| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 41 nM (Shh-light2 cells Smo receptors)[1]
MRT-81 targets Smoothened (Smo), the seven-transmembrane receptor that serves as the principal transducer of the Hedgehog (Hh) signaling pathway. In the Hh pathway, Smo is activated upon Hh ligand binding to the Patched receptor, leading to downstream signaling through Gli transcription factors. Smo is a validated therapeutic target in Hh-driven cancers. MRT-81 binds to Smo with high affinity (IC₅₀ = 41 nM in Shh-light2 cells), blocking its activation and subsequent Hh signaling. The compound is active against both human and rodent Smo receptors, making it useful for cross-species studies. MRT-81 has potent Hedgehog inhibitory activity. |
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| ln Vitro |
MRT-81 inhibits the Smo agonist SAG (0.1 μM)-induced differentiation of mesenchymal pluripotent C3H10T1/2 cells into alkaline phosphatasepositive osteoblasts, with an IC50 value of 64 nM[1]. With an IC50 less than 10 nM, MRT-81 (1-1000 nM) is a strong antagonist of SAG (0.01 μM)-induced rat granule cell precursors (GCPs) proliferation[1]. In HEK-hSmo cells, MRT-81 (0, 0.1, 1, 10, 30, 100, 300, 1000 nM; 2 h; 37 °C) inhibits the binding of BODIPY-cyclopamine (5 nM) to hSmo in a dose-dependent manner, with an IC50 of 63 nM[1].
In vitro studies have demonstrated that MRT-81 is a potent antagonist of Smo with an IC₅₀ of 41 nM in Shh-light2 cells. The compound inhibits Hh signaling in various cell-based assays, blocking Gli-dependent transcription and downstream target gene expression. In cancer cell lines driven by Hh signaling, MRT-81 treatment results in reduced cell proliferation. The compound shows activity against both human and rodent Smo receptors, making it valuable for cross-species pharmacology studies. MRT-81's potency and selectivity make it a useful tool for studying Hh signaling and for developing therapies for Hh-driven cancers. |
| ln Vivo |
In vivo activity data for MRT-81 is limited in the available literature, as the compound is primarily used as a research tool in cell-based studies. The compound's potent Smo antagonism (IC₅₀ = 41 nM) suggests it could have therapeutic potential in Hh-driven cancers. However, comprehensive in vivo efficacy studies have not been extensively reported. The compound has been investigated for cancer research applications. Future studies may explore its effects in animal models of Hh-driven malignancies.
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| Enzyme Assay |
Cell-free biochemical assays for MRT-81 typically measure binding to Smo 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 MRT-81 (0.1-1000 nM) and the radioligand, and bound radioactivity is measured by scintillation counting. Alternatively, cell-free assays using Smo activation of downstream components can be used. IC₅₀ values are determined from competition binding curves using nonlinear regression analysis. Assays are performed in triplicate with appropriate positive and negative controls.
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| Cell Assay |
Cellular assays for MRT-81 typically use Hh-responsive cell lines to assess inhibition of Smo signaling. A standard protocol involves culturing Shh-light2 cells or other Hh-responsive cells in 96-well plates, treating with MRT-81 at concentrations ranging from 0.1-1000 nM for 24-48 hours, and stimulating with Shh ligand or Smo agonists. Hh signaling activity is assessed using Gli-luciferase reporter assays or by measuring expression of Gli target genes (e.g., Gli1, PTCH1) by qPCR. Cell proliferation is assessed by MTT or CellTiter-Glo assays. The compound's effects on Smo signaling can be confirmed by assessing Gli transcription factor activity.
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| Animal Protocol |
In vivo studies with MRT-81 are limited, as the compound is primarily a research tool for in vitro applications. If conducted, a typical protocol might involve administration of MRT-81 to rodents by intraperitoneal or oral administration, followed by assessment of Hh signaling in target tissues. Tissues would be collected at various time points and analyzed for Hh target gene expression by qPCR and for tumor growth inhibition in xenograft models. However, comprehensive in vivo efficacy studies have not been extensively reported for this compound.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for MRT-81 is limited, as the compound is primarily used in research settings. The compound's molecular weight is 555.64 g/mol. The compound's physicochemical properties suggest moderate lipophilicity. 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 MRT-81 is limited, as the compound is a research chemical used primarily in in vitro settings. At effective concentrations (41 nM for Smo inhibition), the compound does not show significant cytotoxicity in most cell types. Higher concentrations may have off-target effects or cytotoxicity. As with all Smo antagonists, potential toxicity could arise from inhibition of Hh signaling in tissues where the pathway is important for homeostasis. Standard laboratory safety precautions should be observed when handling this compound.
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| References | |
| Additional Infomation |
MRT-81 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. With an IC₅₀ of 41 nM in Shh-light2 cells, MRT-81 is a potent Smo antagonist that can be used to investigate the roles of Hh signaling in development, cancer, and other biological processes. Its activity against both human and rodent Smo receptors makes it useful for cross-species studies.
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| Molecular Formula |
C31H29N3O5S
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|---|---|
| Molecular Weight |
555.64
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| Exact Mass |
555.182
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| CAS # |
1263132-08-6
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| PubChem CID |
56964692
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| Appearance |
White to light yellow solid powder
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| LogP |
6.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
40
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| Complexity |
831
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C2=CC=CC=C2)=CC=C(C(NC2=CC(NC(=S)NC(=O)C3=CC(OC)=C(OC)C(OC)=C3)=CC=C2C)=O)C=C1
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| InChi Key |
CTXQODCQOSYYDE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H29N3O5S/c1-19-10-15-24(32-31(40)34-30(36)23-16-26(37-2)28(39-4)27(17-23)38-3)18-25(19)33-29(35)22-13-11-21(12-14-22)20-8-6-5-7-9-20/h5-18H,1-4H3,(H,33,35)(H2,32,34,36,40)
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| Chemical Name |
3,4,5-trimethoxy-N-[[4-methyl-3-[(4-phenylbenzoyl)amino]phenyl]carbamothioyl]benzamide
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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: 100 mg/mL (179.97 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 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 to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7997 mL | 8.9986 mL | 17.9973 mL | |
| 5 mM | 0.3599 mL | 1.7997 mL | 3.5995 mL | |
| 10 mM | 0.1800 mL | 0.8999 mL | 1.7997 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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