SAG (Smo agonist) free base| CAS#912545-86-9 | SMO agonist

MedKoo Cat#: 407108 | Name: SAG (Smo agonist) free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SAG is a potent Smoothened (Smo) receptor agonist (Kd = 59 nM); sag antagonizes cyclopamine action at the Smo receptor. SAG potently activates the Hedgehog signaling pathway in Shh-light 2 cells (EC50 ~ 3 nM). SAG induces pathway activation independently of Ptch proteins. The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumours.

Chemical Structure

SAG (Smo agonist) free base

CAS#912545-86-9 (free base)

Theoretical Analysis

MedKoo Cat#: 407108

Name: SAG (Smo agonist) free base

CAS#: 912545-86-9 (free base)

Chemical Formula: C28H28ClN3OS

Exact Mass: 489.1642

Molecular Weight: 490.06

Elemental Analysis: C, 68.63; H, 5.76; Cl, 7.23; N, 8.57; O, 3.26; S, 6.54

Price and Availability

Size	Price	Availability
10mg	USD 125.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 425.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,250.00	Ready to ship
1g	USD 3,250.00	Ready to ship
2g	USD 5,850.00	Ready to ship

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Related CAS #

2095432-58-7 (HCl) 912545-86-9 (free base)

Synonym

SAG; SAG free base; SAG (Smo agonist); SAG (cyclopamine antagonist);

IUPAC/Chemical Name

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

InChi Key

VFSUUTYAEQOIMW-YHBQERECSA-N

InChi Code

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-

SMILES Code

O=C(C1=C(Cl)C2=CC=CC=C2S1)N([C@H]3CC[C@H](NC)CC3)CC4=CC=CC(C5=CC=NC=C5)=C4

Appearance

Off-white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

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

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#SSC51028

QC Data

View QC data: current batch, Lot#SSC51028

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SAG is a Smo receptor agonist (EC50 = 3 nM; Kd = 59 nM). SAG activates the Hedgehog signaling pathway and counteracts Cyclopamine inhibition of Smo.

In vitro activity:

Reactivation of Shh signalling pathway by SAG restored motor neuron specification in Cdo-/- embryonic stem cells. SAG restored immature electrical features of Cdo-/- embryonic stem cells-derived neurons. Reference: Int J Stem Cells. 2020; 13(3): 342–352. https://pubmed.ncbi.nlm.nih.gov/32840224/

In vivo activity:

This study investigated how maternal treatment with SAG affected developing limbs in embryos. SAG treatment led to dose-dependent preaxial polydactyly, with varying degrees of thumb duplication or finger-like digit formation on the preaxial side of the thumb. This effect was observed in a significant percentage of embryos treated with the highest SAG dose. Additionally, SAG treatment increased the expression of Gli1 and Gli2 mRNA in the limb bud. Reference: Birth Defects Res. 2017 Jan 20; 109(1): 49–54. https://pubmed.ncbi.nlm.nih.gov/27801979/

	Solvent	mg/mL	mM
Solubility
	DMSO	35.7	72.79
	DMF	20.0	40.81
	Ethanol	20.0	40.81
	Ethanol:PBS (pH 7.2) (1:1)	0.5	1.02

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 490.06 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Kim H, Lee SY, Jeong HJ, Kang JS, Cho H, Leem YE. Cdo Is Required for Efficient Motor Neuron Generation of Embryonic Stem Cells. Int J Stem Cells. 2020 Nov 30;13(3):342-352. doi: 10.15283/ijsc20037. PMID: 32840224; PMCID: PMC7691856. 2. Peng WX, Zhu SL, Zhang BY, Shi YM, Feng XX, Liu F, Huang JL, Zheng SG. Smoothened Regulates Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Activation of Rho GTPase Signaling. Front Immunol. 2017 Feb 15;8:159. doi: 10.3389/fimmu.2017.00159. PMID: 28261216; PMCID: PMC5309251. 3. Burton DF, Boa-Amponsem OM, Dixon MS, Hopkins MJ, Herbin TA, Toney S, Tarpley M, Rodriguez BV, Fish EW, Parnell SE, Cole GJ, Williams KP. Pharmacological activation of the Sonic hedgehog pathway with a Smoothened small molecule agonist ameliorates the severity of alcohol-induced morphological and behavioral birth defects in a zebrafish model of fetal alcohol spectrum disorder. J Neurosci Res. 2022 Aug;100(8):1585-1601. doi: 10.1002/jnr.25008. Epub 2022 Jan 11. PMID: 35014067; PMCID: PMC9271529. 4. Fish EW, Parnell SE, Sulik KK, Baker LK, Murdaugh LB, Lamson D, Williams KP. Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice. Birth Defects Res. 2017 Jan 20;109(1):49-54. doi: 10.1002/bdra.23571. PMID: 27801979; PMCID: PMC5388559.

