Therapeutic for treatment of cancer.
- The first in class, potent and selective agonists of Bax with nanomolar activity.
- Bax activators have significantly less apoptotic effect on normal cells as compared to cancer cells.
- Compounds have shown high selectivity for tumor cells.
Patients with cancer have poor prognosis due to chemoresistance. Development of more effective, new drugs that act through basic molecular mechanism (i.e. apoptosis) to overcome chemoresistance is essential to improve the prognosis of patients with various types of cancer. Bax is a major, multidomain, proapoptotic member of the Bcl2 family that is widely expressed in various types of cancer. This suggests that Bax may be a potential therapeutic target for cancer treatment and activation of Bax would promote cancer cells to undergo apoptosis.
Bax is a major proapoptotic protein which is required for cell death and functions as a tumor suppressor. Mechanisms involved in the activation of Bax have clinical relevance for cancer therapy. Identifying novel small molecule Bax activators presents a novel strategy to develop new anti-cancer drugs for the treatment. These compounds represent significantly less apoptotic effect on normal cells as compared to cancer cells, indicating a selectivity of these compounds for tumor cells, and have shown to potently suppress the growth of various cisplatin resistant human lung cancer cell lines as well as overcome radioresistance. The compounds have also been shown to be effective against oral and throat cancer cell lines. These novel Bax activators have good potential to be developed as a new class of anticancer drugs for clinical treatment of patients with various types of cancer.
- Second generation Bax activator compounds with nanomolar activity have been developed.
- Compounds are well-tolerated in mouse models of lung cancer.
- Compounds have been shown to have potent anti-tumor activity in lung cancer animal models.