SAG, Hedgehog Agonist

SAG is a potent, selective, and cell-permeable small-molecule agonist of the Hedgehog pathway. It modulates the coupling of Smo with its downstream effector by interacting with the Smo heptahelical domain (KD = 59 nM). SAG induces Hedgehog pathway activation with an EC50 of ~3 nM in NIH 3T3-derived Shh-LIGHT2 cells and counteracts Cyclopamine-KAAD inhibition of Smo. It was reported that SAG acts as an activator at low concentrations and as an inhibitor at high concentrations (>1 µM). In recent studies, SAG was shown to prevent glucocorticoid-induced neonatal cerebellar injury, and trigger rapid metabolic rewiring via AMPK.

Product information

CAS Number: 912545-86-9

Molecular Weight: 490.06

Formula: C28H28ClN3OS

Related CAS Number:

364590-63-6 (SAG(trans-cis))

1401532-80-6 (SAG(cis）)

2095432-58-7 (SAG HCl)

2109424-53-3 (SAG(trans-cis) HCl)

Chemical Name: 3-chloro-N-((1r,4r)-4-(methylamino)cyclohexyl)-N-(3-(pyridin-4-yl)benzyl)benzo[b]thiophene-2-carboxamide

Smiles: CN[C@@H]1CC[C@H](CC1)N(CC1C=C(C=CC=1)C1C=CN=CC=1)C(=O)C1SC2=CC=CC=C2C=1Cl

InChiKey: VFSUUTYAEQOIMW-YHBQERECSA-N

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-

Technical Data

Appearance: Powder Solid

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 50 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Powder: 4^oC 1 year

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: DMSO: 4^oC 3 month

Drug Formulation: To be determined

HS Tariff Code: 38200

How to use

In Vitro:

SAG was used at 200 nM to induce Hh pathway activation.

References:

1. Frank-Kamenetsky M, et al. Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists. (2002) Journal of Biology (1): 10.2-10.19.
2. Chen JK, et al. Small molecule modulation of Smoothened activity.(2002) Proc Natl Acad Sci U S A. 99(22):14071-6.
3. Chen W, et al. Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2. (2004) Science. 306(5705):2257-60.
4. Dyer LA, et al. BMP signaling modulates hedgehog-induced secondary heart field proliferation. (2010) Dev Biol. 348(2):167-76.
5. Heine VM, et al. A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury. (2011) Sci Transl Med. 3(105).
6. eperino R, et al. Hedgehog partial agonism drives Warburg-like metabolism in muscle and brown fat. (2012) Cell. 151(2):414-26.

Products are for research use only. Not for human use.