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| 50mg |
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| Targets |
MRT-14 targets Smoothened (Smo), a seven-transmembrane G protein-coupled receptor-like protein that is the central signal transducer of the Hedgehog (Hh) signaling pathway. Smo is activated by the Hh ligand through the Patched receptor and initiates a signaling cascade that leads to the activation of Gli transcription factors, which regulate the expression of genes involved in cell proliferation, differentiation, and survival. Aberrant Hh signaling, often caused by mutations in Smo or Patched, is associated with various cancers, including basal cell carcinoma, medulloblastoma, and pancreatic cancer. By antagonizing Smo, MRT-14 blocks Hh signal transduction, inhibiting the proliferation of Hh-dependent cancer cells.
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| ln Vitro |
In vitro, MRT-14 acts as a potent Smo antagonist. In cell-based assays, the compound inhibits Hh pathway activity, as measured by reduced Gli-dependent reporter gene expression. MRT-14 inhibits the proliferation of cancer cells with aberrant Hh signaling, including those with Smo mutations. The compound's activity is concentration-dependent, with effective concentrations typically in the nanomolar to low micromolar range. Its potent antagonism of Smo makes it a valuable tool for studying Hh signaling and for developing novel therapeutics for Hh-driven cancers. Detailed IC50 values for Smo inhibition are available in published literature.
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| ln Vivo |
In vivo, MRT-14 has been studied in preclinical models of cancers associated with aberrant Hh signaling. The compound's ability to antagonize Smo and block Hh signaling may lead to tumor growth inhibition in animal models of basal cell carcinoma, medulloblastoma, and pancreatic cancer. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. The compound is primarily used as a research tool for studying Hh signaling and cancer biology. Further studies are needed to fully characterize its therapeutic potential, dosing regimens, and safety profile in vivo.
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| Enzyme Assay |
The in vitro Smo antagonism assay for MRT-14 typically uses cells expressing Gli-dependent luciferase reporter constructs (e.g., Shh-Light II cells). Cells are seeded in 96-well plates and treated with varying concentrations of the test compound (typically 1 nM to 10 µM) in the presence or absence of a Smo agonist (e.g., SAG or purmorphamine) for 24-48 hours. Luciferase activity is measured using a luminescence plate reader. The compound's ability to inhibit agonist-induced Hh pathway activation is calculated, and IC50 values are determined from dose-response curves using nonlinear regression. For binding studies, radioligand binding assays using [³H]-SAG or [³H]-cyclopamine can be performed. Positive controls (e.g., cyclopamine, vismodegib) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
For in vitro cellular assays, cancer cell lines with aberrant Hh signaling (e.g., basal cell carcinoma, medulloblastoma, or pancreatic cancer cells) are treated with MRT-14 at concentrations ranging from 1 nM to 10 µM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Hh pathway activity is assessed by measuring Gli1, Gli2, and Ptch1 mRNA levels by qRT-PCR. Protein expression of Gli1 and other Hh targets is assessed by Western blotting. Cell cycle distribution is analyzed by propidium iodide staining and flow cytometry. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. All experiments include appropriate controls (vehicle, known Smo antagonists) and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are used in tumor xenograft models of Hh-driven cancers (e.g., basal cell carcinoma, medulloblastoma, or pancreatic cancer). When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). MRT-14 is administered orally or intraperitoneally at doses ranging from 1 to 50 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study endpoint, tumors are harvested for immunohistochemistry (Ki67, Gli1) and Western blot analysis of Hh pathway markers. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of MRT-14 have been partially characterized. The compound has a molecular weight of 448.47 and a molecular formula of C24H24N4O5. Following oral or intraperitoneal administration, the compound shows moderate absorption with a Tmax of 1-3 hours. Plasma half-life is estimated to be 4-8 hours. The compound distributes into tissues including tumor, liver, and kidney. Plasma protein binding is moderate to high. Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Oral bioavailability is moderate (approximately 30-50%) due to first-pass metabolism. Further PK studies are needed for comprehensive characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of MRT-14 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk appears low based on preliminary studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
MRT-14 is a potent Smo antagonist used to study cancers linked to abnormal Hh signaling, including basal cell carcinoma and pancreatic cancer. It has a molecular formula of C24H24N4O5 and a molecular weight of 448.47. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent (typically ≥98%) for laboratory use only. Its potent antagonism of Smo makes it a valuable tool for studying Hh signaling, cancer biology, and for developing novel therapeutics for Hh-driven cancers.
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| Molecular Formula |
C24H24N4O5
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| Molecular Weight |
448.47
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| Exact Mass |
448.174
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| CAS # |
1263131-83-4
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| PubChem CID |
136210502
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.5
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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 |
33
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| Complexity |
668
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NC=NNC1=CC=CC(NC(=O)C2=CC=CC=C2)=C1)(=O)C1=CC(OC)=C(OC)C(OC)=C1
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| InChi Key |
CIWMWTKJZQOXBC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H24N4O5/c1-31-19-12-16(13-20(32-2)21(19)33-3)23(30)28-24(25)27-18-11-7-10-17(14-18)26-22(29)15-8-5-4-6-9-15/h4-14H,1-3H3,(H,26,29)(H3,25,27,28,30)
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| Chemical Name |
N-[N'-(3-benzamidophenyl)carbamimidoyl]-3,4,5-trimethoxybenzamide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~222.98 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.57 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 (5.57 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 | 2.2298 mL | 11.1490 mL | 22.2980 mL | |
| 5 mM | 0.4460 mL | 2.2298 mL | 4.4596 mL | |
| 10 mM | 0.2230 mL | 1.1149 mL | 2.2298 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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