Kinasehemmern

Kinasehemmern are a class of therapeutic agents that inhibit the activity of protein kinases, enzymes that catalyze the transfer of phosphate groups to substrates. By blocking phosphorylation, they interrupt signaling pathways that control cell growth, survival, differentiation, and metabolism. Kinasehemmern can be small molecules or biologics and may act competitively at the ATP-binding site, bind allosteric sites, or form irreversible bonds with the target kinase. They range from highly selective inhibitors targeting a single kinase to multi-target agents that affect several kinases simultaneously.

Clinical use and targets

Kinasehemmern are widely used in oncology, where many cancers harbor dysregulated kinase signaling. Examples include imatinib, a BCR-ABL inhibitor used in chronic myeloid leukemia; erlotinib and gefitinib, EGFR inhibitors for certain lung cancers; sorafenib and sunitinib, multi-kinase inhibitors for liver, kidney, and gastrointestinal cancers; and vemurafenib, a BRAF V600E inhibitor for melanoma. In autoimmune and inflammatory diseases, JAK inhibitors such as tofacitinib suppress cytokine signaling. Other inhibitors target PI3K, mTOR, or HER family kinases and are used in various hematologic and solid tumors.

Mechanisms and challenges

By preventing kinase activity, these agents alter downstream pathways like MAPK and PI3K–AKT–mTOR, leading to reduced proliferation or induced cell death. Challenges include acquired resistance through mutations, activation of bypass pathways, and toxicity to normal tissues. Adverse effects vary by target but commonly include rash, fatigue, cytopenias, liver enzyme elevations, and edema.

Status and development

Kinasehemmern are a cornerstone of precision medicine, with ongoing development to improve selectivity, overcome resistance, and expand indications. Biomarker-driven patient selection remains central to maximizing therapeutic benefit.