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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
SAG1.5 targets the Smoothened (Smo) receptor, a key signal transducer in the Hedgehog (Hh) signaling pathway. Smo is a G protein-coupled receptor-like protein that activates downstream signaling cascades leading to the activation of Gli transcription factors. By acting as a potent agonist at Smo with an EC50 of 1 nM and Ki values between 0.5 and 2.3 nM, SAG1.5 activates the Hedgehog pathway. This activation promotes cell proliferation, differentiation, and stem cell reprogramming.
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| ln Vitro |
Significant in vitro expansion of quiescent CD133+ CD45-liver stem cells (Hh3A cells) enriched from undamaged liver is promoted by HhAg1.5 (5 μM; for 3 weeks) [2]. With a Ki value of 0.52 nM, Hh-Ag1.5 binds to Smo-containing membranes in a competitive manner [3]. With an EC50 of 7 nM, the Smo agonist SAG-1.5 has efficacy in the nanomolar range when it comes to stimulating Gli-responsive reporter activity [4].
In vitro, SAG1.5 binds to Smo-containing membranes in a competitive manner with a Ki value of 0.52 nM. It stimulates Gli-responsive reporter activity with an EC50 of 7 nM. The compound promotes significant in vitro expansion of quiescent CD133+ CD45- liver stem cells (Hh3A cells) enriched from undamaged liver at 5 μM for 3 weeks. SAG1.5 induces the differentiation of human induced pluripotent stem cells (hiPSCs) into skin progenitor cells. |
| ln Vivo |
In vivo, SAG1.5-mediated reprogramming breaks the quiescence of non-injured liver stem cells and rescues liver failure. The compound's ability to activate the Hedgehog pathway and promote stem cell proliferation and differentiation suggests potential applications in regenerative medicine and tissue repair. However, specific in vivo efficacy data in animal models are not extensively detailed in the available literature. The compound is a research tool for studying Hedgehog signaling.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for SAG1.5 are radioligand binding assays using membrane preparations from cells expressing recombinant Smo receptor. The compound's binding affinity (Ki) is determined by its ability to displace a labeled Smo ligand. Functional assays such as Gli-responsive reporter assays are used to measure the compound's agonist activity at Smo. The EC50 for stimulation of Gli-responsive reporter activity is determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for SAG1.5 are performed using cell lines that respond to Hedgehog signaling, such as NIH3T3 cells or other Hh-responsive cells. Cells are treated with varying concentrations of SAG1.5, and Hedgehog pathway activation is assessed by measuring Gli-mediated transcription using reporter gene assays. Stem cell proliferation and differentiation are assessed in appropriate stem cell models. These assays confirm the functional agonist activity of SAG1.5 at Smo.
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| Animal Protocol |
In vivo animal experiments for SAG1.5 are conducted in mouse models of liver failure and other conditions. Mice are administered SAG1.5 via oral or intraperitoneal injection, and liver regeneration, stem cell activation, and functional recovery are assessed. Endpoints include assessment of liver function, stem cell markers, and tissue repair. These studies evaluate the compound's ability to activate Hedgehog signaling and promote tissue regeneration in vivo.
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| ADME/Pharmacokinetics |
SAG1.5 has a molecular weight of 526.04 and a molecular formula of C28H26ClF2N3OS. The compound is a white to off-white solid powder with a LogP of 6.5. It is soluble in DMSO and other organic solvents. The compound should be stored as a powder at -20°C for up to 3 years or at 4°C for up to 2 years. In solvent, it is stable at -80°C for 6 months or at -20°C for 1 month.
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| Toxicity/Toxicokinetics |
The toxicological profile of SAG1.5 has not been extensively characterized. As a Hedgehog pathway agonist, the compound may have potential effects on cell proliferation and differentiation, which could be associated with toxicity at high doses. Standard toxicology studies would be necessary to establish its safety profile. No significant toxicity has been reported in the available research literature. The compound is a research tool and is not intended for human use.
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| References |
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| Additional Infomation |
SAG1.5 is a potent Hedgehog pathway agonist that targets the Smoothened (Smo) receptor with an EC50 of 1 nM. It is one of the most potent and selective small-molecule agonists of the Hedgehog pathway. SAG1.5 binds to Smo with Ki values between 0.5 and 2.3 nM and stimulates Gli-responsive reporter activity with an EC50 of 7 nM. The compound mediates reprogramming of liver stem cells and rescues liver failure. SAG1.5 is a research compound and is not an approved drug.
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| Molecular Formula |
C28H26CLF2N3OS
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|---|---|
| Molecular Weight |
526.040351390839
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| Exact Mass |
525.145
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| CAS # |
612542-14-0
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| PubChem CID |
44195701
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| Appearance |
White to off-white solid powder
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| LogP |
6.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
736
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C12=C(F)C=CC(F)=C1C(Cl)=C(C(N([C@@H]1CC[C@@H](NC)CC1)CC1=CC=CC(C3C=CN=CC=3)=C1)=O)S2
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| InChi Key |
RXZDWPYJFCAZCW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H26ClF2N3OS/c1-32-20-5-7-21(8-6-20)34(16-17-3-2-4-19(15-17)18-11-13-33-14-12-18)28(35)27-25(29)24-22(30)9-10-23(31)26(24)36-27/h2-4,9-15,20-21,32H,5-8,16H2,1H3
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| Chemical Name |
3-chloro-4,7-difluoro-N-[4-(methylamino)cyclohexyl]-N-[(3-pyridin-4-ylphenyl)methyl]-1-benzothiophene-2-carboxamide
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| Synonyms |
SAG 1.5; SAG-1.5; SAG1.5
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~95.05 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9010 mL | 9.5050 mL | 19.0100 mL | |
| 5 mM | 0.3802 mL | 1.9010 mL | 3.8020 mL | |
| 10 mM | 0.1901 mL | 0.9505 mL | 1.9010 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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