Smoothened agonist

Smoothened agonist
Identifiers

IUPAC name 3-chloro-N-[(1r,4r)-4-(methylamino)cyclohexyl]-N-[3-(pyridin-4-yl)benzyl]benzo[b]thiophene-2-carboxamide
CAS Number	912545-86-9^N 364590-63-6 (hydrochloride)
PubChem (CID)	5284330
ChemSpider	21541484^Y
Chemical and physical data
Formula	C₂₈H₂₈ClN₃OS
Molar mass	490.06 g/mol
3D model (Jmol)	Interactive image
SMILES ClC1=C(C(N([C@H]2CC[C@H](NC)CC2)CC3=CC=CC(C4=CC=NC=C4)=C3)=O)SC5=CC=CC=C51
InChI InChI=1S/C28H28ClN3OS/c1-30-22-9-11-23(12-10-22)32(28(33)27-26(29)24-7-2-3-8-25(24)34-27)18-19-5-4-6-21(17-19)20-13-15-31-16-14-20/h2-8,13-17,22-23,30H,9-12,18H2,1H3/t22-,23- Key:VFSUUTYAEQOIMW-YHBQERECSA-N

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's 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

↑ Lewis C, Krieg PA (August 2013). "Reagents for developmental regulation of Hedgehog signaling". Methods. 66: 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.
↑ 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. 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. PMID 27672740.

This article is issued from Wikipedia - version of the 10/6/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.