VG-3927

VG-3927 is a potent, orally bioavailable small molecule agonist of the triggering receptor expressed on myeloid cells 2 (TREM2), developed by Vigil Neuroscience for the treatment of neurodegenerative diseases, with an initial focus on Alzheimer's disease. It acts as both a TREM2 agonist and a positive allosteric modulator (PAM), amplifying microglial functional responses at sites of pathology to enhance neuroprotection. VG-3927 is brain penetrant and designed to stimulate microglial proliferation and phagocytic function without increasing inflammation, promoting clearance of aggregated amyloid and tau proteins. Unlike antibody-based TREM2 agonists, it does not bind soluble TREM2 or have an Fc domain, potentially reducing risks such as amyloid-related imaging abnormalities (ARIA). Preclinical studies show that VG-3927 reduces pathological forms of Aβ, insoluble ApoE levels, and peri-plaque dystrophic neurites in animal models. Clinical data indicate favorable safety and pharmacokinetics suitable for daily dosing; ongoing trials are assessing its efficacy in Alzheimer's disease patients[1][2][3][4][5][6][7][8].

Other names

Small Molecule TREM2 Agonist