Fatty acid-binding protein-5 (FABP5) or epidermal FABP belongs to a low molecular weight lipid binding protein family. FABP5 is involved in binding, storing, and transporting hydrophobic ligands to the proper cellar compartment. Recent studies have suggested that FABP5 play important roles in regulation of gene expression associated with with cell growth and differentiation. FABP5 expression level was closely related to malignency in several types of cancers. The functions of FABP5 in modulation of cellular signaling have been studies and suggested that FABP5 is involved in EGFR, NFkB and PPAR pathways. Using IMTACTM (Isobaric Mass Tagged Affinity Characterization)toscreen small molecule library in live cancer cells, ligands covalently bound to FABP5 were identified. Our initial characterization of compounds showed that they specifically bind to FABP5 and inhibit cancer cell growth. These FABP5-specific covalent small molecule ligands will provide a valuable pharmacological tool to dissect FABP5 functions and shed light on the therapeutic potential of targeting FABP5 for the treatment of cancer and metabolic disorders.

Citation Format: Hang Chen, Heather Ha, Robert Stanley, Cindy Huang, Qian Cai, Irene Yuan, Ping Cao. Discovery of BGS1954, a covalent small molecule ligand of FABP5 using IMTACTM platform [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A135. doi:10.1158/1535-7163.TARG-19-A135