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Drug intelligence / Profile preview
SIK activator
- Development stage
- Preclinical
- Lead developer
- Massachusetts General Hospital
- Modality
- Small Molecules
01
Overview
SIK activator refers to a class of small-molecule compounds designed to enhance or restore the activity of Salt-Inducible Kinases (SIK1, SIK2, and SIK3). In physiological signaling, SIK activity is suppressed when protein kinase A (PKA) phosphorylates SIK, promoting its binding to inhibitory 14-3-3 chaperone proteins. SIK activators function by blocking these 14-3-3-pSIK interactions, thereby maintaining SIKs in their active state. Restoring SIK activity has shown preclinical promise in mitigating fibrous dysplasia (FD) phenotypes driven by GNAS mutations (such as Gnas R201H), which constitutively activate cAMP-PKA signaling and suppress SIKs. In bone marrow stromal cells, pharmacological SIK activation helps rescue osteogenic and profibrotic abnormalities, offering a novel therapeutic strategy for rare bone diseases.
- Other names
- Salt-inducible kinase activatorsmall-molecule SIK activator
02
Targets
SFN (Protein kinase C inhibitor protein 1)SIK1 (Salt-inducible kinase 1)SIK2 (Salt inducible kinase 2)SIK3
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