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 Y 364590-63-6 (hydrochloride)
PubChem CID	5284330
ChemSpider	21541484 Y
UNII	4XN97SZK4J
ChEBI	CHEBI:138438
CompTox Dashboard (EPA)	DTXSID80415294
Chemical and physical data
Formula	C28H28ClN3OS
Molar mass	490.06 g·mol−1
3D model (JSmol)	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, 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, and prevent drug-induced brain injury. 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.

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.

Some analogues of piperazines as a novel class of Smoothened agonists modulates Hedgehog signaling in the crypts of the small intestines by binding to Smoothened and thereby leading to intestinal stem cell compartment expansion, improved intestinal recovery, and survival of lethally irradiated animals.