Y3154207 is a novel, potent, and subtype selective human D1 positive allosteric modulator (PAM) with minimal allosteric agonist activity (EC50 = 3 nM). In contrast to orthosteric agonists, LY3154207 showed a distinct pharmacological profile without a bell-shaped dose-response relationship or tachyphylaxis in preclinical models. Identification of a crystalline form of free LY3154207 from the discovery lots was not successful. Instead, a novel cocrystal form with superior solubility was discovered and determined to be suitable for development. LY3154207 is now in clinical development as a potential first-in-class D1 PAM for Lewy body dementia.
LY3154207 is a potent, orally bioavailable, and subtype-selective positive allosteric modulator (PAM) of the human dopamine D1 receptor, possessing minimal allosteric agonist activity (EC50=3 nM)[1].
体外研究
In HEK293 cells transiently expressing D1 receptors from humans, dogs, rhesus monkeys, and mice, LY3154207 exhibits EC50 values of 2.3 nM, 2.0 nM, 2.5 nM, and 62.1 nM, respectively[1].
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