Allosteric Inhibitors

Allosteric Kinase Inhibitors Library encompasses a collection of approximately 26,000 compounds that specifically target allosteric pockets of kinases. These small-molecule kinase inhibitors have proven to be invaluable in targeted therapeutics for treating various human diseases, with a particular focus on cancer.

Traditional small-molecule kinase inhibitors primarily fall under two categories: type I or type II inhibitors that target the ATP-binding pocket of kinases. However, due to the high degree of structural and sequential similarity among ATP pockets, selectively inhibiting kinases becomes a challenging task. To overcome this obstacle and address issues such as poor selectivity and development of drug resistance, researchers propose targeting allosteric pockets of kinases outside the highly conserved ATP pocket. Allosteric inhibitors bind to these alternative pockets and modulate the kinase’s activity through non-competitive mechanisms.

While the number of identified allosteric inhibitors is relatively small compared to those targeting the ATP pocket, the past decade has witnessed encouraging progress in this field. Noteworthy achievements include the FDA approval of the first small-molecule allosteric inhibitor, trametinib, in 2013. Additionally, more than 10 other allosteric inhibitors have advanced to clinical trials, demonstrating their potential therapeutic value. Furthermore, a pipeline of highly selective and potent preclinical molecules in the development stage shows promise for future therapeutic applications.

Allosteric Kinase Inhibitors Library provides a diverse and extensive collection of compounds that target allosteric pockets of kinases. This library presents researchers with a valuable resource to explore novel avenues for the development of kinase inhibitors with enhanced selectivity and efficacy. It holds the potential to overcome current challenges associated with traditional kinase inhibitors, contributing to the advancement of targeted therapeutics, particularly in the treatment of cancer and other diseases.