GSM-1 is a potent γ-secretase modulator. GSM-1 directly targets the transmembrane domain (TMD) 1 of presenilin 1 (PS1)[1][2].
GSM-1 increases the levels of Aβ38 produced from WT APP. GSM-1 potently loweres the levels of Aβ42 of WT APP and all the Phe mutants by ∼70-80%, even for the V44F mutant, which produced only extremely small amounts of Aβ42[1].GSM-1 directly binds to the N-terminal fragment of PS1[2].
[1]. Richard M, et al. Beta-amyloid Precursor Protein Mutants Respond to Gamma-Secretase Modulators. J Biol Chem. 2010 Jun 4;285(23):17798-810.
[2]. Yu Ohki, et al. Phenylpiperidine-type γ-secretase Modulators Target the Transmembrane Domain 1 of Presenilin 1. EMBO J. 2011 Oct 14;30(23):4815-24.