SAG HCl | CAS#2095432-58-7 | Smo receptor agonist

MedKoo Cat#: 407942 | Name: SAG HCl

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 HCl

CAS#2095432-58-7 (HCl)

Theoretical Analysis

MedKoo Cat#: 407942

Name: SAG HCl

CAS#: 2095432-58-7 (HCl)

Chemical Formula: C28H29Cl2N3OS

Exact Mass: 0.0000

Molecular Weight: 526.52

Elemental Analysis: C, 63.87; H, 5.55; Cl, 13.47; N, 7.98; O, 3.04; S, 6.09

Price and Availability

Size	Price	Availability
1mg	USD 375.00	2 weeks
5mg	USD 600.00	2 weeks
10mg	USD 850.00	2 weeks
25mg	USD 1,200.00	2 weeks
50mg	USD 1,500.00	2 weeks

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Related CAS #

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

Synonym

SAG hydrochloride; SAG; SAG (Smo agonist);

IUPAC/Chemical Name

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

InChi Key

CRWTYWYPPITOOZ-HFSDZXIBSA-N

InChi Code

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/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.[H]Cl

Appearance

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 and water

Shelf Life

>3 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

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	21.7	41.16
	Water	25.0	47.48

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 526.52 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: Geyer N, Ridzewski R, Bauer J, Kuzyakova M, Dittmann K, Dullin C, Rosenberger A, Schildhaus HU, Uhmann A, Fulda S, Hahn H. Different Response of Ptch Mutant and Ptch Wildtype Rhabdomyosarcoma Toward SMO and PI3K Inhibitors. Front Oncol. 2018 Sep 25;8:396. doi: 10.3389/fonc.2018.00396. eCollection 2018. PubMed PMID: 30319965; PubMed Central PMCID: PMC6168716. 2: Guerrini G, Criscuoli M, Filippi I, Naldini A, Carraro F. Inhibition of smoothened in breast cancer cells reduces CAXII expression and cell migration. J Cell Physiol. 2018 Dec;233(12):9799-9811. doi: 10.1002/jcp.26947. Epub 2018 Aug 21. PubMed PMID: 30132883. 3: Gigante ED, Long AB, Ben-Ami J, Caspary T. Hypomorphic Smo mutant with inefficient ciliary enrichment disrupts the highest level of vertebrate Hedgehog response. Dev Biol. 2018 May 15;437(2):152-162. doi: 10.1016/j.ydbio.2018.03.019. Epub 2018 Mar 20. PubMed PMID: 29571613; PubMed Central PMCID: PMC5903954. 4: Zhang F, Hao M, Jin H, Yao Z, Lian N, Wu L, Shao J, Chen A, Zheng S. Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis. Br J Pharmacol. 2017 Mar;174(5):409-423. doi: 10.1111/bph.13701. Epub 2017 Jan 31. PubMed PMID: 28052321; PubMed Central PMCID: PMC5301045. 5: Choi H, Shin JH, Kim ES, Park SJ, Bae IH, Jo YK, Jeong IY, Kim HJ, Lee Y, Park HC, Jeon HB, Kim KW, Lee TR, Cho DH. Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model. PLoS One. 2016 Dec 12;11(12):e0168025. doi: 10.1371/journal.pone.0168025. eCollection 2016. PubMed PMID: 27941997; PubMed Central PMCID: PMC5152889. 6: 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. PubMed PMID: 27801979; PubMed Central PMCID: PMC5388559. 7: Lubik AA, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, Cox ME, Li N, Guns ES, Yenki P, Pham S, Buttyan R. Paracrine sonic hedgehog signaling contributes significantly to acquired steroidogenesis in the prostate tumor microenvironment. Int J Cancer. 2017 Jan 15;140(2):358-369. doi: 10.1002/ijc.30450. Epub 2016 Oct 20. PubMed PMID: 27672740. 8: Wang LC, Almazan G. Role of Sonic Hedgehog Signaling in Oligodendrocyte Differentiation. Neurochem Res. 2016 Dec;41(12):3289-3299. Epub 2016 Sep 17. PubMed PMID: 27639396. 