| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
MMP-1 (~1900 nM), MMP-2 (0.81 nM), MMP-3 (120 nM), MMP-8 (10.8 nM), MMP-9 (18 nM), MMP-13 (0.56 nM), ADAM10/TACE (1-2 nM).
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|---|---|
| ln Vitro |
XL-784 is a highly powerful, low molecular weight (1,122 g/mol) MMP inhibitor with very poor water solubility (20 μg/mL). XL-784 potently inhibits MMP-2, MMP-13 and ADAM10 [TNF-alpha converting enzyme (TACE)] activities in vitro with IC50 values in the range of 1-2 nM. XL-784 also suppresses MMP-9 (IC50 ~20 nM) activity and ADAM17 (IC50 ~70 nM) also known as TACE. However, its inhibitory effectiveness against MMP-1 is low (IC50 ~2,000 nM)[1].
XL-784 potently inhibits MMP-2, MMP-13, and ADAM10/TACE activities with IC50 values in the range of 1-2 nM. It shows selectivity for these targets over MMP-1 (IC50 ~1900 nM) and MMP-3 (IC50 120 nM). |
| ln Vivo |
Every mouse responded to therapy in a similar way. Aneurysms formed in all control animals; the average percentage of ΔAD was 158.5%±4.3%. The doxycycline therapy and all XL-784 dosages effectively prevented aortic dilatation. Reduced aortic dilatation at harvest was directly correlated with XL-784 dose-response ratios of 50 mg/kg 140.4% ±3.2%; 125 mg/kg 129.3% ±5.1%; 250 mg/kg 119.2% ±3.5%; and 250 mg/kg 119.2% ±3.5%). When compared to the control, all Ps<0.01. At higher doses (375 mg/kg 88.6% ± 4.4%; 500 mg/kg 76.0% ± 3.5%), this pattern persisted. When it came to preventing maximal aortic dilatation following elastase infusion, the two highest dosages of XL-784 that were tested out performed effectively (112.2% ± 2.0%, P < 0.05) [2].
XL-784 regulates extracellular matrix remodeling through inhibition of MMPs. In vivo, it is expected to show efficacy in models of cancer metastasis, arthritis, and wound healing by modulating matrix degradation and inflammatory cytokine processing. |
| Enzyme Assay |
MMP enzyme activity assays are performed using purified recombinant MMPs and fluorogenic peptide substrates. The enzyme is incubated with the substrate and the compound. Fluorescence is measured to quantify substrate cleavage. IC50 values are determined from concentration-response curves.
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| Cell Assay |
Cells expressing MMPs (e.g., cancer cell lines or fibroblasts) are treated with XL-784. MMP activity in the culture supernatant is measured using zymography or fluorogenic substrate assays. Cell migration and invasion assays (Boyden chamber) assess the functional effects of MMP inhibition.
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| Animal Protocol |
Animal models of cancer metastasis, arthritis, or wound healing are used to assess the in vivo efficacy of XL-784. Tumor growth, metastasis, joint inflammation, or wound closure are measured following compound administration.
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| ADME/Pharmacokinetics |
XL-784 has very poor aqueous solubility (20 ug/mL), which may limit oral bioavailability. The compound is likely administered parenterally for in vivo studies. Metabolism is expected to be mediated by CYP450 enzymes. Half-life in rodents is estimated to be 2-4 hours.
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| Toxicity/Toxicokinetics |
No specific toxicity data reported for XL-784. MMP inhibitors have been associated with musculoskeletal side effects (musculoskeletal syndrome) in clinical trials. The selectivity profile of XL-784 may reduce the risk of these side effects.
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| References | |
| Additional Infomation |
XL-784 is a research tool for studying the role of MMPs and ADAM10/TACE in extracellular matrix remodeling, inflammation, and cancer. It has not been approved for clinical use. The compound's mechanism involves inhibition of zinc-dependent metalloproteinases, preventing the degradation of extracellular matrix components and the processing of inflammatory cytokines such as TNF-alpha.
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| Molecular Formula |
C21H22CLF2N3O8S
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|---|---|
| Molecular Weight |
549.929490566254
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| Exact Mass |
549.078
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| CAS # |
1224964-36-6
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| Related CAS # |
XL-784 free base;1356992-21-6
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| PubChem CID |
74439626
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| Appearance |
White to off-white solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
36
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| Complexity |
847
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1)OC1=C(C=C(C=C1F)S(N1CCN(C(=O)OCCOC)CC1C(NO)=O)(=O)=O)F
|
| InChi Key |
PRIJGYZAOBNIPH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H22ClF2N3O8S/c1-33-8-9-34-21(29)26-6-7-27(18(12-26)20(28)25-30)36(31,32)15-10-16(23)19(17(24)11-15)35-14-4-2-13(22)3-5-14/h2-5,10-11,18,30H,6-9,12H2,1H3,(H,25,28)
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| Chemical Name |
2-methoxyethyl 4-[4-(4-chlorophenoxy)-3,5-difluorophenyl]sulfonyl-3-(hydroxycarbamoyl)piperazine-1-carboxylate
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO : ≥ 110 mg/mL (~200.39 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (5.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (5.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (5.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8184 mL | 9.0921 mL | 18.1841 mL | |
| 5 mM | 0.3637 mL | 1.8184 mL | 3.6368 mL | |
| 10 mM | 0.1818 mL | 0.9092 mL | 1.8184 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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