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Description: AZD5423 is the first clinical candidate that displayed a potent inhibition of lung edema in a rat model of allergic airway inflammation following dry powder inhalation combined with a moderate systemic GR-effect, assessed as thymic involution. Further optimization of inhaled drug properties provided a second, equally potent, candidate, AZD7594 (also known as AZ13189620), which is a novel, potent selective nonsteroidal indazole ether-based glucocorticoid receptor modulators (SGRMs) with an IC50 of 0.9 nM. AZD-7594 is an inhaled selective glucocorticoid receptor (GCCR) modulator for the inhaled treatment of respiratory diseases. AZD7594 demonstrated an improved therapeutic ratio over the benchmark inhaled corticosteroid 3 (fluticasone propionate) and prolonged the inhibition of lung edema, indicating potential for once-daily treatment. AZD-7594 is currently in phase II clinical trials by AstraZeneca for the treatment of mild to moderate asthma. It is also in phase I clinical trials for the treatment of chronic obstructive pulmonary disorder (COPD).
References: J Med Chem. 2017 Oct 26; 60(20):8591-8605.
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