9: Fleury A, Hoch L, Martinez MC, Faure H, Taddei M, Petricci E, Manetti F, Girard N, Mann A, Jacques C, Larghero J, Ruat M, Andriantsitohaina R, Le Lay S. Hedgehog associated to microparticles inhibits adipocyte differentiation via a non-canonical pathway. Sci Rep. 2016 Mar 24;6:23479. doi: 10.1038/srep23479. PubMed PMID: 27010359; PubMed Central PMCID: PMC4806302. 10: Chapouly C, Yao Q, Vandierdonck S, Larrieu-Lahargue F, Mariani JN, Gadeau AP, Renault MA. Impaired Hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: implication in diabetes. Cardiovasc Res. 2016 Feb 1;109(2):217-27. doi: 10.1093/cvr/cvv263. Epub 2015 Dec 8. PubMed PMID: 26645982. 11: Kharebava G, Rashid MA, Lee JW, Sarkar S, Kevala K, Kim HY. N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons. Biol Open. 2015 Nov 6;4(12):1660-70. doi: 10.1242/bio.013425. PubMed PMID: 26545965; PubMed Central PMCID: PMC4736029. 12: Spann AL, Yuan K, Goliwas KF, Steg AD, Kaushik DD, Kwon YJ, Frost AR. The presence of primary cilia in cancer cells does not predict responsiveness to modulation of smoothened activity. Int J Oncol. 2015 Jul;47(1):269-79. doi: 10.3892/ijo.2015.3006. Epub 2015 May 15. PubMed PMID: 25997440. 13: Lian N, Jiang Y, Zhang F, Jin H, Lu C, Wu X, Lu Y, Zheng S. Curcumin regulates cell fate and metabolism by inhibiting hedgehog signaling in hepatic stellate cells. Lab Invest. 2015 Jul;95(7):790-803. doi: 10.1038/labinvest.2015.59. Epub 2015 May 4. PubMed PMID: 25938627. 14: Wang C, Wu H, Evron T, Vardy E, Han GW, Huang XP, Hufeisen SJ, Mangano TJ, Urban DJ, Katritch V, Cherezov V, Caron MG, Roth BL, Stevens RC. Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs. Nat Commun. 2014 Jul 10;5:4355. doi: 10.1038/ncomms5355. PubMed PMID: 25008467; PubMed Central PMCID: PMC4198951. 15: Huang JG, Shen CB, Wu WB, Ren JW, Xu L, Liu S, Yang Q. Primary cilia mediate sonic hedgehog signaling to regulate neuronal-like differentiation of bone mesenchymal stem cells for resveratrol induction in vitro. J Neurosci Res. 2014 May;92(5):587-96. doi: 10.1002/jnr.23343. Epub 2014 Jan 24. PubMed PMID: 24464877. 16: Werminghaus P, Haase M, Hornsby PJ, Schinner S, Schott M, Malendowicz LK, Lammers BJ, Goretzki PE, Müller-Mattheis V, Markus Giessing, Willenberg HS. Hedgehog-signaling is upregulated in non-producing human adrenal adenomas and antagonism of hedgehog-signaling inhibits proliferation of NCI-H295R cells and an immortalized primary human adrenal cell line. J Steroid Biochem Mol Biol. 2014 Jan;139:7-15. doi: 10.1016/j.jsbmb.2013.09.007. Epub 2013 Sep 21. PubMed PMID: 24063979. 17: Gorojankina T, Hoch L, Faure H, Roudaut H, Traiffort E, Schoenfelder A, Girard N, Mann A, Manetti F, Solinas A, Petricci E, Taddei M, Ruat M. Discovery, molecular and pharmacological characterization of GSA-10, a novel small-molecule positive modulator of Smoothened. Mol Pharmacol. 2013 May;83(5):1020-9. doi: 10.1124/mol.112.084590. Epub 2013 Feb 28. Erratum in: Mol Pharmacol. 2013 Aug;84(2):303. PubMed PMID: 23448715. 18: Luo QF, Chen W, Zhang ST. Identification of Nedd4 as a novel regulator in Hedgehog signaling. Chin Med J (Engl). 2012 Nov;125(21):3851-5. PubMed PMID: 23106887. 19: Caparrós-Martín JA, Valencia M, Reytor E, Pacheco M, Fernandez M, Perez-Aytes A, Gean E, Lapunzina P, Peters H, Goodship JA, Ruiz-Perez VL. The ciliary Evc/Evc2 complex interacts with Smo and controls Hedgehog pathway activity in chondrocytes by regulating Sufu/Gli3 dissociation and Gli3 trafficking in primary cilia. Hum Mol Genet. 2013 Jan 1;22(1):124-39. doi: 10.1093/hmg/dds409. Epub 2012 Oct 1. PubMed PMID: 23026747. 20: Yang S, Wang C. The intraflagellar transport protein IFT80 is required for cilia formation and osteogenesis. Bone. 2012 Sep;51(3):407-17. doi: 10.1016/j.bone.2012.06.021. Epub 2012 Jul 4. PubMed PMID: 22771375; PubMed Central PMCID: PMC3412883.