COPD (chronic obstructive pulmonary disease) is a group of lung diseases that make it hard to breathe and get worse over time.
Normally, the airways and air sacs in your lungs are elastic or stretchy. When you breathe in, the airways bring air to the air sacs. The air sacs fill up with air, like a small balloon. When you breathe out, the air sacs deflate, and the air goes out. If you have COPD, less air flows in and out of your airways because of one or more problems:
~The airways and air sacs in your lungs become less elastic
~The walls between many of the air sacs are destroyed
~The walls of the airways become thick and inflamed
~The airways make more mucus than usual and can become clogged
COPD includes two main types:
1.Emphysema affects the air sacs in your lungs, as well as the walls between them. They become damaged and are less elastic.
2.Chronic bronchitis, in which the lining of your airways is constantly irritated and inflamed. This causes the lining to swell and make mucus.
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Freselestat is a potent, selective and orally active human neutrophil elastase (HNE) inhibitor with Ki of 12 nM; dispalys >100-fold selectivity over a panel of related proteases including trypsin, pancreatic elastase, collagenase and murine macrophage elastase; attenuates HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count, inhibits acute lung injury induced by HNE in rats.
GSK-2269557 is a highly potent and selective inhibitor of PI3Kδ (pKi=9.9); displays >1000 fold selectivity versus other PI3K isoforms; inhibits both IFNγ and IL-2 production in a concentration-dependent manner, with pIC50 values of 8.2 and 8.1, respectively, in a human lung parenchyma assay; shows activity in rat acute OVA model of Th2-driven lung inflammation (ED50=67ug/kg).
Olodaterol hydrochloride (BI1744 CL) is a potent, selective long-acting β2 adrenoceptor agonist with EC50 of 1.4 nM for hβ2; shows >250 fold selectivity over hβ1; exerts a bronchodilatory efficacy over 24 h in dogs and guinea pigs in the absence of systemic pharmacodynamic effects.
Umeclidinium bromide (GSK 573719A) is potent, long-acting, inhaled antagonist of mAChRs with Ki of 0.05-0.16 nM for human M1-M5 mAChRs; demonstrates picomolar potency (-log pA2=23.9 pM) in an acetylcholine-mediated Ca(2+) mobilization assay in CHO cells transfected M3 mAChRs; dose dependently blocks Ach-induced bronchoconstriction with long duration of action in mice model of pulmonary diseases.
BAY 85-8501 (BAY85-8501) is a potent, selective human neutrophil elastase (HNE) inhibitor with IC50 of 65 pM; displays no significant inhibition toward 21 related serine proteases (>30 uM); demonstrates completely prevented the development of lung injury and subsequent inflammation in vivo.
AQX 1125 is a sepecific, orally bioavailable SHIP1 activator with no effect on functional androgen, oestrogen, oestrogen-related receptor α, glucocorticoid, mineralocorticoid and progesterone receptor at 30 uM; inhibits the pAkt (S473) in MOLT-4 cells, and inhibits cytokine release in mixed splenocytes; significantly decreases β-hexosaminidase release in mouse BMMCs; inhibits chemotaxis in human mononuclear cells (EC50=0.26 uM); suppresses leukocyte accumulation and inflammatory mediator release in rodent models of pulmonary inflammation and allergy.
AQX 1125 acetate is a sepecific, orally bioavailable SHIP1 activator with no effect on functional androgen, oestrogen, oestrogen-related receptor α, glucocorticoid, mineralocorticoid and progesterone receptor at 30 uM; inhibits the pAkt (S473) in MOLT-4 cells, and inhibits cytokine release in mixed splenocytes; significantly decreases β-hexosaminidase release in mouse BMMCs; inhibits chemotaxis in human mononuclear cells (EC50=0.26 uM); suppresses leukocyte accumulation and inflammatory mediator release in rodent models of pulmonary inflammation and allergy.
TG100-115 is a potent, selective PI3Kγ/δ with IC50 of 83/235 nM, respectively; shows no significant inhibitory activity against pI3Kα and β, and a broad panel of kinases (IC50>1 uM); potently inhibits edema and inflammation in response to multiple mediators known to participate in myocardial infarction, such as VEGF and platelet-activating factor, without effect on endothelial cell mitogenesis; provides potent cardioprotection, reduces infarct development and preserves myocardial function in animal MI models.
AZD-7624(AZD7624) is a potent, selective, inhaled p38α MAPK inhibitor with pIC50 of 10.0, displays 15-fold selectivity for p38α over p38β MAPK and >10,000-fold selectivity over p38γ and p38δ MAPK; inhibits LPS-induced TNF-α and IL-6 release in human alveolar macrophages pIC50 of 9.2 and 8.8, respectively; shows potential for prevention of exacerbations in COPD.
JNJ-49095397 (RV568;RV-568;JNJ49095397) is a specific narrow-spectrum kinase inhibitor that inhibits a selected set of kinases involved in COPD inflammation with IC50 of 5, 40 and 52 nM for p38α, p38γ and HCK, respectively; shows potent anti-inflammatory effects in monocytes and macrophages, demonstrates synergistic interaction in poly I:C-stimulated BEAS-2B cells and in the cigarette smoke model combined with corticosteroid.
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