megalin Inhibitors

Megalin Inhibitors target and modulate the activity of the megalin protein, also known as LRP2 (Low-Density Lipoprotein Receptor-Related Protein 2). Megalin is a large, multi-ligand endocytic receptor expressed on the cell surface of various tissues, particularly in the proximal tubules of the kidney and the absorptive epithelial cells of the small intestine. Structurally, megalin consists of several domains, including a series of cysteine-rich complement-type repeats that allow it to interact with numerous ligands and mediate their internalization into cells through endocytosis.

The functions of megalin are diverse and pivotal to various physiological processes, primarily related to the uptake and transport of ligands from the extracellular environment into cells. Megalin plays a central role in the reabsorption of essential proteins and nutrients from the glomerular filtrate in the kidneys, preventing their loss in urine. It is involved in the uptake of molecules such as vitamin D-binding protein, albumin, and hormones like insulin, thyroid hormones, and parathyroid hormone, among others. In the small intestine, megalin contributes to the absorption of dietary nutrients, vitamins, and other bioactive compounds. Additionally, megalin has been implicated in signaling pathways and cellular processes beyond endocytosis, including cell adhesion, intracellular signaling, and cellular differentiation.