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Aclidinium Bromide

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Chemical Structure| 320345-99-1 同义名 : LAS 34273;LAS-W 330;Aclidinium (bromide)
CAS号 : 320345-99-1
货号 : A110489
分子式 : C26H30BrNO4S2
纯度 : 98%
分子量 : 564.555
MDL号 : MFCD09954105
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(62 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • mAChR

    M4 mAChR, Ki:0.21 nM

    M2 mAChR, Ki:0.1 nM
描述 Aclidinium bromide is a novel potent, long-acting inhaled muscarinic antagonist with a fast onset of action, a long duration of effect, and a favorable cardiovascular safety profile. Aclidinium Bromide inhibits human muscarinic AChR M1, M2, M3, M4 and M5 with Ki of 0.1 nM, 0.14 nM, 0.14 nM, 0.21 nM and 0.16 nM, respectively[3]. Aclidinium was rapidly hydrolysed into carboxylic acid and alcohol derivatives in guinea pig, rat, human and dog plasma with half-lives of 38, 11.7, 2.4 and 1.8 min, respectively. Aclidinium (1 mg/ml) produces a potent and sustained bronchoprotection (72%–88.4%) over the 120-min study period in anaesthetised guinea pigs[4]. 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[5]. The expression of Bcl-2 declined, and Bax and Caspase 3 increased in A549 cells treated with Aclidinium Bromide. Additionally, Aclidinium Bromide suppressed the PI3K/AKT signaling pathway in lung cancer A549 cells. CCK-8 showed that Aclidinium Bromide could suppress the growth of lung cancer cells A549[6].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03662711 Pulmonary Disease, Chronic Obs... 展开 >>tructive 收起 << Phase 4 Recruiting September 2020 Italy ... 展开 >> Istituti Clinici Scientifici Maugeri S.p.A - SB, Pneumologia Riabilitativa Recruiting Telese Terme, Benevento, Italy, 82037 Contact: Mauro Maniscalco       mauro.maniscalco@icsmaugeri.it    Ospedale San Giovanni di Dio, UOC Medicina Interna Not yet recruiting Crotone, Calabria, Italy, 88900 Contact: Raffaele Costa       costa.raffaele@libero.it    Ospedale "Jazzolino" ASP, UOC Medicina Interna Not yet recruiting Vibo Valentia, Calabria, Italy, 89900 Contact: Luigi Anastasio       luigi.anastasio@aliceposta.it    Ospedale civile di Battipaglia, Medicina, Servizio di Allergologia e Immunologia Clinica Not yet recruiting Battipaglia, Campania, Italy, 84091 Contact: Vincenzo Patella       pobattipaglia.allerg@aslsalerno.it    Università degli studi di Modena e Reggio Emilia, Clinica Malattie dell'apparato Respiratorio Recruiting Modena, Emilia Romagna, Italy, 41124 Contact: Enrico Clini       enrico.clini@unimore.it    Azienda Ospedaliero-universitaria di Parma, Clinica pneumologica Not yet recruiting Parma, Emilia Romagna, Italy, 43126 Contact: Alfredo Chetta       chetta@unipr.it    AUSL - IRCCS di Reggio Emilia, Pneumologia Not yet recruiting Reggio Emilia, Emilia Romagna, Italy, 42122 Contact: Nicola Facciolongo       nicolacosimo.facciolongo@ausl.re.it    UNIVERSITà DEGLI STUDI DI FERRARA, CLINICA DI MALATTIE DELL'APPARATO RESPIRATORIO Recruiting Ferrara, FE, Italy, 44100 Contact: Alberto Papi, MD    +390532210420    ppa@unife.it    Sub-Investigator: Brunilda Marku, MD          Sub-Investigator: Giacomo Forini, MD          Sub-Investigator: Marianna Padovani, MD          Università degli studi di Foggia, ospedale pneumologico D'Avanzo, unità operativa di malattie dell'apparato respiratorio Not yet recruiting Foggia, FG, Italy Contact: Maria Pia Foschino, MD    +390881617832    mfoschino@qubisoft.it    Ospedale S. Maria degli Angeli - AAS5 Friuli Occidentale, Pneumologia Not yet recruiting Pordenone, Friuli Venezia Giulia, Italy, 33100 Contact: Carlo Barbetta       carlo.barbetta@aas5.sanita.fvg.it    Policlinico Universitario Campus Biomedico di Roma, Medicina Interna e Geriatria Not yet recruiting Roma, Lazio, Italy, 00128 Contact: Raffaele Antonello Incalzi       r.antonelli@unicampus.it    Università di Roma "Tor Vergata", Dipartimento di Medicina dei Sistemi, Malattie dell'apparato respiratorio Not yet recruiting Roma, Lazio, Italy, 00133 Contact: Paola Rogliani       paola.rogliani@uniroma2.it    ASL2 Savonese, Ospedale S. Corona, Pneumologia Not yet recruiting Pietra Ligure, Liguria, Italy, 17027 Contact: Manlio Milanese       m.milanese@asl2.liguria.it    Ospedale San Paolo, Medicina 2 e cure Intermedie Not yet recruiting Savona, Liguria, Italy, 17100 Contact: Paola Gnerre       pgnerre@yahoo.it    Ospedale Figlie di San Camillo, Medicina Interna Not yet recruiting Cremona, Lombardia, Italy, 