In-silico screening of new potential Bcl-2/Bcl-xl inhibitors as apoptosis modulators
One of the major problems in the fight against cancer is drug-resistance, which, at a molecular level, can be acquired through mutations able to deactivate apoptosis. In particular, proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-xl and Bcl-2, are overexpressed in many tumours. The development of new inhibitors of these proteins as potential anticancer therapeutics represents a new frontier. In this work, we carried out an in-silico screening of compounds from a free database of more than 2 million structures (ZINC database), which allowed us to identify 17 sulfonamide derivatives as new potential inhibitors; these are currently undergoing biological evaluation.
KeywordsApoptosis Bcl-2 Bcl-xl Inhibitors Molecular docking
- 5.Ligandfit User Manual, Accelrys Inc, 2003.Google Scholar
- 9.Gehlhaar D, Bouzida D, Rejto P (1999) Reduced dimensionality in ligand–protein structure prediction: covalent inhibitors of serine proteases and design of site-directed combinatorial libraries. In: Parrill AL, Reddy MR (eds) Rational drug design: novel methodology and practical applications, vol 719. American Chemical Society, Washington, DC, pp 292–311Google Scholar