Small Molecule Antagonists of NAADP-Induced Ca²⁺ Release in T-Lymphocytes Suggest Potential Therapeutic Agents for Autoimmune Disease.

ABSTRACT: Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca²⁺-releasing second messenger known to date, but the precise NAADP/Ca²⁺ signalling mechanisms are still controversial. We report the synthesis of small-molecule inhibitors of NAADP-induced Ca²⁺ release based upon the nicotinic acid motif. Alkylation of nicotinic acid with a series of bromoacetamides generated a diverse compound library. However, many members were only weakly active or had poor physicochemical properties. Structural optimisation produced the best inhibitors that interact specifically with the NAADP/Ca²⁺ release mechanism, having no effect on Ca²⁺ mobilized by the other well-known second messengers D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P

SUBMITTER: Zhang B 

PROVIDER: S-EPMC6233153 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature