Identification of a small molecule inhibitor of serine 276 phosphorylation of the p65 subunit of NF-κB using in silico molecular docking

Law, Mary; Corsino, Patrick; Parker, Nicole Teoh; Law, Brian K.

doi:10.1016/j.canlet.2009.10.015

« Previous Next »Cancer Letters
Volume 291, Issue 2 , Pages 217-224, 28 May 2010

Identification of a small molecule inhibitor of serine 276 phosphorylation of the p65 subunit of NF-κB using in silico molecular docking

Department of Pharmacology and Therapeutics, Shands Cancer Center, University of Florida, Gainesville, FL 32610-3633, United States

Received 14 May 2009; received in revised form 16 October 2009; accepted 20 October 2009. published online 12 November 2009.

Abstract

NF-κB is activated in many types of cancer. Phosphorylation of p65 at serine 276 is required for the expression of a subset of NF-κB regulated genes, including vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8). Thus, inhibition of serine 276 phosphorylation may prevent metastasis and angiogenesis in certain tumor types. Using in silico molecular docking, small molecules that are predicted to bind to a structural pocket near serine 276 were identified. One compound, NSC-127102, hinders serine 276 phosphorylation and the expression of IL-8 and VCAM-1. Small molecules such as NSC-127102 may be optimized for the future treatment of cancer.

Keywords: NF-κB, p65, TNF-α, IL-8, In silico molecular docking, Serine 276