Chemistry:Smoothened agonist
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| Formula | C28H28ClN3OS |
| Molar mass | 490.06 g·mol−1 |
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Smoothened agonist (SAG) was one of the first small-molecule agonists developed for the protein Smoothened,[1] a key part of the hedgehog signaling pathway, which is involved in brain development as well as having a number of other functions in the body.
Smoothened agonist has been shown to aid proliferation and survival of developing neurons,[2] and prevent drug-induced brain injury.[3] When injected into the cerebellum of newborn mice with an induced Down syndrome-like condition, Smoothened agonist was able to stimulate normal cerebellum development, resulting in significant behavioural improvement once the mice had grown to adulthood.[4]
Smoothened Agonist was capable of inducing androgen production in both prostate and bone stromal cells that was significantly greater than even similarly treated prostate cancer cells.[5]
The substance has been used as part of a chemical cocktail to turn old and senescent human cells back into young ones (as measured by transcriptomic age), without turning them all the way back into undifferentiated stem cells.[6]
References
- ↑ "Reagents for developmental regulation of Hedgehog signaling". Methods 66 (3): 390–397. August 2013. doi:10.1016/j.ymeth.2013.08.022. PMID 23981360.
- ↑ "Smoothened agonist augments proliferation and survival of neural cells". Neurosci. Lett. 482 (2): 81–5. September 2010. doi:10.1016/j.neulet.2010.06.068. PMID 20600593.
- ↑ "A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury". Sci Transl Med 3 (105): 105ra104. October 2011. doi:10.1126/scitranslmed.3002731. PMID 22013124.
- ↑ "Hedgehog agonist therapy corrects structural and cognitive deficits in a down syndrome mouse model". Sci Transl Med 5 (201): 201ra120. September 2013. doi:10.1126/scitranslmed.3005983. PMID 24005160.
- ↑ "Paracrine Sonic Hedgehog Signaling Contributes Significantly to Acquired Steroidogenesis in the Prostate Tumor Microenvironment". International Journal of Cancer 140 (2): 358–369. 2016. doi:10.1002/ijc.30450. PMID 27672740.
- ↑ "Chemically induced reprogramming to reverse cellular aging". Aging 15 (13): 5966–5989. July 2023. doi:10.18632/aging.204896. PMID 37437248.
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