Broad Spectrum Mixed Lineage Kinase Type 3 Inhibition and HIV-1 Persistence in Macrophages.

ABSTRACT: Mixed lineage kinases (MLKs) are a group of serine-threonine kinases that evolved in part to respond to endogenous and exogenous insults that result in oxidative stress and pro-inflammatory responses from innate immune cells. Human immunodeficiency virus type 1 (HIV-1) thrives in these conditions and is associated with the development of associated neurocognitive disorders (HAND). As part of a drug discovery program to identify new therapeutic strategies for HAND, we created a library of broad spectrum MLK inhibitors with drug-like properties. Serendipitously, the lead compound, URMC-099 has proved useful not only in reversing damage to synaptic architecture in models of HAND, but also serves to restore autophagy as a protective response when given in concert with nanoformulated antiretrov

SUBMITTER: Saminathan P 

PROVIDER: S-EPMC6391203 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature