Pamiparib (maleate)

Pamiparib maleate (BGB-290 maleate) is a highly potent and selective PARP inhibitor with neurotoxicity-inducing activity. Pamiparib maleate can effectively penetrate the blood-brain barrier and cause cerebral hemorrhage, brain atrophy, and movement disorders in zebrafish embryos exposed. Pamiparib maleate exposure downregulates the activities of acetylcholinesterase (AChE) and adenosine triphosphatase (ATPase) and leads to upregulation of oxidative stress, which triggers apoptosis and interferes with the expression of neurodevelopment-related genes. The use of pamiparib maleate is also accompanied by downregulation of the Notch signaling pathway, while activation of the Notch signaling pathway can partially rescue neurodevelopmental toxicity. Therefore, pamiparib maleate provides a reference for evaluating its potential neurotoxicity during embryonic development[1].