thienopyrimidine and indole-2-carboxylic-acid

Members of the antiapoptotic BCL-2 proteins are involved in tumor growth, progression and survival, and are also responsible for chemoresistance to conventional anticancer agents. Early efforts to target these proteins yielded some active compounds; however, newer methodologies involving structure-based drug design, Nuclear Magnetic Resonance (NMR)-based screening and fragment-based screening yielded more potent compounds. Discovery of specific as well as nonspecific inhibitors of this class of proteins has resulted in great advances in targeted chemotherapy and decrease in chemoresistance. Here, we review the history and current progress in direct as well as selective targeting of the BCL-2 proteins for anticancer therapy.

Topics: Aniline Compounds; Antineoplastic Agents; Apoptosis; Arylsulfonates; Binding Sites; Bridged Bicyclo Compounds, Heterocyclic; Carboxylic Acids; Cell Line, Tumor; Cellular Senescence; Drug Screening Assays, Antitumor; Gene Expression Regulation; Humans; Hydrophobic and Hydrophilic Interactions; Hydroxyquinolines; Indoles; Molecular Structure; Molecular Targeted Therapy; Myeloid Cell Leukemia Sequence 1 Protein; Protein Binding; Protein Conformation; Proto-Oncogene Proteins c-bcl-2; Pyrimidines; Pyrogallol; Pyrroles; Salicylates; Structure-Activity Relationship; Sulfonamides