Chemotherapy and Its Side Effects: Chapter 2 - Kinase Modulators (cont'd)

E.1. Imatinib mesylate (sold as Gleevec® by Novartis)

Fig. 1.12

Imatinib (Fig. 1.12) was first approved by the FDA in 2001 and sold as Gleevec^®. It works by specifically targeting, and turning off constitutively active tyrosine kinases (Bcr-abl) which help cancer cells grow and multiply. Bcr-abl kinase is a hybrid product of a chimeric Bcr-abl oncogene caused by translocation between chromosomes 9 and 22. The tyrosine kinases cause several cancers including Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) and gastrointestinal stromal tumor (GIST). Gleevac comes in tablet form. When given by oral administration, the active ingredient, imatinib, is rapidly absorbed.

Potential side effects of Gleevec include fluid retention, rash, nausea & vomiting, muscle cramps, and diarrhea. 

© Jiajiu Shaw, 2019

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen. 

Chemotherapy and Its Side Effects: Chapter 2 - Kinase Modulators

Chapter 2

Anticancer Drugs - E. Kinase Modulators

A protein kinase modifies a specific protein (substrate) by chemically adding a phosphate group (from ATP) to change the function/activity of the substrate that regulates the cellular pathways, especially signal transduction pathways. This process of adding a phosphate group to a substrate is referred to as phosphorylation. During the phosphorylation process, ATP loses a phosphate group and becomes ADP.

Phosphorylation is a very important reaction, which regulates a lot of biological processes. The phosphate groups are often added to tyrosine, threonine, or serine. As a result of the phosphorylation, many biological processes are regulated. Many diseases are due to the hyperactivity of protein kinases. Therefore, it makes sense to tackle these diseases by modulating the protein kinases.

More than 500 protein kinases have been identified in humans. For example, tyrosine kinase is an enzyme that helps attach a phosphate group onto a tyrosine residue in a protein; it is important in signal transduction and is implicated in the treatment of cancer.

Kinase modulators target a molecular abnormality by modulating the activity of certain kinase. Kinase modulators have been used in certain types of cancer. Examples of kinase modulators are shown below. 

© Jiajiu Shaw, 2019

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen.