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Crystalline forms of 2,2,2-trifluoro-N-[(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(3-methoxyphenyl)-2-propanyl]acetamide (AZD-5423).
Norman P. Norman P. Expert Opin Ther Pat. 2013 Sep;23(9):1239-45. doi: 10.1517/13543776.2013.820706. Epub 2013 Jul 19. Expert Opin Ther Pat. 2013. PMID: 23865465
A crystalline form (form B) of the novel glucocorticoid receptor agonist 2,2,2-trifluoro-N-[(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(3-methoxyphenyl …
A crystalline form (form B) of the novel glucocorticoid receptor agonist 2,2,2-trifluoro-N-[(1R,2S)-1 …
RIPK3 inhibitor-AZD5423 alleviates acute kidney injury by inhibiting necroptosis and inflammation.
Xu CH, Wang JN, Suo XG, Ji ML, He XY, Chen X, Zhu S, He Y, Xie SS, Li C, Dong ZH, Chen Y, Ni WJ, Feng XW, Liu MM, Jin J, Li Z, Meng XM. Xu CH, et al. Int Immunopharmacol. 2022 Nov;112:109262. doi: 10.1016/j.intimp.2022.109262. Epub 2022 Sep 24. Int Immunopharmacol. 2022. PMID: 36166972
Necroptosis is a form of regulated cell death that requires activation of receptor interacting protein kinase 3 (RIPK3) and its phosphorylation of the substrate MLKL. RIPK3 plays an important role in acute kidney injury, and hence developing its inhibitors is considered as …
Necroptosis is a form of regulated cell death that requires activation of receptor interacting protein kinase 3 (RIPK3) and its phosp …
Selective Nonsteroidal Glucocorticoid Receptor Modulators for the Inhaled Treatment of Pulmonary Diseases.
Hemmerling M, Nilsson S, Edman K, Eirefelt S, Russell W, Hendrickx R, Johnsson E, Kärrman Mårdh C, Berger M, Rehwinkel H, Abrahamsson A, Dahmén J, Eriksson AR, Gabos B, Henriksson K, Hossain N, Ivanova S, Jansson AH, Jensen TJ, Jerre A, Johansson H, Klingstedt T, Lepistö M, Lindsjö M, Mile I, Nikitidis G, Steele J, Tehler U, Wissler L, Hansson T. Hemmerling M, et al. J Med Chem. 2017 Oct 26;60(20):8591-8605. doi: 10.1021/acs.jmedchem.7b01215. Epub 2017 Oct 12. J Med Chem. 2017. PMID: 28937774
Further optimization of inhaled drug properties provided a second, equally potent, candidate, 15m (AZD7594), that demonstrated an improved therapeutic ratio over the benchmark inhaled corticosteroid 3 (fluticasone propionate) and prolonged the inhibition of lung edema, ind …
Further optimization of inhaled drug properties provided a second, equally potent, candidate, 15m (AZD7594), that demonstrated an improved t …
Pulmonary Dissolution of Poorly Soluble Compounds Studied in an ex Vivo Rat Lung Model.
Eriksson J, Thörn H, Sjögren E, Holmstén L, Rubin K, Lennernäs H. Eriksson J, et al. Mol Pharm. 2019 Jul 1;16(7):3053-3064. doi: 10.1021/acs.molpharmaceut.9b00289. Epub 2019 Jun 11. Mol Pharm. 2019. PMID: 31136181
To improve understanding of pulmonary drug dissolution, four poorly soluble inhalation compounds (AZD5423 (a developmental nonsteroidal glucocorticoid), budesonide, fluticasone furoate (FF), and fluticasone propionate (FP)) were administered as suspensions or dry powders to the w …
To improve understanding of pulmonary drug dissolution, four poorly soluble inhalation compounds (AZD5423 (a developmental nonsteroidal gluc …
Drug Absorption Parameters Obtained Using the Isolated Perfused Rat Lung Model Are Predictive of Rat In Vivo Lung Absorption.
Eriksson J, Sjögren E, Lennernäs H, Thörn H. Eriksson J, et al. AAPS J. 2020 May 11;22(3):71. doi: 10.1208/s12248-020-00456-x. AAPS J. 2020. PMID: 32394314 Free PMC article.
Simulations using ex vivo input parameters were within twofold average difference (AAFE < 2) from experimental in vivo data for all compounds except one. ...

Simulations using ex vivo input parameters were within twofold average difference (AAFE < 2) from experimental in vivo data for al

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Safety, Pharmacokinetics and Pharmacodynamics of the Selective Glucocorticoid Receptor Modulator AZD5423 after Inhalation in Healthy Volunteers.
Werkström V, Prothon S, Ekholm E, Jorup C, Edsbäcker S. Werkström V, et al. Basic Clin Pharmacol Toxicol. 2016 Dec;119(6):574-581. doi: 10.1111/bcpt.12621. Epub 2016 Jul 8. Basic Clin Pharmacol Toxicol. 2016. PMID: 27214145 Free article. Clinical Trial.
Inhaled, nebulized AZD5423 was safe and well tolerated up to and including the highest doses tested for up to 2 weeks of once-daily treatment. Plasma exposure suggested dose-proportional pharmacokinetics and dose-related effects on 24-hr plasma and urine cortisol. ...AZD54 …
Inhaled, nebulized AZD5423 was safe and well tolerated up to and including the highest doses tested for up to 2 weeks of once-daily t …