In vitro protocol:

In vivo protocol:

1. Burton DF, Boa-Amponsem OM, Dixon MS, Hopkins MJ, Herbin TA, Toney S, Tarpley M, Rodriguez BV, Fish EW, Parnell SE, Cole GJ, Williams KP. Pharmacological activation of the Sonic hedgehog pathway with a Smoothened small molecule agonist ameliorates the severity of alcohol-induced morphological and behavioral birth defects in a zebrafish model of fetal alcohol spectrum disorder. J Neurosci Res. 2022 Aug;100(8):1585-1601. doi: 10.1002/jnr.25008. Epub 2022 Jan 11. PMID: 35014067; PMCID: PMC9271529. 2. Fish EW, Parnell SE, Sulik KK, Baker LK, Murdaugh LB, Lamson D, Williams KP. Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice. Birth Defects Res. 2017 Jan 20;109(1):49-54. doi: 10.1002/bdra.23571. PMID: 27801979; PMCID: PMC5388559.

1: Fish EW, Boschen KE, Parnell SE. Efcab7 deletion sensitizes mice to the teratogenic effects of gastrulation-stage alcohol exposure. Reprod Toxicol. 2024 Dec;130:108729. doi: 10.1016/j.reprotox.2024.108729. Epub 2024 Oct 2. PMID: 39366525; PMCID: PMC11624995. 2: Zong R, Zheng Y, Yan Y, Sun W, Kong L, Huang Y, Liu Y, Jiang C, Ping J, Li C. Mesenchymal stem cells-derived exosomes alleviate liver fibrosis by targeting Hedgehog/SMO signaling. Hepatol Int. 2024 Aug 13. doi: 10.1007/s12072-024-10717-y. Epub ahead of print. PMID: 39138757. 3: Cui L, Shen Y, Duan S, Ding Q, Wang Y, Yang W, Chen Y. GIMAP7 inhibits epithelial-mesenchymal transition and glycolysis in lung adenocarcinoma cells via regulating the Smo/AMPK signaling pathway. Thorac Cancer. 2024 Feb;15(4):286-298. doi: 10.1111/1759-7714.15150. Epub 2023 Dec 27. PMID: 38151913; PMCID: PMC10834198. 4: Hu L, Gao M, Jiang H, Zhuang L, Jiang Y, Xie S, Zhang H, Wang Q, Chen Q. Triptolide inhibits epithelial ovarian tumor growth by blocking the hedgehog/Gli pathway. Aging (Albany NY). 2023 Oct 17;15(20):11131-11151. doi: 10.18632/aging.205110. Epub 2023 Oct 17. PMID: 37851362; PMCID: PMC10637820. 5: Lin T, Sun Y. Arl13b promotes the proliferation, migration, osteogenesis, and mechanosensation of osteoblasts. Tissue Cell. 2023 Jun;82:102088. doi: 10.1016/j.tice.2023.102088. Epub 2023 Apr 11. PMID: 37058812. 6: Khara LS, Ali DW. The endocannabinoid system's involvement in motor development relies on cannabinoid receptors, TRP channels, and Sonic Hedgehog signaling. Physiol Rep. 2023 Jan;11(1):e15565. doi: 10.14814/phy2.15565. PMID: 36636759; PMCID: PMC9837476. 7: Xu Y, Sun H. Involvement of hedgehog signaling in all-trans retinoic acid- mediated suppression of colon cancer. Am J Transl Res. 2022 Sep 15;14(9):6536-6549. PMID: 36247302; PMCID: PMC9556466. 8: Morii A, Inazu T. HDAC8 is implicated in embryoid body formation via canonical Hedgehog signaling and regulates neuronal differentiation. Biochem Biophys Res Commun. 2022 Nov 12;629:78-85. doi: 10.1016/j.bbrc.2022.08.068. Epub 2022 Sep 1. PMID: 36113181. 9: Hu Z, Chen Y, Zhu S, Feng X, Zhang B, Huang J. Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK Signaling. J Immunol Res. 2022 Jun 22;2022:3423692. doi: 10.1155/2022/3423692. PMID: 35785032; PMCID: PMC9242744. 