Drug intelligence / Profile preview

monSTIM1

Development stage
Preclinical
Lead developer
Gwangju Institute of Science and Technology
Modality
Gene Therapies
Administration
Parenteral
01

Overview

monSTIM1 is an optogenetic actuator designed to modulate intracellular calcium signaling by activating the store-operated calcium entry (SOCE) pathway. It consists of a monomeric fragment of the **Stromal Interaction Molecule 1 (STIM1)** protein, typically the cytoplasmic C-terminal domain (such as the SOAR/CAD domain), fused to a light-sensitive module like **Cryptochrome 2 (CRY2)**. Upon exposure to blue light, the light-sensitive modules undergo oligomerization, which clusters the attached STIM1 fragments. This clustering mimics the natural activation of endogenous STIM1, allowing it to bind and activate **Orai1** calcium channels on the plasma membrane, thereby inducing a transient influx of Ca2+. In preclinical research, particularly in models of **Alzheimer's disease**, monSTIM1 is used to selectively enhance astrocytic calcium influx, which has been shown to reduce amyloid-beta pathology, mitigate sleep disturbances, and modulate tonic GABA currents in the brain.

Other names
monomeric STIM1 optogenetic actuatorlight-activated STIM1
02

Targets

POST (Partner of stromal interaction molecule 1)ORAI3 (Calcium release-activated calcium channel protein 3)ORAI2 (Orai calcium release-activated calcium modulator 2)ORAI1 (Calcium release–activated calcium channel protein 1)

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