Proline Kinase Library

ChemDiv’s Proline Kinase Inhibitors Library contains 2,000 compounds.

Phosphorylation motifs consisting of serine or threonine residues followed by proline (Ser/Thr-Pro) are critical regulatory elements in numerous cellular processes. Phosphorylation of these motifs is primarily mediated by a family of Pro-directed protein kinases, including cyclin-dependent protein kinases (CDKs), mitogen-activated protein kinases (MAPKs), Jun N-terminal protein kinases (JNKs), and glycogen synthase kinase-3 (GSK-3). Conversely, the dephosphorylation of these motifs is carried out by specific Ser/Thr phosphatases, such as phosphatase 2A (PP2A), the RNA polymerase II C-terminal domain (RNA Pol II CTD) phosphatase FCP1, and calcineurin. These kinases and phosphatases are integral to numerous cellular functions, including the cell cycle, transcription regulation, and various signaling pathways. Modulation of the Ser/Thr phosphorylation often involves conformational changes in proteins, affecting their function and interactions. Their dysregulation is implicated in a range of human diseases, in particular cancer and Alzheimer’s disease.

Inhibitors of proline kinases play a marked role in drug discovery, targeting key enzymes mentioned above: CDKs, MAPKs, GSK-3, and JNKs. These inhibitors are the primary agents in treating various cancers by blocking cell cycle progression and aberrant cell growth, as seen with CDK inhibitors. In clinical cancer therapy, MAPK inhibitors are used to target faulty signaling pathways in melanoma. Beyond oncology, GSK-3 inhibitors are under investigation for neurodegenerative diseases like Alzheimer’s, whereas JNK inhibitors are being explored for inflammatory diseases and certain neurodegenerative disorders. By binding to the active sites of these kinases, these drugs disrupt dysfunctional signaling pathways, making them valuable in the development of targeted therapies for a range of diseases.

Chemdiv’s proline kinase inhibitors library provides an extended set of diverse hit molecules with high affinity and specificity to the proline kinase enzymes, making it a potential starting point for the drug discovery research study.

References:
[1] K. P. Lu, Y. C. Liou, and X. Z. Zhou. Pinning down proline-directed phosphorylation signaling. Trends Cell Biol., 2002, vol. 12, no. 4, pp. 164–172, doi: 10.1016/S0962-8924(02)02253-5.