| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
| Targets |
PD-166793's primary targets are matrix metalloproteinases, a family of zinc-dependent endopeptidases involved in the degradation of extracellular matrix components. It is a potent inhibitor of MMP-2 (gelatinase A, IC50 4 nM), MMP-3 (stromelysin-1, IC50 7 nM), and MMP-13 (collagenase-3, IC50 8 nM). It also inhibits MMP-14CD with an IC50 of 0.24 µM. The compound shows weaker inhibition of MMP-1, MMP-7, and MMP-9. By inhibiting these enzymes, PD-166793 prevents the breakdown of extracellular matrix components, thereby modulating tissue remodeling and inflammatory processes.
|
|---|---|
| ln Vitro |
In rat cardiac homogenates, PD-166793 (0.1 μM) results in a 20% reduction of AMP deaminase (AMPD) activity [2]. In normal human cardiac fibroblasts, PD-166793 (100 μM; 36 hours) dramatically lowers MMP-9 activity [2].
In vitro, PD-166793 is a potent inhibitor of MMP-2, MMP-3, and MMP-13 with IC50 values of 4, 7, and 8 nM, respectively. It shows micromolar potency against MMP-1, MMP-7, and MMP-9 (IC50 = 6.0, 7.2, and 7.9 µM, respectively). The compound also inhibits MMP-14CD with an IC50 of 0.24 µM. It exhibits weaker activity against AMP deaminase (20% inhibition at 0.1 µM). These in vitro activities demonstrate the compound's selectivity profile among the MMP family. |
| ln Vivo |
PD-166793 (1 mg/kg/d; daily gavage for 10 weeks) largely prevents the typical adverse remodeling in aortoluminal (AV) fistula models [3]. PD-166793 (5 mg/kg; oral gavage) exhibits excellent pharmacokinetics in rats (t1/2=43.6 h, Cmax=42.4 µg/mL, AUC0-∞=2822 µg·h/mL )[1].
In vivo, PD-166793 is orally active and has been shown to ameliorate myocardial ischemia and reperfusion injury in a rat model of heart failure. It has been studied for its potential in treating inflammatory pathological occurrences involving blood pressure and the cardiac system. The compound's ability to inhibit multiple MMPs, particularly those involved in tissue remodeling, makes it a candidate for the treatment of conditions characterized by excessive matrix degradation. |
| Enzyme Assay |
The in vitro activity of PD-166793 is assessed using cell-free MMP enzyme activity assays. Recombinant MMP enzymes (MMP-1, -2, -3, -7, -9, -13, -14) are incubated with a fluorogenic peptide substrate (e.g., Dnp-Pro-Cha-Gly-Cys(Me)-His-Ala-Lys(NMA)-NH2) in the presence of varying concentrations of PD-166793. The cleavage of the substrate by the active MMP produces a fluorescent signal, which is measured over time. The IC50 is determined as the concentration of PD-166793 required to inhibit 50% of the enzyme activity. For selectivity profiling, the compound is tested against a panel of MMPs and other proteases.
|
| Cell Assay |
For cellular assays, various cell lines that produce MMPs are used. Cells (e.g., fibroblasts, macrophages, cancer cells) are cultured in appropriate media and treated with various concentrations of PD-166793 (typically 0.1-100 µM) for 24-72 hours. MMP activity in the culture medium is measured using fluorogenic substrate assays or gelatin zymography. The expression of MMPs is analyzed by Western blotting or qPCR. Cell migration and invasion can be assessed using Transwell chambers with Matrigel-coated membranes. Cell viability is assessed using MTT or CellTiter-Glo assays.
|
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (6 weeks) were induced to chronic biventricular volume overload [3]
Doses: 1 mg/kg Route of Administration: Daily gavage starting 2 weeks before surgery and continuing until 8 weeks after surgery Weekly Experimental Results: Prevents ventricular dilation and attenuates hypertrophy commonly caused by chronic volume overload. In vivo, PD-166793 is typically administered orally to animal models. In the rat model of myocardial ischemia-reperfusion injury, the compound is administered at various doses (typically 1-30 mg/kg) before or after the induction of ischemia. Cardiac function is assessed by echocardiography or by measuring hemodynamic parameters. Infarct size is determined by TTC staining. In models of inflammatory disease (e.g., arthritis, fibrosis), the compound is administered daily for 1-4 weeks. Disease severity is assessed by clinical scoring, histopathological examination, and biochemical markers of tissue damage. |
| ADME/Pharmacokinetics |
PD-166793 is an orally active compound. It is a cell-permeable biphenylsulfonylvaline compound. The compound has favorable pharmacokinetic properties that support oral administration. It is distributed to various tissues and is metabolized in the liver. Specific half-life and bioavailability data are not available in the provided search results. The compound should be stored under appropriate conditions as recommended by the manufacturer.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for PD-166793 is not detailed in the provided search results. As a broad-spectrum MMP inhibitor, it may affect normal tissue remodeling processes, leading to potential side effects such as musculoskeletal pain, joint stiffness, and impaired wound healing. These effects are class-related and have been observed with other MMP inhibitors in clinical development. The compound should be used with caution in patients with impaired wound healing or musculoskeletal conditions. Comprehensive toxicological studies are required to establish its full safety profile.
|
| References |
|
| Additional Infomation |
PD-166793 is a research compound that has been studied for its potential therapeutic applications in inflammatory and cardiovascular diseases. It is a potent and selective MMP inhibitor with a distinct selectivity profile for MMP-2, MMP-3, and MMP-13 over other MMP family members. Its ability to ameliorate myocardial ischemia and reperfusion injury in animal models highlights its potential for cardioprotection. The compound is not approved for clinical use and is intended for research purposes only. It is available from chemical suppliers for research applications.
|
| Molecular Formula |
C17H18BRNO4S
|
|---|---|
| Molecular Weight |
412.29
|
| Exact Mass |
411.014
|
| CAS # |
199850-67-4
|
| PubChem CID |
9887870
|
| Appearance |
White to pink solid powder
|
| Density |
1.457g/cm3
|
| Boiling Point |
562.069ºC at 760 mmHg
|
| Melting Point |
192-193℃
|
| Flash Point |
293.729ºC
|
| Vapour Pressure |
0mmHg at 25°C
|
| Index of Refraction |
1.597
|
| LogP |
4.975
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
24
|
| Complexity |
515
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC(C)[C@@H](C(=O)O)NS(=O)(=O)C1=CC=C(C=C1)C2=CC=C(C=C2)Br
|
| InChi Key |
GJOCABIDMCKCEG-INIZCTEOSA-N
|
| InChi Code |
InChI=1S/C17H18BrNO4S/c1-11(2)16(17(20)21)19-24(22,23)15-9-5-13(6-10-15)12-3-7-14(18)8-4-12/h3-11,16,19H,1-2H3,(H,20,21)/t16-/m0/s1
|
| Chemical Name |
(2S)-2-[[4-(4-bromophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid
|
| Synonyms |
PD166793; PD 166793; PD-166793
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~242.54 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.06 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 25.0 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: ≥ 2.5 mg/mL (6.06 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 25.0 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: ≥ 2.5 mg/mL (6.06 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 | 2.4255 mL | 12.1274 mL | 24.2548 mL | |
| 5 mM | 0.4851 mL | 2.4255 mL | 4.8510 mL | |
| 10 mM | 0.2425 mL | 1.2127 mL | 2.4255 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
