| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GW-311616 targets human neutrophil elastase (HNE), a serine protease released by activated neutrophils that can degrade extracellular matrix proteins and contribute to tissue damage in inflammatory diseases. The compound is a selective and potent inhibitor with an IC50 of 22 nM and a Ki of 0.31 nM.
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| ln Vitro |
NE activity in U937 and K562 cell lines is dramatically inhibited by GW-311616 (150 μM; 48 hours) [2]. Leukemia cells are treated with GW-311616 (20-320 μM; 48 hours; U937 cells) to cause apoptosis and limit cell growth [2]. When U937 cells are treated with GW-311616 (150 μM), Bax protein expression increases while Bcl-2 expression decreases [2].
In vitro, GW-311616 (150 μM) increases Bax protein expression and decreases Bcl-2 expression in U937 cells. It markedly suppresses neutrophil elastase activity in U937 and K562 cell lines at 150 μM. Treatment with 20-320 μM for 48 hours inhibits proliferation and induces apoptosis in leukemia cells. The compound shows potent enzyme inhibition in cell-free assays. |
| ln Vivo |
In dogs, GW-311616 (2 mg/kg; oral) quickly removes circulating neutrophil elastase (NE) with >90% inhibition sustained over a 4-day period. Oral GW-311616 neutrophil infiltration in the bone marrow is not responsible for this sustained impact. GW-311616's intermediate terminal elimination half-lives (t1/2) in dogs (2 mg/kg, po) and rats (2 mg/kg, po) are 1.1 and 1.5 hours, respectively [3].
In vivo, GW-311616 (2 mg/kg; oral) rapidly abolishes circulating neutrophil elastase in dogs, with >90% inhibition sustained over 4 days. This prolonged effect is not due to penetration of neutrophils in bone marrow by orally administered GW-311616. The compound demonstrates moderate terminal elimination half-lives of 1.1 hours in dogs and 1.5 hours in rats. |
| Enzyme Assay |
For enzyme inhibition assays, human neutrophil elastase is incubated with a fluorogenic or chromogenic substrate (e.g., MeOSuc-AAPV-pNA) and varying concentrations of GW-311616. The cleavage of the substrate is monitored spectrophotometrically or fluorometrically, and the IC50 and Ki values are calculated from the inhibition curves.
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| Cell Assay |
Cell viability assay [2]
Cell Types: U937 and K562 Cell Tested Concentrations: 150 μM Incubation Duration: 48 hrs (hours) Experimental Results: NE activity was Dramatically inhibited. Apoptosis analysis [2] Cell Types: U937 Cell Tested Concentrations: 20 μM, 40 μM, 80 μM, 160 μM, 320 μM Incubation Duration: 48 hrs (hours) Experimental Results: Increased cell apoptosis rate. Western Blot Analysis [2] Cell Types: U937 cells Tested Concentrations: 150 μM Incubation Duration: 48 hrs (hours) Experimental Results: The expression level of Bax protein increased, and the expression level of Bcl-2 protein diminished. Cellular assays are performed using U937 and K562 cell lines. Cells are treated with GW-311616 at concentrations ranging from 20-320 μM for 48 hours. Cell proliferation is assessed by MTT or cell counting, and apoptosis is evaluated by flow cytometry using Annexin V/PI staining. Neutrophil elastase activity in cell lysates is measured using specific substrates. |
| Animal Protocol |
Animal/Disease Models: Dog (9 months old) [3]
Doses: 0.22 mg/kg, 0.66 mg/kg, and 2 mg/kg (pharmacokinetic/PK/PK study) Route of Administration: Oral Experimental Results: At 0.22 mg/kg, > Inhibition of elastase was achieved 6 hrs (hrs (hours)) after 50% administration, and activity returned to control values. A single oral dose of 2 mg/kg can rapidly eliminate circulating enzyme activity, and the inhibitory effect can be maintained for more than 4 days, with an inhibition rate greater than 90%. In vivo studies are conducted in dogs and rats. Animals receive oral administration of GW-311616 at 2 mg/kg, and blood samples are collected at various time points. Circulating neutrophil elastase activity is measured in plasma using specific substrates. Pharmacokinetic parameters including half-life are calculated from plasma concentration-time profiles. |
| ADME/Pharmacokinetics |
GW-311616 (molecular weight 397.53) is orally bioavailable with good pharmacokinetic properties. It is soluble in DMSO (44 mg/mL, 110.68 mM). The compound shows moderate terminal elimination half-lives of 1.1 hours in dogs and 1.5 hours in rats following oral administration at 2 mg/kg.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies have evaluated GW-311616 in animal models. As a neutrophil elastase inhibitor, the compound's safety profile is related to its immunomodulatory effects. No significant toxicity has been reported at therapeutic doses. The compound's long duration of action suggests a favorable dosing schedule.
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| References |
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| Additional Infomation |
GW-311616 is a potent and selective human neutrophil elastase inhibitor developed for inflammatory conditions. Its mechanism involves inhibition of HNE enzymatic activity, preventing degradation of extracellular matrix proteins and reducing tissue damage in neutrophil-mediated inflammatory diseases. The compound's oral bioavailability and long duration of action make it a promising candidate for therapeutic development.
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| Molecular Formula |
C19H31N3O4S
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|---|---|
| Molecular Weight |
397.53214
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| Exact Mass |
397.203
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| CAS # |
198062-54-3
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| Related CAS # |
GW311616 hydrochloride;197890-44-1
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| PubChem CID |
9800961
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| Appearance |
Light brown to brown solid powder
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| Boiling Point |
604.3ºC at 760mmHg
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| Flash Point |
319.3ºC
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| Vapour Pressure |
7.06E-15mmHg at 25°C
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| LogP |
2.768
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
707
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC(C)[C@H]1[C@H]2[C@@H](CCN2C(=O)/C=C/CN3CCCCC3)N(C1=O)S(=O)(=O)C
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| InChi Key |
NDNKNUMSTIMSHQ-URZKGLGPSA-N
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| InChi Code |
InChI=1S/C19H31N3O4S/c1-14(2)17-18-15(22(19(17)24)27(3,25)26)9-13-21(18)16(23)8-7-12-20-10-5-4-6-11-20/h7-8,14-15,17-18H,4-6,9-13H2,1-3H3/b8-7+/t15-,17+,18-/m1/s1
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| Chemical Name |
Pyrrolo(3,2-b)pyrrol-2(1H)-one, hexahydro-3-(1-methylethyl)-1-(methylsulfonyl)-4-((2E)-1-oxo-4-(1-piperidinyl)-2-buten-1-yl)-, (3S,3aS,6aR)-
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| Synonyms |
GW311616; (+)-GW 311616; GW 311616; GW-311616; (+)-GW-311616; (+)-GW311616.
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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) |
DMSO : ~66.67 mg/mL (~167.71 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.29 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
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 (6.29 mM) 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; with ultrasonication. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5155 mL | 12.5777 mL | 25.1553 mL | |
| 5 mM | 0.5031 mL | 2.5155 mL | 5.0311 mL | |
| 10 mM | 0.2516 mL | 1.2578 mL | 2.5155 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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