AT-13387 Zytiga Combo

AT-13387 is a novel inhibitor of HSP-90 a chaperone protein which stabilises a number of cellular proteins including the androgen receptor (AR). Upon HSP-90 inhibition the AR undergoes decomposition and cannot function in cell signalling. This interuption of AR stimulated signal transduction results in the death of prostate cancer cells and so HSP-90 inhibitors have therapeutic potential in the treatment of prostate cancer.

Zytiga is now widely used in prostate cancer therapy and a combination trial of AT-13387 with Zytiga is currently underway. AT-13387 is produced by Astex Therapeutics a forward looking new enterprise in oncology with several exciting new lead compounds with promising preclinical anticancer activity. The combination of AT-13387 offers a two pronged approach at blocking androgen receptor mediated prostate cancer growth and should work very well together.

Molecular structure of AT-13387 shows a cresol group which mimics the natural HSP-90 inhibitor salvestrol Q40.

Studies have shown that HSP-90 inhibition with salvestrol Q40 results in degradation of important signal transduction proteins such as the STAT kinases that ultimately leads to apoptosis and cancer cell death. Molecular modelling studies show that salvestrol Q40 inhibits HSP-90 by neatly locking in to the ATP binding site. Therefore HSP-90 inhibitors have promising potential for the treatment of a variety of cancers including prostate cancer and trials of HSP-90 inhibitors against breast cancer also look promising.