| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
VD2173 targets matriptase (also known as ST14) and hepsin (HPN), two type II transmembrane serine proteases that proteolytically activate the hepatocyte growth factor (HGF) precursor. HGF activation triggers signaling through the MET receptor tyrosine kinase, promoting tumor progression, invasion, and resistance to receptor tyrosine kinase inhibitors.
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| ln Vitro |
The inhibitory activity of VD2173 epimer‑1 may differ from that of the single enantiomer(s). In general, macrocyclic serine protease inhibitors are evaluated in fluorogenic substrate assays using recombinant human matriptase or hepsin. The concentration needed to inhibit 50% of enzyme activity is typically in the low nanomolar range for the most active stereoisomer, but the racemate may show reduced activity.
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| ln Vivo |
In vivo efficacy studies have not been reported specifically for VD2173 epimer‑1. The non‑racemic VD2173 has been shown to block lung cancer progression in mouse xenograft models, where it overcomes resistance to receptor tyrosine kinase inhibitors and suppresses tumor growth. The epimer‑1 formulation might serve as a control or as a pre‑purification mixture.
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| Enzyme Assay |
The enzyme assay is performed in 96‑well plates using recombinant human matriptase (1 nM) or hepsin (5 nM) and a fluorogenic peptide substrate (e.g., Boc‑Gln‑Ala‑Arg‑AMC, 50 uM) in assay buffer (50 mM Tris‑HCl, pH 8.5, 10 mM CaCl2, 0.01% Triton X‑100). VD2173 epimer‑1 is added at 0.1‑1000 nM. Fluorescence (excitation 360 nm, emission 460 nm) is read continuously for 30‑60 minutes. The initial velocity is calculated, and IC₅0 values are determined by non‑linear regression.
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| Cell Assay |
Cell‑based assays are performed using human lung cancer cell lines (e.g., A549, H1975, or HCC827). Cells are seeded in 96‑well plates and treated with VD2173 epimer‑1 (0.01‑100 uM) for 48‑72 hours. Viability is measured with an MTT or CellTiter‑Glo assay. Alternatively, HGF‑induced MET phosphorylation can be measured by Western blotting or ELISA in cells pre‑incubated with the inhibitor.
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| Animal Protocol |
Mouse xenograft models are established by subcutaneous injection of lung cancer cells into immunocompromised mice (e.g., nu/nu mice). After tumors reach 100‑150 mm3, VD2173 (25‑50 mg/kg) is administered intraperitoneally daily for 2‑3 weeks. Tumor volumes are measured with calipers every 2‑3 days. At the end of the study, tumors are excised and analyzed for matriptase/hepsin activity and MET phosphorylation.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of VD2173 epimer‑1 are expected to be similar to those of the non‑racemic VD2173, given the same molecular weight (672 g/mol) and basic peptide structure. The compound is likely to have moderate oral bioavailability (20‑40%) and a short elimination half‑life (1‑4 hours) due to protease‑mediated degradation. The epimeric form may have different plasma protein binding and clearance.
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| Toxicity/Toxicokinetics |
Animal toxicity studies have not been published specifically for VD2173 or its epimer‑1. As a serine protease inhibitor with a peptide scaffold, the compound is expected to be relatively safe at low doses but could cause off‑target gastrointestinal or coagulation disturbances at high doses, given the essential roles of some serine proteases in digestion and blood clotting.
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| References |
[1]. Damalanka VC, et, al. Macrocyclic Inhibitors of HGF-Activating Serine Proteases Overcome Resistance to Receptor Tyrosine Kinase Inhibitors and Block Lung Cancer Progression. J Med Chem. 2021 Dec 23;64(24):18158-18174.
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| Additional Infomation |
VD2173 was developed as a chemical probe to overcome resistance to receptor tyrosine kinase inhibitors in lung cancer. By inhibiting matriptase and hepsin, it prevents the activation of HGF and subsequent MET signaling, a major resistance mechanism to EGFR inhibitors. VD2173 epimer‑1 serves as a research tool for exploring stereochemical requirements for serine protease inhibition and for controlling non‑stereospecific binding effects. The compound is still in the preclinical research stage.
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| Molecular Formula |
C31H45N9O6S
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| Related CAS # |
VD2173;2574389-19-6
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| Appearance |
Off-white to light yellow solid powder
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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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