The serine/threonine kinase glycogen synthase kinase-3β (GSK-3β) plays a multifunctional role through its involvement in multiple signaling pathways. Because of its relevant role in Alzheimer’s disease (AD) pathogenesis, regulating GSK-3β activity has been proposed as a potential approach to target AD-related pathology.

In work conducted by Jining Medical University investigators, synthesis and optimization of a previously reported ATP-competitive pyrrolo[2,3-b]pyridine-based glycogen synthase kinase 3β (GSK-3β) inhibitor led to the discovery of compound [I], a candidate with significant inhibitory activity on GSK-3β (IC50=0.35 nM), with its inhibitory effect being approximately 12-fold greater than that of broad-spectrum GSK-3β inhibitor staurosporine and 189-fold greater than that of the parent compound.

4M Therapeutics Inc. has released new preclinical data for its lead program, 4MT-2001, a novel small-molecule glycogen synthase kinase 3β (GSK-3β) inhibitor, demonstrating central nervous system (CNS) target engagement.

CTNNB1 syndrome is a neurodevelopmental disorder characterized by intellectual disability, global developmental delay, microcephaly and motor disabilities, among others, caused by pathogenic loss-of-function variants in the CTNNB1 gene, which encodes β-catenin. This syndrome has no treatment option, with only supportive care available. To address this unmet medical need, researchers from the Broad Institute and Tufts University School of Biomedical Sciences have developed a Ctnnb1 germline heterozygote murine model that mimics the human CTNNB1 syndrome.

4M Therapeutics Inc. has announced the presentation of preclinical data on its small-molecule glycogen synthase kinase-3β (GSK-3β) inhibitors in models of bipolar disorder.

While an “unexpected placebo effect” marred its primary endpoint, the pivotal phase II/III study testing AMO-02 (tideglusib) showed clinically significant benefits across a range of functional and objective assessments, according to developer Amo Pharma Ltd., which is prepping to meet with regulators to discuss potential approval for use in children and adolescents with congenital myotonic dystrophy type 1 (CDM1), an ultra-rare subtype of myotonic dystrophy type 1 for which no treatment options are available.