title: Identification of a small molecule inhibitor of serine 276 phosphorylation of the p65 subunit of NF-kappaB using in silico molecular docking.
abstract: NF-kappaB is activated in many types of cancer. Phosphorylation of p65 at serine 276 is required for the expression of a subset of NF-kappaB 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.
authors.affiliation: Department of Pharmacology and Therapeutics, Shands Cancer Center, University of Florida, Gainesville, FL 32610-3633, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Law
authors.forename: Patrick
authors.initials: P
authors.lastname: Corsino
authors.forename: Nicole Teoh
authors.initials: NT
authors.lastname: Parker
authors.forename: Brian K
authors.initials: BK
authors.lastname: Law
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D010768:Phosphoserine / Q000037:antagonists & inhibitors / Q000378:metabolism; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D017362:Cyclic AMP Response Element-Binding Protein; D018076:DNA, Complementary; D016209:Interleukin-8; D016328:NF-kappa B; D021122:Protein Subunits; D012334:RNA, Neoplasm; D019010:Vascular Cell Adhesion Molecule-1; D010768:Phosphoserine