| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| 25mg | |||
| Other Sizes |
| Targets |
Tubulin; STAT3; HIF-1α
ENMD-1198 targets tubulin, a key component of the cytoskeleton, by binding to the colchicine site. This binding disrupts microtubule dynamics, leading to mitotic arrest and apoptosis. Additionally, ENMD-1198 inhibits the activity of hypoxia-inducible factor 1-alpha (HIF-1α) and signal transducer and activator of transcription 3 (STAT3) in human hepatocellular carcinoma (HCC) cells. It also targets angiogenesis, the formation of new blood vessels, by inhibiting the activity of tyrosine kinase receptors involved in this process. |
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| ln Vitro |
The HCC cell growth is significantly inhibited by ENMD-1198 (0-5 μM; 24 hours) with IC50s of 2.5 μM for HUH-7 and HepG2 cells, respectively[3]. The phosphorylation of Akt (HUH-7), FAK (HUH-7), p44/42 MAPK (HepG2), and STAT3 (HUH-7, HepG2) produced by EGF is abolished by ENMD-1198 (2.5 μM; 16 hours)[3].
In vitro, ENMD-1198 exhibits antiproliferative activity against various cancer cell lines. It has been shown to inhibit HIF-1α and STAT3 activity in human hepatocellular carcinoma (HCC) cells. The compound's mechanism involves disrupting microtubule dynamics and inducing cell cycle arrest, which leads to reduced tumor cell proliferation. It is also a potent inhibitor of angiogenesis in vitro. |
| ln Vivo |
Hepatocellular carcinoma growth is efficiently inhibited by ENMD-1198 (200 mg/kg; po; daily from day 7 to day 19) both through direct effects on the tumor cells and by inhibition of angiogenesis[3].
In vivo, ENMD-1198 effectively inhibits the growth of hepatocellular carcinoma through direct effects on tumor cells and through inhibition of angiogenesis. In animal models, oral administration of ENMD-1198 (daily from day 7 to day 19) has been shown to lead to reduced tumor growth and vascularization. The compound's dual mechanism of action, targeting both tumor cells and the tumor vasculature, contributes to its antitumor efficacy. |
| Enzyme Assay |
In cell-free assays, ENMD-1198's activity as a tubulin-binding agent is evaluated by measuring its ability to inhibit tubulin polymerization. Purified tubulin is incubated with varying concentrations of the compound, and the extent of polymerization is monitored spectrophotometrically (turbidity at 340 nm). The IC50 for inhibition of tubulin polymerization is determined from the concentration-response curve. The compound's binding to the colchicine site can be confirmed by competition assays with [3H]colchicine.
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| Cell Assay |
Cell Viability Assay[3]
Cell Types: HUH-7 and HepG2 cells Tested Concentrations: 0-5 μM Incubation Duration: 24 hrs (hours) Experimental Results: Led to a significant dose-dependent inhibition of HCC cell growth. Western Blot Analysis[3] Cell Types: HUH-7 and HepG2 cells Tested Concentrations: 2.5 μM Incubation Duration: 16 hrs (hours) Experimental Results: Abrogated EGF-induced phosphorylation of Akt (HUH-7), FAK (HUH-7), p44/42 MAPK (HepG2), and STAT3 (HUH-7, HepG2). In vitro cell-based experiments with ENMD-1198 typically involve culturing cancer cell lines such as hepatocellular carcinoma (HCC) cells (e.g., HepG2, Huh7). Cells are treated with various concentrations of the compound for 48-72 hours, and cell viability is assessed using MTT or SRB assays. The effect on HIF-1α and STAT3 activity is measured by Western blot or by using reporter gene assays. The anti-angiogenic activity is assessed using endothelial cell tube formation assays or migration assays. |
| Animal Protocol |
Animal/Disease Models: Eight-week- old male athymic nude mice (BALB/c nu/nu) (xenografted hepatocellular tumors)[3]
Doses: 200 mg/kg Route of Administration: Po; daily from day 7 to day 19 Experimental Results: Led to a significant growth inhibition of xenografted hepatocellular tumors . In vivo animal experiments with ENMD-1198 typically involve xenograft models in immunodeficient mice. Mice are inoculated with hepatocellular carcinoma cells to establish tumors. When tumors reach a certain size, animals are treated with ENMD-1198 via oral administration (daily from day 7 to day 19). Tumor volumes are measured periodically, and at the end of the study, tumors are excised for histology and analysis of HIF-1α, STAT3, and angiogenesis markers. |
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for ENMD-1198. As a research compound, its absorption, distribution, metabolism, and excretion (ADME) properties have not been extensively characterized. It is administered orally in in vivo studies. Its bioavailability, half-life, and tissue distribution have not been well established in the available literature.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for ENMD-1198. In preclinical studies, the compound has been shown to reduce tumor growth and vascularization without significant toxicity. The compound is for research use only and is not intended for human therapeutic applications. Further studies would be needed to fully characterize its safety profile.
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| References |
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| Additional Infomation |
Drug Indication
ENMD-1198 has been investigated for the treatment of cancer/tumors (unspecified) and solid tumors. Mechanism of Action ENMD-1198 is a novel chemical entity (NCE) based on a modified 2-methoxyestradiol (2ME2) chemical structure designed to reduce its metabolism while retaining multiple mechanisms of action of 2ME2, including inducing apoptosis, disrupting microtubules, and inhibiting HIF-1α. Preclinical studies have shown that ENMD-1198 is an orally effective antimitotic agent that induces tumor cell division arrest and apoptosis. It also possesses anti-angiogenic activity, further enhancing its overall antitumor effect. ENMD-1198 is a novel antimitotic agent of the 2-methoxyestradiol class. It is a tubulin-binding agent that also inhibits HIF-1α and STAT3 activity. The compound is also known as ENMD1198. It has been investigated for the treatment of hepatocellular carcinoma and other cancers. It is not approved for clinical use and is available for research purposes only. |
| Molecular Formula |
C20H25NO2
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|---|---|
| Molecular Weight |
311.42
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| Exact Mass |
311.189
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| CAS # |
864668-87-1
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| PubChem CID |
11483754
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| Appearance |
White to yellow solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
516
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| Defined Atom Stereocenter Count |
4
|
| SMILES |
C[C@]12CC[C@H]3[C@H]([C@@H]1CC=C2)CCC4=CC(=C(C=C34)OC)C(=O)N
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| InChi Key |
YQJWOUQGXATDAE-ACNBBOPNSA-N
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| InChi Code |
InChI=1S/C20H25NO2/c1-20-8-3-4-17(20)14-6-5-12-10-16(19(21)22)18(23-2)11-15(12)13(14)7-9-20/h3,8,10-11,13-14,17H,4-7,9H2,1-2H3,(H2,21,22)/t13-,14+,17-,20-/m0/s1
|
| Chemical Name |
(8S,9S,13R,14S)-2-methoxy-13-methyl-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthrene-3-carboxamide
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| Synonyms |
ENMD 1198 ENMD1198 ENMD 1198
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| 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 | 3.2111 mL | 16.0555 mL | 32.1110 mL | |
| 5 mM | 0.6422 mL | 3.2111 mL | 6.4222 mL | |
| 10 mM | 0.3211 mL | 1.6055 mL | 3.2111 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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