| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
EC50: 0.3 nM (Hh)[1].
Hedgehog agonist 1 targets the Hedgehog (Hh) signaling pathway, a highly conserved developmental pathway that plays critical roles in embryonic development, tissue patterning, and stem cell maintenance. The Hedgehog pathway is activated by the binding of Hedgehog ligands (Sonic, Indian, and Desert Hedgehog) to the Patched (Ptch) receptor, which relieves the inhibition of Smoothened (Smo), leading to the activation of GLI transcription factors. Hedgehog agonist 1 acts as a potent agonist of the Hedgehog pathway with an EC50 of 0.3 nM. By activating the Hedgehog pathway, the compound promotes the expression of Hedgehog target genes, which are involved in cell proliferation, differentiation, and survival. The compound's oral bioavailability and brain penetrance make it suitable for studying Hedgehog signaling in the central nervous system. |
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| ln Vitro |
In vitro, Hedgehog agonist 1 is a potent Hedgehog pathway agonist with an EC50 of 0.3 nM. The compound's activity can be measured in cell-based assays using Hedgehog-responsive reporter cell lines, such as NIH3T3 cells stably transfected with a GLI-responsive luciferase reporter. Cells are treated with varying concentrations of Hedgehog agonist 1, and luciferase activity is measured to determine the EC50. The compound's potency (EC50 = 0.3 nM) demonstrates its high efficacy at activating the Hedgehog pathway. Hedgehog agonist 1 can be used for research on stroke and other neurological disorders, as Hedgehog signaling is involved in neuroprotection and neural repair.
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| ln Vivo |
In vivo, Hedgehog agonist 1 is orally bioavailable and brain penetrant, making it suitable for studies in the central nervous system. The compound can be used for research on stroke and other neurological disorders. By activating the Hedgehog pathway, the compound may promote neuroprotection, neural repair, and tissue regeneration following ischemic injury. However, specific animal model studies, dosing regimens, and quantitative outcomes have not been extensively reported in the available literature. Further in vivo studies would be required to fully characterize its efficacy, safety, and pharmacokinetic properties in animal models of stroke and other neurological disorders.
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| Cell Assay |
In vitro cell-based assay protocols for Hedgehog agonist 1 typically involve assessing its activation of the Hedgehog signaling pathway using reporter cell lines. A standard protocol would involve seeding Hedgehog-responsive reporter cells (e.g., NIH3T3 cells stably transfected with a GLI-responsive luciferase reporter) in multi-well plates. Cells are treated with varying concentrations of Hedgehog agonist 1 (typically 0.001 nM to 10 μM) for 24-48 hours. Luciferase activity is measured using a luminescent substrate, and EC50 values are determined from concentration-response curves. For studies of neuroprotection, primary neuronal cultures or neuronal cell lines can be treated with the compound, and cell survival, neurite outgrowth, and gene expression can be assessed. Appropriate controls include vehicle-treated cells and cells treated with a known Hedgehog antagonist for comparison.
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| Animal Protocol |
In vivo animal experimental protocols for Hedgehog agonist 1 would typically involve administering the compound to animal models of stroke or other neurological disorders. A standard protocol for stroke studies might involve inducing ischemic stroke in rodents (e.g., by middle cerebral artery occlusion, MCAO) and then administering Hedgehog agonist 1 orally or intraperitoneally at doses determined from preliminary studies. The compound's oral bioavailability and brain penetrance make oral administration feasible. Endpoints would include infarct volume measurement, neurological score assessment, evaluation of neuronal survival and regeneration, and assessment of Hedgehog pathway activation in brain tissue. Appropriate controls would include vehicle-treated groups and sham-operated groups.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Hedgehog agonist 1 indicate that the compound is orally bioavailable and brain penetrant. It has a molecular weight of 556.07 and a molecular formula of C29H28ClF2N3O2S. Specific PK parameters such as half-life, Cmax, AUC, volume of distribution, and clearance have not been extensively reported. The compound's metabolism, protein binding, and routes of elimination remain to be characterized. Further pharmacokinetic studies would be required to understand its absorption, distribution, metabolism, and excretion profile. The compound is intended for research use only and is not intended for human use.
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| References | |
| Additional Infomation |
Hedgehog agonist 1 (compound 21k, SAG 21k) is a research-grade compound that functions as a potent Hedgehog pathway agonist with an EC50 of 0.3 nM. It is orally bioavailable and brain penetrant and can be used for research on stroke and other neurological disorders. The compound has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action involves activation of the Hedgehog signaling pathway, promoting cell proliferation, differentiation, and survival. The compound is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
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| Molecular Formula |
C29H28CLF2N3O2S
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|---|---|
| Molecular Weight |
556.07
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| Exact Mass |
555.155
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| CAS # |
946002-48-8
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| PubChem CID |
16678532
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
707.9±60.0 °C at 760 mmHg
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| Flash Point |
381.9±32.9 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.651
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| LogP |
6.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
38
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| Complexity |
785
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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(CC1=CC(C3C=CN=CC=3)=CC=C1OC)[C@@H]1CC[C@@H](NC)CC1)=O)S2
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| InChi Key |
YVIFQUJDZSAFKG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H28ClF2N3O2S/c1-33-20-4-6-21(7-5-20)35(29(36)28-26(30)25-22(31)8-9-23(32)27(25)38-28)16-19-15-18(3-10-24(19)37-2)17-11-13-34-14-12-17/h3,8-15,20-21,33H,4-7,16H2,1-2H3
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| Chemical Name |
3-chloro-4,7-difluoro-N-[(2-methoxy-5-pyridin-4-ylphenyl)methyl]-N-[4-(methylamino)cyclohexyl]-1-benzothiophene-2-carboxamide
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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 :~40 mg/mL (~71.93 mM; with sonication (<60°C))
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up 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 (4.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 and add it to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7983 mL | 8.9917 mL | 17.9833 mL | |
| 5 mM | 0.3597 mL | 1.7983 mL | 3.5967 mL | |
| 10 mM | 0.1798 mL | 0.8992 mL | 1.7983 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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