than sulindac. In a mouse xenograft model of hepatocellular carcinoma, the derivatives each decreased tumor growth compared with vehicle. Next steps include safety and toxicity studies of the derivatives.

SciBX 7(17); doi:10.1038/scibx.2014.487
Published online May 1, 2014

Patent application filed; available for licensing

Chen, L. et al. Chem. Biol.; published online April 2, 2014;
doi:10.1016/j.chembiol.2014.02.017
Contact: Ying Su, Sanford-Burnham Medical Research Institute,
La Jolla, Calif.
e-mail:

ysu@sanfordburnham.org
Contact: Xiao-kun Zhang, same affiliation as above
e-mail:

xzhang@sanfordburnham.org