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GW311616 HCl, the hydrochloride salt of GW 311616 (GW-311616), is an orally bioavailable and long acting inhibitor of human neutrophil elastase(HNE) with IC50 of 22 nM.
| ln Vitro |
GW-311616 (150 μM; 48 hours) strongly suppresses NE activity in U937 and K562 cell lines [2]. Treatment with GW311616A (20-320 μM; 48 hours; U937 cells) reduces the growth of leukemia cells and promotes apoptosis [2]. Treatment with GW-311616 (150 μM; U937 cells) can enhance the protein expression level of Bax and diminish the expression of Bcl-2 [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 last for more than 4 days, and the inhibition rate can reach more than 90%. |
| References |
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| Additional Infomation |
See also: GW-311616 (annotation moved to).
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| Molecular Formula |
C₁₉H₃₂CLN₃O₄S
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|---|---|
| Molecular Weight |
433.99
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| Exact Mass |
433.18
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| CAS # |
197890-44-1
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| Related CAS # |
GW311616;198062-54-3
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| PubChem CID |
9889108
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| Appearance |
White to yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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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.Cl
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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 |
(3S,3aS,6aR)-hexahydro-3-(1-methylethyl)-1-(methylsulfonyl)-4-[(2E)-1-oxo-4-(1-piperidinyl)-2-buten-1-yl]-pyrrolo[3,2-b]pyrrol-2(1H)-one, monohydrochloride
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| Synonyms |
GW311616AGW311616AGW-311616A GW 311616A
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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 : ~100 mg/mL (~230.42 mM)
H2O : ~100 mg/mL (~230.42 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.76 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 (5.76 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 (5.76 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 | 2.3042 mL | 11.5210 mL | 23.0420 mL | |
| 5 mM | 0.4608 mL | 2.3042 mL | 4.6084 mL | |
| 10 mM | 0.2304 mL | 1.1521 mL | 2.3042 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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