Kinase inhibitor

Kinase inhibitor
Drug class
Class identifiers
ATC code	L01

Kinase inhibitors are a class of pharmaceutical drugs that block or inhibit the enzymatic activity of one or more protein kinases. Protein kinases are enzymes that add a phosphate group to a protein, a process known as phosphorylation. Phosphorylation is a key mechanism in cell signaling, which controls most cellular processes, including metabolism, transcription, cell cycle progression, cytoskeletal rearrangement, and cell movement. By inhibiting specific kinases, these drugs can interfere with the pathways that promote cell division, growth, and survival.

Mechanism of Action

Kinase inhibitors work by binding to the ATP-binding site of a kinase, preventing the transfer of a phosphate group from ATP to a protein substrate. This inhibition can be achieved through competitive or non-competitive mechanisms, depending on the drug and the target kinase. The specificity of kinase inhibitors can vary; some are designed to be highly selective for a single kinase, while others inhibit a broader range of kinases.

Clinical Uses

Kinase inhibitors are primarily used in the treatment of cancer, where they help to stop the growth and spread of cancer cells by targeting specific kinases involved in tumor growth and progression. Examples include imatinib (Gleevec), which targets BCR-ABL kinase in chronic myeloid leukemia, and trastuzumab (Herceptin), which targets the HER2/neu kinase in breast cancer.

In addition to cancer, kinase inhibitors are also used in the treatment of other diseases. For instance, tofacitinib is used to treat rheumatoid arthritis by inhibiting Janus kinases, which are involved in the inflammation process.

Development and Approval

The development of kinase inhibitors involves identifying suitable kinase targets associated with specific diseases, followed by the design and optimization of inhibitors that can effectively and selectively block these kinases. Clinical trials are conducted to assess the efficacy, safety, and dosage of these drugs. Upon successful trials, drugs are submitted for regulatory approval.

Side Effects

The side effects of kinase inhibitors can vary depending on the specific drug and the kinases it targets. Common side effects include fatigue, nausea, vomiting, diarrhea, and skin rashes. More severe side effects can include liver toxicity, heart problems, and an increased risk of infections due to immunosuppression.

Future Directions

Research continues to identify new kinase targets and develop more selective and potent inhibitors. The use of kinase inhibitors is also expanding into other therapeutic areas, including metabolic diseases, neurological disorders, and inflammatory conditions.

See Also

• Pharmacology
• Oncology
• Signal transduction
• Targeted therapy