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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
ND-322 HCl targets membrane type 1 matrix metalloproteinase (MT1-MMP/MMP14) and MMP2 (gelatinase A). MT1-MMP is a transmembrane metalloproteinase that plays a critical role in extracellular matrix remodeling, cell migration, and invasion by activating pro-MMP2 and degrading extracellular matrix components. MMP2 (gelatinase A) is a secreted metalloproteinase involved in the degradation of type IV collagen, a major component of the basement membrane. Both enzymes are implicated in tumor progression, angiogenesis, and metastasis. ND-322 HCl selectively inhibits MT1-MMP and MMP2 over other MMPs such as MMP9. This selectivity makes ND-322 a valuable tool for studying the roles of MT1-MMP and MMP2 in cancer invasion and metastasis. The compound's ability to cross the BBB also suggests potential applications in neurological diseases involving MMP dysregulation.
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| ln Vitro |
In vitro, ND-322 HCl reduces melanoma cell growth, migration, and invasion. In melanoma cell lines (e.g., B16F10, A375), treatment with ND-322 HCl inhibits cell proliferation in a dose-dependent manner, with effects observed at concentrations ranging from 0.1 to 10 μM. Cell migration and invasion are assessed using wound healing assays and Transwell invasion assays, where ND-322 HCl treatment significantly reduces the number of migrating or invading cells compared to vehicle controls. The compound's activity is attributed to inhibition of MT1-MMP and MMP2 enzymatic activity, which are required for extracellular matrix degradation and cell motility. ND-322 HCl also reduces the activation of pro-MMP2 to active MMP2, further contributing to its anti-invasive effects. These in vitro findings support the compound's potential as an anti-metastatic agent.
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| ln Vivo |
In vivo, ND-322 HCl reduces melanoma tumor growth and delays metastatic dissemination in preclinical models. In mouse models of melanoma (e.g., B16F10 syngeneic models or A375 xenografts), administration of ND-322 HCl (typically via intraperitoneal injection at doses of 10-50 mg/kg, daily or every other day) results in significant tumor growth inhibition compared to vehicle-treated controls. The compound also reduces the number of metastatic lesions in the lungs and other organs, indicating an anti-metastatic effect. ND-322 HCl's ability to cross the blood-brain barrier makes it a promising candidate for studying neurological diseases involving MMP dysregulation, such as glioblastoma or neuroinflammatory conditions. The compound is also an active metabolite of the prodrug ND-478, which may offer improved pharmacokinetic properties.
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| Enzyme Assay |
In vitro enzyme assays for ND-322 HCl involve measuring the inhibition of recombinant MT1-MMP and MMP2 enzymatic activity using fluorogenic substrates. A typical protocol: recombinant human MT1-MMP or MMP2 (0.5-1.0 nM) is incubated with varying concentrations of ND-322 HCl (0.1 nM to 10 μM) in assay buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 10 mM CaCl₂, 0.05% Brij-35) for 30 minutes at 37°C. Fluorogenic substrate (e.g., Mca-PLGL-Dpa-AR-NH₂ for MMP2, or Mca-KPLGL-Dpa-AR-NH₂ for MT1-MMP) is added to a final concentration of 10 μM. Fluorescence is monitored continuously (excitation 320 nm, emission 405 nm) for 60-120 minutes using a microplate reader. IC₅₀ values are calculated by fitting inhibition curves to a four-parameter logistic model. Positive controls include known MMP inhibitors such as batimastat or marimastat. Each concentration is tested in triplicate, and experiments are repeated at least three times.
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| Cell Assay |
In vitro cell-based assays for ND-322 HCl are performed using melanoma cell lines such as B16F10, A375, or WM164. A typical protocol: cells are seeded in 96-well plates at 5,000-10,000 cells/well and allowed to adhere overnight. Cells are treated with ND-322 HCl at concentrations ranging from 0.1 to 10 μM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. For migration assays, cells are seeded in 6-well plates, a scratch is made with a pipette tip, and cells are treated with ND-322 HCl (1-5 μM) for 24-48 hours. Wound closure is measured by microscopy at 0 and 24 hours. For invasion assays, cells are seeded in Transwell inserts coated with Matrigel, and ND-322 HCl is added to both the upper and lower chambers. After 24-48 hours, invaded cells on the lower surface are fixed, stained, and counted. MMP2 activity in conditioned media is measured by gelatin zymography. Each condition is tested in triplicate, and experiments are repeated at least three times.
