| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
Terameprocol targets the transcription factor Sp1. Sp1 is a sequence-specific DNA-binding protein that regulates the transcription of many genes involved in cell growth, differentiation, and apoptosis. By inhibiting the binding of Sp1 to DNA, Terameprocol suppresses the expression of Sp1-dependent genes. Key target genes include CDC2 (a cell cycle regulator), survivin (an inhibitor of apoptosis), and HMGB1 (a pro-inflammatory cytokine). The inhibition of these genes leads to cell cycle arrest, induction of apoptosis, and inhibition of inflammation. Terameprocol also inhibits the binding of Sp1 to the HIV long terminal repeat promoter and the α-ICP4 promoter, which is essential for HSV replication. This suggests that Terameprocol has potential antiviral activity against HIV and HSV. The compound's mechanism of action is distinct from that of its parent compound, NDGA, as it is a site-specific transcription inhibitor that avoids off-target lipoxygenase inhibition. This selectivity makes Terameprocol a more targeted and potentially safer therapeutic agent. The compound's ability to modulate Sp1-mediated transcription makes it a valuable tool for studying the role of Sp1 in various diseases.
|
|---|---|
| ln Vitro |
Terameprocol demonstrates potent in vitro activity by inhibiting Sp1 transcription factor binding and suppressing the expression of Sp1-dependent genes. It inhibits Sp1 binding at the HIV long terminal repeat promoter with an IC50 of 11 μM and at the α-ICP4 promoter with an IC50 of 43.5 μM. This inhibition leads to the suppression of target genes such as CDC2, survivin, and HMGB1. By reducing the expression of CDC2, a key regulator of the cell cycle, Terameprocol induces cell cycle arrest. By suppressing survivin, an inhibitor of apoptosis, it promotes programmed cell death. By inhibiting HMGB1, a pro-inflammatory cytokine, it reduces inflammation. These combined effects result in antitumorigenic activity. In addition, Terameprocol inhibits the growth of murine and human melanomas and human colon cancer in vivo without causing other tissue toxicity. The compound's ability to specifically inhibit Sp1-mediated transcription, while avoiding off-target lipoxygenase inhibition, makes it a valuable tool for studying Sp1 function and for developing new therapeutic strategies.
|
| ln Vivo |
Terameprocol demonstrates significant in vivo activity, including antitumor, anti-angiogenic, and anti-inflammatory effects. The in vivo growth of xenografts in numerous human tumor types is suppressed upon treatment with Terameprocol. It also inhibits the growth of murine and human melanomas and human colon cancer in vivo without causing other tissue toxicity. These findings highlight its broad-spectrum anti-cancer activity. In addition to its antitumor effects, Terameprocol has been investigated for its potential to treat pulmonary hypertension, where it down-regulates HMGB1, a key mediator of vascular proliferation. The compound's anti-inflammatory and anti-proliferative effects are mediated through the inhibition of Sp1-dependent gene transcription. A Phase I study of Terameprocol has been conducted in patients with advanced leukemias to evaluate its safety and efficacy. These in vivo results demonstrate that Terameprocol is a promising therapeutic agent for various cancers and inflammatory diseases.
|
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cellular) assay for Terameprocol typically involves assessing its ability to inhibit Sp1 transcription factor binding to DNA. In a typical protocol, a DNA fragment containing the Sp1 binding site is incubated with purified Sp1 protein and varying concentrations of Terameprocol. The binding of Sp1 to DNA is then measured using an electrophoretic mobility shift assay (EMSA) or a DNA pull-down assay. The inhibition of Sp1-DNA binding by Terameprocol is used to calculate the IC50 values. For Terameprocol, this method has been used to determine its IC50 of 11 μM for the HIV long terminal repeat promoter and 43.5 μM for the α-ICP4 promoter. These assays are crucial for characterizing the compound's mechanism of action at the molecular level.
|
| Cell Assay |
The in vitro cellular assay for Terameprocol typically involves evaluating its effects on cell viability, apoptosis, and the expression of its target genes. In a typical assay, cancer cells are treated with varying concentrations of Terameprocol for a specified period. Cell viability is then measured using an MTT or similar assay to determine the IC50. To assess apoptosis, cells can be stained with annexin V and propidium iodide and analyzed by flow cytometry. The expression of target genes such as CDC2, survivin, and HMGB1 is measured by Western blot or qPCR. The results show that Terameprocol suppresses the expression of these genes, leading to cell cycle arrest, apoptosis, and inhibition of inflammation. These cellular assays are crucial for confirming the compound's mechanism of action and for evaluating its potency and efficacy in a relevant biological context.
|
| Animal Protocol |
The in vivo animal experimental protocol for Terameprocol typically involves the use of mouse xenograft models of human cancers. In a typical study, immunodeficient mice are implanted with human tumor cells (e.g., melanoma, colon cancer) subcutaneously. When tumors reach a certain size, the mice are treated with Terameprocol, typically via intraperitoneal or oral administration, at various doses and schedules. Tumor volume is measured regularly to assess tumor growth inhibition. The compound's efficacy is evaluated by comparing tumor growth in treated mice to that in vehicle-treated controls. Additionally, tumors can be collected at the end of the study to analyze the expression of Sp1 target genes by immunohistochemistry or Western blot. In a model of pulmonary hypertension, the effect of Terameprocol on vascular remodeling and HMGB1 expression is assessed. These in vivo models are essential for demonstrating the compound's therapeutic potential and for understanding its mechanism of action in a complex biological system.
