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Pharmacological targeting of BMAL1 modulates circadian and immune pathways.
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ID: paper-40133642
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Pharmacological targeting of BMAL1 modulates circadian and immune pathways.
Pu H, Bailey LC, Bauer LG, Voronkov M, Baxter M, Huber KVM, Khorasanizadeh S, Ray D, Rastinejad F
Abstract
The basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) proteins BMAL1 and CLOCK heterodimerize to form the master transcription factor governing rhythmic gene expression. Owing to connections between circadian regulation and numerous physiological pathways, targeting the BMAL1-CLOCK complex pharmacologically is an attractive entry point for intervening in circadian-related processes. In this study, we developed a small molecule, Core Circadian Modulator (CCM), that targets the cavity in the PASB dom...
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