85 CHF CHF 85.00
AG-CR1-3632-M0011 mgCHF 85.00
AG-CR1-3632-M0055 mgCHF 250.00
AG-CR1-3632-M02525 mgCHF 780.00
|Synonyms||GW311616 . hydrochloride; (3S,3aS,6aR)-3-Isopropyl-1-(methylsulfonyl)-4-((E)-4-(piperidin-1-yl)but-2-enoyl) hexahydropyrrolo [3,2-b]pyrrol-2(1H)-one|
C19H31N3O4S . HCl
|MW||397.5 . 36.5|
198062-54-3 (free base)
|Purity Chemicals||≥98% (HPLC)|
Soluble in DMSO or distilled water.
Note: To solubilize use distilled water (no buffer). In biological buffers pH>6.5 the product precipitates.
|Identity||Determined by 1H-NMR.|
|Shipping and Handling|
|Short Term Storage||+4°C|
|Long Term Storage||-20°C|
|Handling Advice||Keep cool and dry.|
|Use/Stability||Stable for at least 2 years after receipt when stored at -20°C.|
|Product Specification Sheet|
- Potent, selective intracellular neutrophil elastase (NE, α-1-proteinase) inhibitor (by covalently binding to NE).
- Inhibits human neutrophil elastase (HNE) and is selective over other human serine proteases with IC50 values of 22nM for HNE, >100μM for trypsin, cathepsin G and plasmin, >3μM for chymotrypsin and tissue plasminogen activator.
- Specific β-cell proliferation promoter. Similar to SerpinB1, which functions through its inhibiting activity of several proteases including neutrophil elastase, cathepsin G and proteinase-3.
- Reverses insulin resistance and body weight gain in HFD-fed mice, suggesting that the SerpinA1-NE system regulates AMPK signaling, fatty acid oxidation (FAO) and energy expenditure. The imbalance between SerpinA1 (α1-antitrypsin; A1AT) and neutrophil elastase NE contributes to the development of obesity and related inflammation, insulin resistance and liver steatosis.
- Shown to inhibit tumor cell growth and proliferation and induce apoptosis in leukemia cell lines.
- The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase-GW311616A a development candidate: S.J. Macdonald, et al.; Bioorg. Med. Chem. Lett. 11, 895 (2001)
- Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure: V. Mansuy-Aubert, et al.; Cell Metab. 17, 534 (2013)
- Neutrophil elastase and its therapeutic effect on leukemia cells: K.L. Jiang, et al.; Mol. Med. Rep. 12, 4165 (2015)
- SerpinB1 Promotes Pancreatic β Cell Proliferation: A. El Ouaamari, et al.; Cell Metab. 23, 194 (2016)
- Immature low-density neutrophils exhibit metabolic flexibility that facilitates breast cancer liver metastasis: B.E Hsu, et al.; Cell Rep. 27, 3902 (2019)