SAG hydrochloride

• CAT Number: I019696
• CAS Number: 2095432-58-7
• Molecular Formula: C28H29Cl2N3OS
• Molecular Weight: 526.52
• Purity: ≥95%
• Synonyms: 3-chloro-N-[4-(methylamino)cyclohexyl]-N-[(3-pyridin-4-ylphenyl)methyl]-1-benzothiophene-2-carboxamide;hydrochloride
• InChI: InChI=1S/C28H28ClN3OS.ClH/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;1H
• InChIKey: CRWTYWYPPITOOZ-UHFFFAOYSA-N
• SMILES: CNC1CCC(CC1)N(CC2=CC(=CC=C2)C3=CC=NC=C3)C(=O)C4=C(C5=CC=CC=C5S4)Cl.Cl

SAG hydrochloride is a potent Smoothened (Smo) receptor agonist (EC50=3 nM; Kd=59 nM). SAG hydrochloride activates the Hedgehog signaling pathway and counteracts Cyclopamine (HY-17024) inhibition of Smo[1][2][3].
SAG (0.1 nM-100 μM; 30 h) induces firefly luciferase expression in Shh-LIGHT2 cells with an EC50 of 3 nM and then inhibits expression at higher concentrations[1].
SAG (1-1000 nM; 1 h) competes for the binding of BODIPY-cyclopamine to Smo-expressing Cos-1 cells, yielding an apparent dissociation constant (Kd) of 59 nM for the SAG/Smo complex[1].
SAG (100 nM) inhibits the inhibitory effect of ShhN-induced pathway activation by Robotnikinin[2].
SAG (250 nM; 48 h) significantly increases SMO mRNA and protein expression in MDAMB231 cells[3].
SAG (250 nM; 24 and 48 h) increases CAXII mRNA expression in MDAMB231 cells at 24h in normoxic and hypoxic conditions in MDAMB231 cells[3].
SAG (250 nM; 24 h) increases MDAMB231 cells migration[3].
SAG (1.0 mM) induces more osteogenesis mainly at the defect borders and a significant increase in BV/TV at the eight week timepoint in CD-1 mice[4].
SAG (15-20 mg/kg; i.p.) induces pre-axial polydactyly prevalently in a dose-dependent manner in mice[5].

Reference

[1]. Chen JK, et al. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6.
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[2]. Stanton BZ, et al. A small molecule that binds Hedgehog and blocks its signaling in human cells. Nat Chem Biol. 2009 Mar;5(3):154-6.
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[3]. Guerrini G, et, al. Inhibition of smoothened in breast cancer cells reduces CAXII expression and cell migration. J Cell Physiol. 2018 Dec; 233(12): 9799-9811.
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[4]. Lee S, et al. Combining Smoothened Agonist (SAG) and NEL-like protein-1 (NELL-1) Enhances Bone Healing. Plast Reconstr Surg. 2017 Feb 13.
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[5]. Fish EW, et al. Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice. Birth Defects Res A Clin Mol Teratol. 2016 Nov 1.
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