| Size | Price | Stock | Qty |
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| 10mg |
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Purity: ≥98%
GW311616 (GW-311616), the free base form of GW311616A, is a novel, potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase(HNE) with IC50 of 22 nM.
| 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].
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| 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].
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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. |
| 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%. |
| References |
[1]. Ohbayashi H,et al. Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80.
[2]. Jiang KL, et al. Neutrophil elastase and its therapeutic effect on leukemia cells. Mol Med Rep. 2015 Sep;12(3):4165-4172. [3]. Macdonald SJ, et al. The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase--GW311616A a development candidate. Bioorg Med Chem Lett. 2001 Apr 9;11(7):895-8. |
| Molecular Formula |
C19H31N3O4S
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|---|---|
| Molecular Weight |
397.53214
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| CAS # |
198062-54-3
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| Related CAS # |
GW311616 hydrochloride;197890-44-1
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| SMILES |
O=C1[C@@H](C(C)C)[C@@](N(C(/C=C/CN2CCCCC2)=O)CC3)([H])[C@]3([H])N1S(=O)(C)=O
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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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| 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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