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| Animal Protocol |
In vivo animal studies for ND-322 HCl are conducted in mouse models of melanoma. A typical protocol: C57BL/6 mice (for B16F10 syngeneic model) or immunocompromised mice (for A375 xenograft) are inoculated subcutaneously with 1-5 × 10⁶ melanoma cells. When tumors reach 50-100 mm³, mice are randomized to receive ND-322 HCl (10-50 mg/kg, intraperitoneal) or vehicle (e.g., DMSO/saline) daily or every other day for 2-4 weeks. Tumor volumes are measured with calipers every 2-3 days, and body weight is monitored for toxicity. For metastasis studies, B16F10 cells are injected intravenously via the tail vein, and ND-322 HCl is administered daily. After 14-21 days, lungs are harvested, and metastatic colonies are counted. At study termination, tumors and organs are harvested for histopathological examination and biomarker analysis (e.g., MMP2 expression by IHC or zymography).
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of ND-322 HCl have been partially characterized. The compound is water-soluble as the hydrochloride salt and achieves a solubility of 45 mg/mL in DMSO. ND-322 is an active metabolite of the prodrug ND-478, which undergoes hydrolysis to generate ND-322 and further metabolizes into ND-364, a more potent acetylated derivative. Both ND-322 and ND-364 cross the blood-brain barrier (BBB), making them promising candidates for neurological diseases involving MMP-9 dysregulation. The compound's plasma half-life, volume of distribution, and oral bioavailability have not been fully characterized in published studies. The compound is stable as a solid powder at -20°C for long-term storage. Further pharmacokinetic studies would be needed to fully characterize its ADME properties.
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| Toxicity/Toxicokinetics |
Toxicological data for ND-322 HCl are limited to observations from in vivo efficacy studies. At the doses used in preclinical studies (10-50 mg/kg, IP), ND-322 HCl is generally well-tolerated, with no significant effects on body weight or general health reported. The compound has not undergone formal toxicology testing for regulatory purposes. Standard laboratory safety precautions should be followed when handling ND-322 HCl: use of personal protective equipment (gloves, safety goggles, lab coat) and handling in a well-ventilated fume hood. The compound should be stored at -20°C for long-term stability and at 4°C for short-term storage. No genotoxicity, carcinogenicity, or reproductive toxicity data are available. Researchers should consult the safety data sheet (SDS) before handling. The compound is for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
Additional information for ND-322 HCl: The compound has a CAS number of 1333379-23-9. Its molecular formula is C₁₅H₁₆ClNO₃S₂ and molecular weight is 357.88 g/mol. The IUPAC name is 4-(4-((thiiran-2-ylmethyl)sulfonyl)phenoxy)aniline hydrochloride. Purity is typically >98%. The compound is a selective inhibitor of MT1-MMP/MMP14 and MMP2. It reduces melanoma tumor growth and delays metastatic dissemination. ND-322 is an active metabolite of the prodrug ND-478. Both ND-322 and ND-364 cross the BBB. This product is for research use only and is not approved for clinical or diagnostic applications. No FDA approvals or investigational new drug applications exist.
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| Exact Mass |
357.026
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|---|---|
| CAS # |
1333379-23-9
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| PubChem CID |
54757100
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
22
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| Complexity |
432
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C(S1)CS(=O)(=O)C2=CC=C(C=C2)OC3=CC=C(C=C3)N.Cl
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| InChi Key |
FOCZQHBXIUOIJR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H15NO3S2.ClH/c16-11-1-3-12(4-2-11)19-13-5-7-15(8-6-13)21(17,18)10-14-9-20-14;/h1-8,14H,9-10,16H2;1H
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| Chemical Name |
4-[4-(thiiran-2-ylmethylsulfonyl)phenoxy]aniline;hydrochloride
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| Synonyms |
ND322 HCl; ND 322 HCl; ND-322 HCl
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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.) |
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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