26100 Contact: Maurizio Marvisi       mmarvisi@alice.it    ASST Ovest Milanese - Ospedale civile di Legnano, Medicina interna Not yet recruiting Legnano, Lombardia, Italy, 20025 Contact: Giorgio Bonardi       giorgio.bonardi@asst-ovestmi.it    Ospedale "Carlo Poma", Struttura Complessa Pneumologia e UTIR Not yet recruiting Mantova, Lombardia, Italy, 46100 Contact: Giuseppe De Donno       giuseppe.dedonno@asst-mantova.it    Ospedale "L. Sacco" - Polo Universitario ASST Fatebenefratelli Sacco, Pneumologia Not yet recruiting Milano, Lombardia, Italy, 20157 Contact: Pierachille Santus       pierachille.santus@unimi.it    Fondazione IRCCS Policlinico San Matteo, Pneumologia Not yet recruiting Pavia, Lombardia, Italy, 27100 Contact: Angelo Corsico       corsico@unipv.it    Istituti Clinici Scientifici Fondazione Maugeri, Pneumologia Riabilitativa Not yet recruiting Pavia, Lombardia, Italy, 27100 Contact: Piero Ceriana       piero.ceriana@icsmaugeri.it    Istituti Clinici Scientifici maugeri, Pneumologia Riabilitativa Not yet recruiting Tradate, Lombardia, Italy, 21049 Contact: Antonio Spanevello       antonio.spanevello@icsmaugeri.it    Ospedali Riuniti di Ancona, Pneumologia Not yet recruiting Torrette, Marche, Italy, 60030 Contact: Stefano Gasparini       s.gasparini52@gmail.com    Ospedale F. Veneziale, Medicina Interna Not yet recruiting Isernia, Molise, Italy, 86170 Contact: Cecilia Politi       cecilia.politi@asrem.org    Università degli Studi di Palermo, Ospedale "V. Cervello" Not yet recruiting Palermo, Pa, Italy, 90146 Contact: Nicola Scichilone, MD, PHD    0916802652    n.scichilone@libero.it    Università degli studi di Padova, dipartimento di Pneunmologia Not yet recruiting Padova, PD, Italy Contact: Marina Saetta, MD    +390498213732    marina.saetta@unipd.it    Ospedale Maggiore, Medicina interna Not yet recruiting Chieri, Piemonte, Italy, 10023 Contact: Roberto Frediani       rfrediani1@alice.it    Ospedale di Ceva, Medicina interna Not yet recruiting San Bernardino, Piemonte, Italy, 12073 Contact: Carlo Lorenzo Muzzulini       carlolorenzo.muzzulini@aslcn1.it    Ospedale Civile SS. Annunziata, Medicina interna Not yet recruiting Savigliano, Piemonte, Italy, 12038 Contact: Giovanni Gulli       giovanni.gulli@aslcn1.it    Policlinico Ospedaliero di Varese - Ospedale di Circolo e Fondazione Macchi, Medicina interna Not yet recruiting Varese, Piemonte, Italy, 21100 Contact: Francesco Dentali       fdentali@libero.it    Istituti Clinici Scientifici Maugeri, Pneumologia Riabilitativa Recruiting Veruno, Piemonte, Italy, 28010 Contact: Bruno Balbi       bruno.balbi@icsmaugeri.it    Università degli studi di Pisa, Ospedale Cisanello, unità operativa di Pneumologia Not yet recruiting Pisa, PI, Italy Contact: Pierluigi Paggiaro, MD    +39050995266    ppaggiaro@qubisoft.it    Istituti Clinici Scientifici Maugeri, Pneumologia Riabilitativa Not yet recruiting Cassano Delle Murge, Puglia, Italy, 70020 Contact: Maria Aliani       maria.aliani@icsmaugeri.it    Ospedale "G. Tatarella", Medicina Interna Not yet recruiting Cerignola, Puglia, Italy, 71042 Contact: Francesco Ventrella       f.ventrella@libero.it    Azienda Ospedaliero Universitaria "Policlinico Vittorio Emanuele", Pneumologia Not yet recruiting Catania, Sicilia, Italy, 95123 Contact: Claudia Crimi       dott.claudiacrimi@gmail.com    Presidio ospedaliero Muscatello di Augusta, Medicina Interna Not yet recruiting Siracusa, Sicilia, Italy, 96100 Contact: Roberto Risicato       r.risicato@inwind.it    Azienda Ospedaliero-universitaria Careggi, Medicina per la alta complessità Assistenziale 1 Not yet recruiting Firenze, Toscana, Italy, 50134 Contact: Carlo Nozzoli       nozzolicarlo@gmail.com    Azienda Ospedaliero-universitaria Careggi, Medicina per la alta complessità Assistenziale 2 Not yet recruiting Firenze, Toscana, Italy, 50134 Contact: Francesco Corradi       francescocorradi72@gmail.com    Università degli studi di Siena, UOC Malattie respiratorie Not yet recruiting Siena, Toscana, Italy, 53100 Contact: Elena Bargagli       bargagli2@gmail.com    Ospedale di Cattinara, unità operativa di pneumologia Not yet recruiting Trieste, TS, Italy Contact: Marco Confalonieri, MD    +390403993136    marco.confalonieri@aots.sanita.fvg.it 收起 <<
NCT02165826 - Completed - -
NCT02165826 Chronic Obstructive Pulmonary ... 展开 >>Disease (COPD) 收起 << Phase 3 Completed - Slovakia ... 展开 >> Bardejov, Slovakia Spisska Nova Ves, Slovakia 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.77mL

