Compound class:
Synthetic organic
Comment: MIDD0301 is a positive allosteric GABAAR modulator [1]. MIDD0301 targets specific GABA receptor subtypes (α4- and α5-containing receptors) that are selectively expressed in airway smooth muscle, airway epithelium, and inflammatory cells [2-3], and in this way offers the potential to alleviate asthma pathophysiology with a reduced likelihood of causing systemic side effects. It acts both as a bronchodilator and as an anti-inflammatory agent.
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References |
1. Forkuo GS, Nieman AN, Kodali R, Zahn NM, Li G, Rashid Roni MS, Stephen MR, Harris TW, Jahan R, Guthrie ML et al.. (2018)
A Novel Orally Available Asthma Drug Candidate That Reduces Smooth Muscle Constriction and Inflammation by Targeting GABAA Receptors in the Lung. Mol Pharm, 15 (5): 1766-1777. [PMID:29578347] |
2. Gallos G, Yim P, Chang S, Zhang Y, Xu D, Cook JM, Gerthoffer WT, Emala Sr CW. (2012)
Targeting the restricted α-subunit repertoire of airway smooth muscle GABAA receptors augments airway smooth muscle relaxation. Am J Physiol Lung Cell Mol Physiol, 302 (2): L248-56. [PMID:21949156] |
3. Gallos G, Yocum GT, Siviski ME, Yim PD, Fu XW, Poe MM, Cook JM, Harrison N, Perez-Zoghbi J, Emala Sr CW. (2015)
Selective targeting of the α5-subunit of GABAA receptors relaxes airway smooth muscle and inhibits cellular calcium handling. Am J Physiol Lung Cell Mol Physiol, 308 (9): L931-42. [PMID:25659897] |