|
| ADME/Pharmacokinetics |
Specific pharmacokinetic (PK) data for Terameprocol are not detailed in the provided references. However, the compound has been studied in a Phase I clinical trial, indicating that it has been administered to humans and has some level of systemic exposure. Terameprocol is soluble in DMSO but not in water. The powder formulation is stable when stored at -20°C. Further studies are needed to fully characterize the PK properties of Terameprocol, including its absorption, distribution, metabolism, and excretion (ADME) profile.
|
| Toxicity/Toxicokinetics |
Specific toxicity (toxicology) data for Terameprocol are not fully detailed in the provided references. However, the compound has been investigated in a Phase I clinical trial in patients with advanced leukemias, suggesting that it has an acceptable safety profile for human use. In preclinical studies, Terameprocol inhibits the growth of tumors without causing other tissue toxicity. Comprehensive toxicological assessments, including acute and chronic toxicity studies, would be necessary to fully evaluate the safety profile of Terameprocol.
|
| References |
|
| Additional Infomation |
Terameprocol is a lignan. It has been investigated for the treatment of brain and central nervous system tumors. Terameprocol has been reported to be present in Schisandra propinqua, Schisandra rubriflora, and Otoba novogranatensis, with relevant data available. Terameprocol is a synthetic tetramethyl derivative of nordihydroguaiaric acid (NDGA) and is a transcription inhibitor with potential antiviral, anti-angiogenic, and antitumor activities. During DNA synthesis, Terameprocol competes with the transcription factor Sp1 for a specific Sp1 DNA-binding domain within the gene promoter region. In virus-infected cells, blocking the Sp1 binding site inhibits Sp1-regulated viral promoter activity and gene expression, thereby suppressing viral transcription and replication. In tumor cells, this drug works by blocking the Sp1 binding site, interfering with the transcription of Sp1-dependent genes such as cyclin-dependent kinase 2 (Cdc2), survivin, and vascular endothelial growth factor (VEGF), which are overexpressed in various cancers. By inhibiting the transcription of these Sp1-regulated genes, terimepreprol may reduce tumor angiogenesis and tumor cell proliferation, and induce tumor cell apoptosis.
Terameprocol is also known as EM-1421, tetramethyl-nordihydroguaiaretic acid (M4N), and tetra-O-methyl nordihydroguaiaretic acid (TMNDGA). It is a synthetic derivative of NDGA and a non-selective lipoxygenase inhibitor. Terameprocol inhibits Sp1 transcription factor binding and suppresses the expression of Sp1-dependent genes such as CDC2, survivin, and HMGB1, leading to cell cycle arrest, apoptosis, and inhibition of inflammation. It has potential antiviral, anti-angiogenic, and antitumor activities. Terameprocol has been investigated for the treatment of inflammatory diseases, cancers, and pulmonary hypertension. A Phase I study has been conducted in patients with advanced leukemias. The compound has a molecular weight of 358.47 and a molecular formula of C22H30O4. |
| Molecular Formula |
C22H30O4
|
|---|---|
| Molecular Weight |
358.47
|
| Exact Mass |
358.214
|
| CAS # |
24150-24-1
|
| PubChem CID |
476861
|
| Appearance |
White to off-white solid powder
|
| Density |
1.0±0.1 g/cm3
|
| Boiling Point |
458.5±40.0 °C at 760 mmHg
|
| Flash Point |
108.8±34.2 °C
|
| Vapour Pressure |
0.0±1.1 mmHg at 25°C
|
| Index of Refraction |
1.522
|
| LogP |
5.86
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
26
|
| Complexity |
352
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C[C@H](CC1=CC(=C(C=C1)OC)OC)[C@@H](C)CC2=CC(=C(C=C2)OC)OC
|
| InChi Key |
ORQFDHFZSMXRLM-IYBDPMFKSA-N
|
| InChi Code |
InChI=1S/C22H30O4/c1-15(11-17-7-9-19(23-3)21(13-17)25-5)16(2)12-18-8-10-20(24-4)22(14-18)26-6/h7-10,13-16H,11-12H2,1-6H3/t15-,16+
|
| Chemical Name |
4-[(2S,3R)-4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-1,2-dimethoxybenzene
|
| Synonyms |
tetraOmethylNDGA; tetra-O-methyl nordihydroguaiaretic acid. M4N; tetramethyl-nordihydroguaiaretic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~278.96 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7896 mL | 13.9482 mL | 27.8963 mL | |
| 5 mM | 0.5579 mL | 2.7896 mL | 5.5793 mL | |
| 10 mM | 0.2790 mL | 1.3948 mL | 2.7896 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