0.35mL

0.18mL

8.86mL

1.77mL

0.89mL

17.71mL

3.54mL

1.77mL
参考文献

[1]Beier J, Mroz R,.Improvement in 24-hour bronchodilation and symptom control with aclidinium bromide versus tiotropium and placebo in symptomatic patients with COPD: post hoc analysis of a Phase IIIb study. Int J Chron Obstruct Pulmon Dis. 2017 Jun 14;12:1731-1740.

[2]Sentellas S, Ramos I,. Aclidinium bromide, a new, long-acting, inhaled muscarinic antagonist: in vitro plasma inactivation and pharmacological activity of its main metabolites. Eur J Pharm Sci. 2010 Mar 18;39(5):283-90.

[3]Gavaldà A, Miralpeix M, Ramos I, Otal R, Carreño C, Viñals M, Doménech T, Carcasona C, Reyes B, Vilella D, Gras J, Cortijo J, Morcillo E, Llenas J, Ryder H, Beleta J. Characterization of aclidinium bromide, a novel inhaled muscarinic antagonist, with long duration of action and a favorable pharmacological profile. J Pharmacol Exp Ther. 2009 Nov;331(2):740-51

[4]Sentellas S, Ramos I, Albertí J, Salvà M, Antón F, Miralpeix M, Beleta J, Gavaldà A. Aclidinium bromide, a new, long-acting, inhaled muscarinic antagonist: in vitro plasma inactivation and pharmacological activity of its main metabolites. Eur J Pharm Sci. 2010 Mar 18;39(5):283-90

[5]Milara J, Serrano A, Peiró T, Gavaldà A, Miralpeix M, Morcillo EJ, Cortijo J. Aclidinium inhibits human lung fibroblast to myofibroblast transition. Thorax. 2012 Mar;67(3):229-37

[6]Lin G, He Y, Han D, Shi D, Liu T, Gao Y, Guan W, Cheng G. Aclidinium Bromide holds promising inhibitory effects in A549 lung cancer cells potentials by regulating PI3K / AKT signaling pathway. J BUON. 2019 Mar-Apr;24(2):560-565