The BH3 Mimetic Obatoclax Accumulates in Lysosomes and Causes Their Alkalinization.

Obatoclax belongs to a class of compounds known as BH3 mimetics which function as antagonists of Bcl-2 family apoptosis regulators. It has undergone extensive preclinical and clinical evaluation as a cancer therapeutic. Despite this, it is clear that obatoclax has additional pharmacological effects that contribute to its cytotoxic activity.

Navitoclax augments the activity of carboplatin and paclitaxel combinations in ovarian cancer cells.

Objectives: To evaluate the efficacy of combination of navitoclax, carboplatin and paclitaxel in ovarian cancer.

Methods: 8 ovarian cancer cell lines were treated with either doublet or triplet combinations of navitoclax, carboplatin and paclitaxel. Interactions were assessed by determining a combination index or measuring caspase activity.

Understanding sensitivity to BH3 mimetics: ABT-737 as a case study to foresee the complexities of personalized medicine.

BH3 mimetics such as ABT-737 and navitoclax bind to the BCL-2 family of proteins and induce apoptosis through the intrinsic apoptosis pathway. There is considerable variability in the sensitivity of different cells to these drugs. Understanding the molecular basis of this variability will help to determine which patients will benefit from these drugs.