Development of a novel pharmacophore model to screen specific inhibitors for the serine-threonine protein phosphatase calcineurin.

ABSTRACT: Calcineurin (CaN) is a calcium/calmodulin-dependent serine/threonine phosphatase with a crucial role in cellular homeostasis. It is also the target of the Food and Drug Administration (FDA) approved immunosuppressant drugs FK506 and cyclosporine A. Recent work from our group and others indicated that an uncontrolled increase in CaN activity causes synaptic dysfunction and neuronal death in various models of neurodegenerative diseases associated with calcium dysregulation. Furthermore, pharmacological normalization of CaN activity can prevent disease progression in animal models. However, none of the FDA-approved CaN inhibitors bind CaN directly, leading to adverse side effects. The development of direct CaN inhibitors is required to reduce off-target effects, but its highly conserved activ

SUBMITTER: Mukherjee A 

PROVIDER: S-EPMC9398911 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature