ITI-214 free base is a potent, CNS-active, orally bioavailable PDE1 inhibitor (K_i of 58 pM) with excellent selectivity against other PDE family members and against a panel of enzymes, receptors, transporters and ion channels. ITI-214 free base inhibits recombinant full-length human PDE1A, PDE1B and PDE1C with K_is of 33 pM, 380 pM and 35 pM, respectively. ITI-214 free base shows efficacy in various animal models of motor and cognitive functions.

ITI-214 is found to potently inhibit the activity of full-length recombinant r-hPDE1A (K_i= 34 pM), r-hPDE1B (K_i= 380 pM), and r-hPDE1C (K_i= 37 pM) enzymes transiently expressed in HEK cells. The compound expressed >1000-fold greater activity toward PDE1 isoforms compared with the next nearest PDE family enzyme, PDE4D (K_i= 33 nM) and 10,000-300,000-fold selectivity toward all other PDE enzyme families.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

ITI-214 significantly enhances memory performance in the test with a minimum effective dose of 3 mg/kg.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

ITI-214 significantly enhances memory performance in the test with a minimum effective dose of 3 mg/kg.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Li P, et al. Discovery of Potent and Selective Inhibitors of Phosphodiesterase 1 for the Treatment of Cognitive Impairment Associated with Neurodegenerative and Neuropsychiatric Diseases. J Med Chem. 2016 Feb 11;59(3):1149-64.  [Content Brief]

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