Transcription
Hey guys, it's Medicos is Perfection Alice. Today, let's talk about the miraculous tyrosine kinase inhibitors. These are indeed revolutionary drugs. The TKIs is the topic of today's video. But before you know more about tyrosine kinase inhibitors, let's first talk about the tyrosine kinase enzyme. It's an enzyme because it ends in "-ase." Kinase means it's an enzyme that will add a phosphate group. Perfect.
Now, let's talk about the tyrosine kinase enzyme. Will add phosphate group? Where did you get it from? From the ATP, the famous adenosine triphosphate. It will take the phosphate group from the ATP and put it on a protein. Perfect. Now, the ATP - one phosphate equals ADP, adenosine diphosphate, and this protein now has a phosphate group. It's called a phosphorylated protein. Phosphorylated proteins aid in signal transduction. Think about it as the on/off switch for the cell. You turn it on or turn it off through phosphorylation.
What is the molecular target? BCR-Abel. What's the mechanism of action? They block ATP binding to tyrosine kinase active site. So if here is the tyrosine kinase and here is the ATP, they bind together in an active site. These tyrosine kinase inhibitors will block this active site, so ATP and tyrosine kinase cannot bind together. So we cannot transfer this phosphate group from the ATP into the protein. Thus, tyrosine kinase inhibitor.
In my previous video on chronic myeloid leukemia, I've talked about the Philadelphia chromosome. You have a fusion gene, fusion protein, which acts as a tyrosine kinase. This is an on switch for cancer. How to prevent it? By using a tyrosine kinase inhibitor. Talk about imatinib in greater details. As you know, imatinib, it ends in "-nib," so it's a protein kinase inhibitor. What's the target? It has many targets. If the target is the BCR-Abel fusion protein, it can be used to treat chronic myeloid leukemia or the Philadelphia chromosome-positive acute lymphoblastic leukemia. Both of them have 9;22 translocation. Make sense? Also, if the target is c-Kit mutant, again a tyrosine kinase, you can use imatinib to treat GIST, or gastrointestinal stromal tumors. If the target is platelet-derived growth factor receptor, this imatinib can be used to treat MDS as well as some myeloproliferative syndromes.
That being said, what are the side effects of imatinib? First, you have nausea. And don't forget, imatinib is notoriously fluid retention, such as periorbital edema as well as congestive heart failure. Imatinib can prolong the QT interval on the EKG. Sometimes it's written as QTc, same thing, QT interval corrected. Side effects of other tyrosine kinase inhibitors: myelosuppression, nilotinib interaction with the CYP3A4 system in the liver as well as GI and liver toxicity, but certain bone marrow suppressions. TKIs are teratogenic, so be aware, pregnancy is a no-no.
Generally speaking, any questions on my Facebook page? Also, I post lots of stuff there, SoundCloud, and if you'd like to support this channel on Patreon to help me produce more videos in the future, thank you. This is Medicos is Perfection Alice. Be safe, stay happy, and study hard.