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| Targets |
The primary target of NM-3 is vascular endothelial growth factor (VEGF), a key pro-angiogenic growth factor. By inhibiting VEGF, NM-3 prevents the activation of VEGF receptors on endothelial cells, thereby inhibiting endothelial cell proliferation, migration, and tube formation. This anti-angiogenic mechanism reduces the formation of new blood vessels, which is essential for tumor growth and metastasis. NM-3 inhibits angiogenesis with an IC50 of 1 μg/mL (approximately 3.78 μM). The compound's anti-arthritic effects are also attributed to its anti-angiogenic activity, as angiogenesis plays a role in the pathogenesis of rheumatoid arthritis.
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| ln Vitro |
In vitro, NM-3 inhibits VEGF-mediated endothelial cell proliferation with an IC50 of 1 μg/mL (approximately 3.78 μM). It inhibits angiogenesis by blocking the effects of VEGF on endothelial cells. The compound's activity is typically measured using endothelial cell proliferation assays, tube formation assays, or migration assays in the presence of VEGF. IC50 values are determined from dose-response curves. NM-3 has also been shown to have anti-arthritic effects in vitro. The compound's mechanism involves inhibition of VEGF signaling, which is a well-established target for anti-angiogenic therapy.
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| ln Vivo |
In vivo, NM-3 is an orally active anti-angiogenic agent with low toxicity. It inhibits S180 cell-induced angiogenesis in an implanted dorsal air sac in mice when administered at doses of 1, 3, and 10 mg/kg. NM-3 has been used in clinical trials for cancer treatment. The compound is also used as a radiation modulator in vitro and in vivo. Its anti-arthritic effects have been demonstrated in animal models. The compound's oral bioavailability and low toxicity make it a promising candidate for therapeutic development. The compound's ability to inhibit angiogenesis in vivo has been well-documented.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for NM-3 involve VEGF inhibition assays using purified VEGF or VEGF receptor proteins. The compound's ability to inhibit VEGF-mediated signaling is measured by monitoring the phosphorylation of VEGF receptors or downstream signaling molecules such as ERK or AKT. IC50 values are determined from dose-response curves. Binding assays using surface plasmon resonance (SPR) or ELISA can be employed to measure the affinity of NM-3 for VEGF or its receptors. These assays confirm that NM-3 directly inhibits VEGF activity.
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| Cell Assay |
In vitro cellular assays for NM-3 are conducted in endothelial cells, such as human umbilical vein endothelial cells (HUVECs). Cells are treated with varying concentrations of NM-3 in the presence of VEGF, and cell proliferation is measured using MTT or similar assays. Tube formation assays are performed on Matrigel to assess the compound's ability to inhibit endothelial cell network formation. Migration assays using Boyden chambers or wound healing assays are employed to assess the compound's effects on endothelial cell motility. These assays confirm that NM-3 engages its target in a cellular context and produces the expected inhibition of angiogenesis.
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| Animal Protocol |
In vivo animal studies for NM-3 are conducted in mouse models of angiogenesis and cancer. In the dorsal air sac model, mice are implanted with S180 cells and treated with NM-3 at doses of 1, 3, and 10 mg/kg. Angiogenesis is assessed by measuring the number and density of blood vessels in the implanted area. In xenograft models, mice are implanted with tumor cells and treated with NM-3, and tumor growth is monitored. The compound's anti-arthritic effects are assessed in animal models of rheumatoid arthritis. These studies confirm that NM-3 is effective in vivo and provide information about its therapeutic potential.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NM-3 indicate that it has a molecular weight of 264.23 and a molecular formula of C13H12O6. The compound is orally bioavailable, enabling convenient administration for in vivo studies. It is an isocoumarin with low toxicity. For storage, the powder should be kept under appropriate conditions to maintain stability. The compound's solubility and other physicochemical properties facilitate its use in in vitro assays and formulation for in vivo administration. Its oral bioavailability supports its development as a therapeutic agent.
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| Toxicity/Toxicokinetics |
The toxicological profile of NM-3 indicates that it has low toxicity. In preclinical studies, the compound has been shown to be well-tolerated at therapeutic doses. The compound has been used in clinical trials for cancer treatment, suggesting that it has an acceptable safety profile for human use. Comprehensive toxicology studies would be required for full clinical development, including assessments of hematological, hepatic, and renal function. The compound's low toxicity and oral bioavailability make it a promising candidate for further development.
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| References | |
| Additional Infomation |
NM-3 has been used in clinical trials for cancer treatment. 2-(8-hydroxy-6-methoxy-1-oxo-1H-isochromen-3-yl)propionic acid has been reported in Streptomyces eurocidicus, and relevant data are available. Isocumarin NM-3 is an orally bioavailable anti-angiogenic isocumarin with potential antitumor activity. NM-3 inhibits vascular endothelial growth factor (VEGF) (a pro-angiogenic growth factor), thereby inhibiting endothelial cell proliferation. The drug can also induce apoptosis through mechanisms involving reactive oxygen species. (NCI04)
NM-3 (isocoumarin) is an orally bioavailable anti-angiogenic isocoumarin with potential antineoplastic activity. It inhibits VEGF with an IC50 of 1 μg/mL (approximately 3.78 μM). NM-3 has anti-arthritic and anti-angiogenic effects and has been used in clinical trials for cancer treatment. It has low toxicity and is used as a radiation modulator. NM-3 is not approved for clinical use and is available from research chemical suppliers for preclinical studies. |
| Molecular Formula |
C13H12O6
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|---|---|
| Molecular Weight |
264.23
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| Exact Mass |
264.063
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| CAS # |
181427-78-1
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| PubChem CID |
5493470
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.434g/cm3
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| Boiling Point |
542.4ºC at 760mmHg
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| Flash Point |
212.5ºC
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| Vapour Pressure |
1.35E-12mmHg at 25°C
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| Index of Refraction |
1.608
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| LogP |
1.695
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
415
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C1=CC2=CC(=CC(=C2C(=O)O1)O)OC)C(=O)O
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| InChi Key |
BPZCXUROMKDLGX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H12O6/c1-6(12(15)16)10-4-7-3-8(18-2)5-9(14)11(7)13(17)19-10/h3-6,14H,1-2H3,(H,15,16)
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| Chemical Name |
2-(8-hydroxy-6-methoxy-1-oxoisochromen-3-yl)propanoic acid
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| Synonyms |
NM-3; NM3; NM 3
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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 | 3.7846 mL | 18.9229 mL | 37.8458 mL | |
| 5 mM | 0.7569 mL | 3.7846 mL | 7.5692 mL | |
| 10 mM | 0.3785 mL | 1.8923 mL | 3.7846 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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