WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407108
CAS#: 912545-86-9 (free base)
Description: 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.
Hodoodo Cat#: H407108
Name: SAG (Smo agonist) free base
CAS#: 912545-86-9 (free base)
Chemical Formula: C28H28ClN3OS
Exact Mass: 489.16
Molecular Weight: 490.060
Elemental Analysis: C, 68.63; H, 5.76; Cl, 7.23; N, 8.57; O, 3.26; S, 6.54
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:
| Biological target: | SAG is a potent Smoothened (Smo) receptor agonist (EC50=3 nM; Kd=59 nM). |
| In vitro activity: | SAG binds to Smo directly and leads to circumvent receptor-mediated activation. The reduced expression of Pax6, Nkx6.1 and Hb9 in Cdo−/− cells (Fig. 3a) was nearly restored similarly to the level of Cdo+/+cells when SAG was treated (Fig. 4a). Additionally, the expression of Chx10 was even higher in Cdo−/− cells at MNS-5 and Olig2 was significantly eleva-ted in Cdo−/− cells at Elong, compared to that of Cdo+/+ cells. Even though the level of Pax2 and Lbx1 was still higher in Cdo−/− cells at MNS-5 compared to Cdo+/+ cells, the expression of Brn3a and Pax3 was significantly reduced in Cdo−/− cells at MNS-5 (Fig. 4b). Reference: Int J Stem Cells. 2020; 13(3): 342–352. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691856/ |
| In vivo activity: | Maternal administration of SAG caused dose-dependent dysmorphology, as observed in GD 15 fetuses, but did not affect the number of live or resorbed fetuses. Preaxial polydactyly was the most frequent defect, but mild edema and eye anomalies were also observed in a few fetuses (Figure 2A). In a separate preliminary study, these non-limb defects and especially wavy ribs were common and more severe when SAG was administered at GD 8.5, illustrating that as expected, embryo age at the time of exposure is important for the specific developmental effects of SAG. Reference: Birth Defects Res. 2017 Jan 20; 109(1): 49–54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388559/ |
| Solvent | Max Conc. mg/mL | Max Conc. 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 |
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. 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: | 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. |
| In vivo protocol: | 1. 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. |
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