| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Smo, SmoM2[1]
SMANT hydrochloride targets Smoothened (Smo), a seven-transmembrane receptor that is the key transducer of the Hedgehog (Hh) signaling pathway. The compound specifically inhibits the accumulation of Smo within primary cilia (PC), a critical step in Hh signal transduction. Primary cilia are microtubule-based organelles that serve as signaling hubs for the Hh pathway. SMANT hydrochloride is equally effective against SmoM2, the oncogenic, constitutively active form of Smo, and wild-type Smo. By blocking Smo localization to primary cilia, the compound prevents downstream Hh signaling through the Gli family of transcription factors, providing a novel mechanism of Smo inhibition distinct from traditional Smo antagonists. |
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| ln Vitro |
SMANT hydrochloride (0-10 μM, NIH/3T3 cells) inhibits the accumulation of Smo induced by Hh at the primary cilium (IC50: 1.1 μM)[1]. SMANT hydrochloride (0-10 μM, NIH/3T3 cells) inhibits the stimulatory action of SAG in the Gli-luciferase assay and inhibits Smo and SmoM2 activity[1]. Hydrochloride SMANT (0-10 μM) suppresses the growth of cerebellar granule-cell neural progenitors (CGNP) stimulated by Shh and isolated from Ptch1+/− neonates[1].
In vitro studies have demonstrated that SMANT hydrochloride is a potent inhibitor of Smo signaling. The compound blocks Smo accumulation within primary cilia, preventing Hh pathway activation. SMANT hydrochloride is equally active against both wild-type Smo and the oncogenic SmoM2 mutant. This is a significant advantage, as SmoM2 is a common mutation that confers resistance to traditional Smo antagonists. In cell-based assays using Hh-responsive cell lines, SMANT hydrochloride inhibits Gli-dependent transcription and downstream target gene expression. The compound's unique mechanism of action makes it a valuable tool for studying Smo function and for developing therapies that overcome Smo inhibitor resistance. |
| ln Vivo |
In vivo activity data for SMANT hydrochloride is limited in the available literature, as the compound is primarily used as a research tool in cell-based studies. The compound's ability to inhibit SmoM2 suggests it could have therapeutic potential in cancers driven by Smo mutations that are resistant to first-generation Smo inhibitors. However, comprehensive in vivo efficacy studies have not been extensively reported. The compound's utility for in vivo studies would require further characterization of its pharmacokinetic properties and formulation optimization.
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| Enzyme Assay |
Cell-free biochemical assays for SMANT hydrochloride typically measure Smo binding or inhibition of Smo-mediated signaling. A standard protocol involves radioligand binding assays using [³H]-cyclopamine or other Smo ligands. Membranes from Smo-expressing cells are incubated with varying concentrations of SMANT hydrochloride (0.1-100 μM) and the radioligand, and bound radioactivity is measured by scintillation counting. Alternatively, cell-free assays can assess the effects of the compound on Smo conformation or interaction with downstream components. IC₅₀ values are determined from competition binding curves using nonlinear regression analysis. Assays are performed in triplicate with appropriate controls.
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| Cell Assay |
Cellular assays for SMANT hydrochloride typically use Hh-responsive cell lines to assess inhibition of Smo signaling and Smo localization to primary cilia. A standard protocol involves culturing cells (e.g., NIH3T3 fibroblasts or Shh-Light2 cells) on coverslips in 24-well plates, treating with SMANT hydrochloride at concentrations ranging from 0.1-100 μM for 1-24 hours. Smo localization to primary cilia is assessed by immunofluorescence microscopy using antibodies against Smo and ciliary markers (e.g., acetylated tubulin, Arl13b). Hh signaling activity is assessed using Gli-luciferase reporter assays or by measuring expression of Gli target genes (e.g., Gli1, PTCH1) by qPCR.
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| Animal Protocol |
In vivo studies with SMANT hydrochloride are limited, as the compound is primarily a research tool for in vitro applications. If conducted, a typical protocol might involve administration of the compound to rodents by intraperitoneal or oral administration, followed by assessment of Smo localization and Hh signaling in target tissues. Tissues would be collected at various time points and analyzed for Smo ciliary localization by immunohistochemistry and for Hh target gene expression by qPCR. However, comprehensive in vivo efficacy studies have not been extensively reported for this compound.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for SMANT hydrochloride is limited, as the compound is primarily used in research settings. The compound's molecular weight is 375.73 g/mol. The hydrochloride salt form suggests reasonable aqueous solubility. For in vivo applications, the compound would likely require formulation to enhance bioavailability. The compound is typically dissolved in DMSO for in vitro studies. Metabolism and clearance pathways have not been extensively characterized.
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| Toxicity/Toxicokinetics |
Toxicological data specific to SMANT hydrochloride is limited, as the compound is a research chemical used primarily in in vitro settings. At effective concentrations (micromolar range for Smo inhibition), the compound does not show significant cytotoxicity in most cell types. Higher concentrations may have off-target effects or cytotoxicity. The compound's unique mechanism of action—inhibiting Smo ciliary accumulation rather than direct Smo antagonism—suggests a potentially different toxicity profile compared to traditional Smo antagonists. Standard laboratory safety precautions should be observed when handling this compound.
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| References | |
| Additional Infomation |
SMANT hydrochloride is a research compound and not an approved drug. No clinical trials or regulatory approvals exist for this compound. It is commercially available from various suppliers for research use only. The compound's primary value lies in its utility as a pharmacological tool for studying Smo function and Hh signaling, particularly the role of Smo localization to primary cilia. Its equal activity against SmoM2 and wild-type Smo makes it a valuable tool for studying mechanisms of resistance to Smo inhibitors and for developing next-generation Hh pathway inhibitors that can overcome resistance mutations.
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| Molecular Formula |
C16H24BRCLN2O
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|---|---|
| Molecular Weight |
375.73
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| Exact Mass |
374.076
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| CAS # |
1177600-74-6
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| PubChem CID |
2900213
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| Appearance |
White to off-white solid powder
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| LogP |
4.568
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
306
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1CC(CN(C1)CCC(=O)NC2=CC=C(C=C2)Br)C.Cl
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| InChi Key |
XQESCHFXROUCOQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H23BrN2O.ClH/c1-12-9-13(2)11-19(10-12)8-7-16(20)18-15-5-3-14(17)4-6-15;/h3-6,12-13H,7-11H2,1-2H3,(H,18,20);1H
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| Chemical Name |
N-(4-bromophenyl)-3-(3,5-dimethylpiperidin-1-yl)propanamide;hydrochloride
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 83.33 mg/mL (221.78 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.54 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 20.8 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: ≥ 2.08 mg/mL (5.54 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6615 mL | 13.3074 mL | 26.6149 mL | |
| 5 mM | 0.5323 mL | 2.6615 mL | 5.3230 mL | |
| 10 mM | 0.2661 mL | 1.3307 mL | 2.6615 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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