{Reference Type}: Journal Article
{Title}: Small molecule and PROTAC molecule experiments in vitro and in vivo, focusing on mouse PD-L1 and human PD-L1 differences as targets.
{Author}: Awadasseid A;Wang R;Sun S;Zhang F;Wu Y;Zhang W;
{Journal}: Biomed Pharmacother
{Volume}: 172
{Issue}: 0
{Year}: 2024 Mar 12
{Factor}: 7.419
{DOI}: 10.1016/j.biopha.2024.116257
{Abstract}: In recent years, several monoclonal antibodies (mAbs) targeting PD-L1 have been licensed by the FDA for use in the treatment of cancer, demonstrating the effectiveness of blocking immune checkpoints, particularly the PD-1/PD-L1 pathway. Although mAb-based therapies have made great strides, they still have their limitations, and new small-molecule or PROTAC-molecule inhibitors that can block the PD-1/PD-L1 axis are desperately needed. Therefore, it is crucial to translate initial in vitro discoveries into appropriate in vivo animal models when creating PD-L1-blocking therapies. Due to their widespread availability and low experimental expenses, classical immunocompetent mice are appealing for research purposes. However, it is yet unclear whether the mouse (m) PD-L1 interaction with human (h) PD-1 in vivo would produce a functional immunological checkpoint. In this review, we summarize the in vitro and in vivo experimental studies of small molecules and PROTAC molecules, particularly the distinctions between mPD-L1 as a target and hPD-L1 as a target.