Aclidinium Bromide (C09-0735-269)

InformationAclidinium Bromide (LAS 34273, LAS-W 330) inhibits human muscarinicAChRM1, M2, M3, M4 and M5 withKiof 0.1 nM, 0.14 nM, 0.14 nM, 0.21 nM and 0.16 nM, respectively.TargetsM1 mAChR ; M2 mAChR ; M3 mAChR ; M5 mAChR ; M4 mAChR 0.1 nM(Ki); 0.14 nM(Ki); 0.14 nM(Ki); 0.16 nM(Ki); 0.21 nM(Ki)In vitro[3H]Aclidinium binds to a homogeneous receptor of M2 with Kd of 0.34 nM and Bmax of 3.13 pmol/mg, and binds to M3 with Kd of 0.34 nM and Bmax of 3.13 pmol/mg. Aclidinium (< 100 nM) dose-dependently inhibits carbachol-induced contractions in isolated guinea pig trachea. Aclidinium shows an onset of action with t1/2 of 6.8 min, tmax of 35.9 min in isolated guinea pig trachea. Aclidinium is hydrolysed in plasma samples from all species studied, with apparent half-lives at 37℃ of 11.7 min, 38.3 min, 1.8 min and 2.4 min in rat, guinea pig, dog and human plasma, respectively. Aclidinium (0.1 μM) inhibits carbachol and TGF-β1 induced upregulation of collagen type I and α-SMA mRNA and protein expression in human bronchial fibroblasts. Aclidinium (0.1 μM) inhibits TGF-β1 induced upregulation of ChAT expression in human bronchial fibroblasts. Aclidinium (0.1 μM) inhibits carbachol- and TGF-β1-induced increases in ERK1/2 phosphorylation and RhoA-GTP formation in human bronchial fibroblasts. Aclidinium pretreatment prevents the upregulation of M1 and M3, but not M2 downregulation induced by carbachol or TGF-β1 in human lung fibroblasts. Aclidinium (0.1 μM) dose-dependently inhibits the TGF-β1 and carbachol-induced cell proliferation of human lung fibroblasts.In vivoAclidinium shows an onset of action with IC50 (95% CI) of 140 μg/mL and tmax of 30 min in the acetylcholine-induced bronchoconstriction model in anesthetized guinea pigs. Aclidinium (500 μg/kg) induces a maximal increase in heart rate of 55% after 1 hour in conscious beagle dogs. Aclidinium (1 mg/ml) produces a potent and sustained bronchoprotection (72%–88.4%) over the 120-min study period in anaesthetised guinea pigs.Cell Research(from reference)Cell lines：Human bronchial fibroblast Concentrations：100 nM Incubation Time：48 hours. Specification: 0.99 Molecular Formula: C26H30BrNO4S2 Molecular Weight: 564.57 PubChem CID: 11519741 Isomeric SMILES: C1C[N+]2(CCC1[C@H](C2)OC(=O)C(C3=CC=CS3)(C4=CC=CS4)O)CCCOC5=CC=CC=C5.[Br-] Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/A413088-SCI_e32ba6f82e6c7769c9338037ea9b4ff5.pdf