Smoothened agonist

Smoothened agonist

Systematic (IUPAC) name
3-chloro-N-[(1r,4r)-4-(methylamino)cyclohexyl]-N-[3-(pyridin-4-yl)benzyl]benzo[b]thiophene-2-carboxamide
Identifiers
CAS Number	912545-86-9 364590-63-6 (hydrochloride)
PubChem	CID 5284330
ChemSpider	21541484
Chemical data
Formula	C28H28ClN3OS
Molar mass	490.06 g/mol
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]

References

1. 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.
2. 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.
3. 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.
4. 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.