10: Saeki N, Itoh Y, Kanai R, Itoh S, Inububishi T, Akiyama S, Inui-Yamamoto C, Abe M. Pregnane X receptor (PXR) represses osteoblast differentiation through repression of the Hedgehog signaling pathway. Exp Cell Res. 2022 Jul 1;416(1):113156. doi: 10.1016/j.yexcr.2022.113156. Epub 2022 Apr 11. PMID: 35421365. 11: Del Giovane A, Russo M, Tirou L, Faure H, Ruat M, Balestri S, Sposato C, Basoli F, Rainer A, Kassoussi A, Traiffort E, Ragnini-Wilson A. Smoothened/AMP- Activated Protein Kinase Signaling in Oligodendroglial Cell Maturation. Front Cell Neurosci. 2022 Jan 10;15:801704. doi: 10.3389/fncel.2021.801704. PMID: 35082605; PMCID: PMC8784884. 12: Kozielewicz P, Schulte G. NanoBRET and NanoBiT/BRET-Based Ligand Binding Assays Permit Quantitative Assessment of Small Molecule Ligand Binding to Smoothened. Methods Mol Biol. 2022;2374:195-204. doi: 10.1007/978-1-0716-1701-4_17. PMID: 34562254. 13: Guo K, Wang P, Zhang L, Zhou Y, Dai X, Yan Y, Chen Y, Wasan HS, Yu J, Ruan S, Sun L. Transcription factor POU4F2 promotes colorectal cancer cell migration and invasion through hedgehog-mediated epithelial-mesenchymal transition. Cancer Sci. 2021 Oct;112(10):4176-4186. doi: 10.1111/cas.15089. Epub 2021 Aug 10. PMID: 34327778; PMCID: PMC8486210. 14: Xie L, Ji X, Tu Y, Wang K, Zhu L, Zeng X, Wang X, Zhang J, Zhu M. MLN4924 inhibits hedgehog signaling pathway and activates autophagy to alleviate mouse laser-induced choroidal neovascularization lesion. Biomed Pharmacother. 2020 Oct;130:110654. doi: 10.1016/j.biopha.2020.110654. Epub 2020 Sep 1. PMID: 34321162. 15: Hor CHH, Lo JCW, Cham ALS, Leong WY, Goh ELK. Multifaceted Functions of Rab23 on Primary Cilium-Mediated and Hedgehog Signaling-Mediated Cerebellar Granule Cell Proliferation. J Neurosci. 2021 Aug 11;41(32):6850-6863. doi: 10.1523/JNEUROSCI.3005-20.2021. Epub 2021 Jul 1. PMID: 34210780; PMCID: PMC8360682. 16: Ding F, Yang S. Epigallocatechin-3-gallate inhibits proliferation and triggers apoptosis in colon cancer via the hedgehog/phosphoinositide 3-kinase pathways. Can J Physiol Pharmacol. 2021 Sep;99(9):910-920. doi: 10.1139/cjpp-2020-0588. Epub 2021 Feb 22. PMID: 33617370. 17: Qu JY, Xiao YT, Zhang YY, Xie HT, Zhang MC. Hedgehog Signaling Pathway Regulates the Proliferation and Differentiation of Rat Meibomian Gland Epithelial Cells. Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):33. doi: 10.1167/iovs.62.2.33. PMID: 33616621; PMCID: PMC7910630. 18: Qi X, Friedberg L, De Bose-Boyd R, Long T, Li X. Sterols in an intramolecular channel of Smoothened mediate Hedgehog signaling. Nat Chem Biol. 2020 Dec;16(12):1368-1375. doi: 10.1038/s41589-020-0646-2. Epub 2020 Sep 14. PMID: 32929279; PMCID: PMC7669734. 19: Kim H, Lee SY, Jeong HJ, Kang JS, Cho H, Leem YE. Cdo Is Required for Efficient Motor Neuron Generation of Embryonic Stem Cells. Int J Stem Cells. 2020 Nov 30;13(3):342-352. doi: 10.15283/ijsc20037. PMID: 32840224; PMCID: PMC7691856. 20: Li SJ, Mei QH, Zeng SY, Lai LL, Quan J, Zhang X. Protective effect of sonic hedgehog signaling pathway activation on acute myocardial infarction. J Biol Regul Homeost Agents. 2020 Mar-Apr;34(2):367-378. doi: 10.23812/19-451-A-64. PMID: 32515175.