A class of drugs known as protein kinase inhibitors prevents protein kinases—the enzymes that phosphorylate proteins by adding phosphate groups—from doing their job. An essential regulatory mechanism in cells, phosphorylation governs a range of cellular processes, including growth, differentiation, metabolism, and apoptosis. Protein kinase inhibitors are useful therapeutic drugs because..
A class of drugs known as protein kinase inhibitors prevents protein kinases—the enzymes that phosphorylate proteins by adding phosphate groups—from doing their job. An essential regulatory mechanism in cells, phosphorylation governs a range of cellular processes, including growth, differentiation, metabolism, and apoptosis. Protein kinase inhibitors are useful therapeutic drugs because dysregulation of protein kinases can cause diseases, including malignancies.Protein kinases come in different varieties, such as tyrosine kinases and serine/threonine kinases, which get their names from the amino acids they phosphorylate. In cancer treatment, tyrosine kinase inhibitors (TKIs) are very common. By limiting the transfer of phosphate groups and consequently impeding signal transduction pathways essential for tumor growth and survival, these inhibitors specifically target the ATP-binding site of tyrosine kinases.Imatinib (Gleevec), which targets the BCR-ABL fusion protein generated by the Philadelphia chromosome in chronic myeloid leukemia (CML), is one of the first and most well-known TKIs. Due to imatinib's effectiveness, many new TKIs have been developed, including sunitinib (Sutent), which targets various tyrosine kinases involved in tumor angiogenesis and growth, and erlotinib (Tarceva), which targets the epidermal growth factor receptor (EGFR).Protein kinase inhibitors are being investigated for disorders other than cancer. For example, rheumatoid arthritis and psoriasis are two inflammatory and autoimmune disorders that are treated with inhibitors that target Janus kinases (JAKs). Tofacitinib, also known as Xeljanz, is a well-known JAK inhibitor.Because protein kinase inhibitors affect normal cellular processes, they can have considerable adverse effects despite their potential for therapeutic use. Skin rashes, stomach problems, and cardiovascular problems are typical adverse effects. Long-term efficacy of kinase inhibitors can also be hampered by resistance that can arise from a variety of reasons, including kinase domain mutations or the activation of alternate signaling pathways.The goal of ongoing research is to better understand resistance mechanisms and to design more selective inhibitors with fewer side effects. Protein kinase inhibitor treatments are becoming more precise and efficacious as a result of ongoing advancements in combination therapy and next-generation inhibitor design.
