Tyrosine kinase inhibitor

Structure of Abl1 bound to Nilotinib, a tyrosine kinase inhibitor.

A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits the function of tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. They are a subclass of protein kinases that specifically phosphorylate the amino acid tyrosine on target proteins.

Mechanism of Action

Tyrosine kinase inhibitors work by blocking the ATP binding site of the tyrosine kinase enzyme. This prevents the phosphorylation of tyrosine residues on substrate proteins, thereby inhibiting the downstream signaling pathways that promote cell division and survival. This mechanism is particularly useful in treating cancers where these pathways are abnormally activated.

Clinical Applications

TKIs are primarily used in the treatment of various types of cancer, including:

• Chronic myeloid leukemia (CML)
• Non-small cell lung cancer (NSCLC)
• Renal cell carcinoma
• Gastrointestinal stromal tumors (GIST)

Examples of Tyrosine Kinase Inhibitors

Some well-known tyrosine kinase inhibitors include:

• Imatinib (Gleevec)
• Nilotinib (Tasigna)
• Erlotinib (Tarceva)
• Gefitinib (Iressa)

Side Effects

Common side effects of TKIs can include:

• Fatigue
• Nausea
• Diarrhea
• Skin rash
• Edema

Resistance

Resistance to tyrosine kinase inhibitors can develop through various mechanisms, such as mutations in the kinase domain of the target enzyme, activation of alternative signaling pathways, or increased drug efflux. This is a significant challenge in the long-term management of cancer patients on TKI therapy.

Related Pages

• Protein kinase
• Signal transduction
• Cancer treatment