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]
References[edit]
- ^ Lewis C, Krieg PA (August 2013). "Reagents for developmental regulation of Hedgehog signaling". Methods. 66 (3): 390–397. doi:10.1016/j.ymeth.2013.08.022. PMID 23981360.
- ^ Bragina O, Sergejeva S, Serg M, Zarkovsky T, Maloverjan A, Kogerman P, Zarkovsky A (September 2010). "Smoothened agonist augments proliferation and survival of neural cells". Neurosci. Lett. 482 (2): 81–5. doi:10.1016/j.neulet.2010.06.068. PMID 20600593. S2CID 24186568.
- ^ Heine VM, Griveau A, Chapin C, Ballard PL, Chen JK, Rowitch DH (October 2011). "A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury". Sci Transl Med. 3 (105): 105ra104. doi:10.1126/scitranslmed.3002731. PMC 3694585. PMID 22013124.
- ^ Das I, Park JM, Shin JH, Jeon SK, Lorenzi H, Linden DJ, Worley PF, Reeves RH (September 2013). "Hedgehog agonist therapy corrects structural and cognitive deficits in a down syndrome mouse model". Sci Transl Med. 5 (201): 201ra120. doi:10.1126/scitranslmed.3005983. PMC 4006719. PMID 24005160.
- ^ Lubik AA, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, Cox ME, Li N, Guns ES, Yenki P, Pham S, Buttyan R (2016). "Paracrine Sonic Hedgehog Signaling Contributes Significantly to Acquired Steroidogenesis in the Prostate Tumor Microenvironment". International Journal of Cancer. 140 (2): 358–369. doi:10.1002/ijc.30450. PMID 27672740. S2CID 2354209.