Phosphodiesterase type 11A (PDE11A)

Phosphodiesterase type 11A (PDE11A) is a dual-specificity enzyme responsible for the hydrolysis of both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby regulating critical intracellular signaling pathways [UniProt, ResearchGate]. It is uniquely expressed in specific tissues, including the prostate, skeletal muscle, adrenal glands, and the hippocampus [NIH, Eurekaselect]. PDE11A has been implicated in various pathologies; germline loss-of-function mutations are associated with a predisposition to endocrine tumors such as Cushing syndrome, Carney complex, and prostate cancer, while its overexpression is observed in glioblastoma [NIH, Semanticscholar]. In the central nervous system, PDE11A4 (a major splice variant) modulates hippocampal functions related to memory and social behavior, making it a potential target for neuropsychiatric disorders [NIH]. Clinically, PDE11 is a significant off-target for the PDE5 inhibitor tadalafil, and this cross-reactivity is believed to cause side effects such as myalgia and back pain [ResearchGate, NIH]. Ongoing research aims to develop selective PDE11A modulators to treat psychiatric conditions and malignancies while avoiding the side effects associated with broader phosphodiesterase inhibition [Eurekaselect, Patsnap].

Other names

PDE11cAMP and cGMP-inhibited phosphodiesterase 11ADual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A

Competitive inhibition of the catalytic site, preventing the hydrolysis of cAMP and cGMP into 5'-AMP and 5'-GMP, respectively [scbt.com, patsnap.com].