PI3K Inhibitor Buparlisib (BKM120): What Is It & How Does It Work?

There are various pathways operating in cancer biology that scientists are studying nowadays, in an effort to come to certain discoveries and figure out how to develop new treatments that will target those pathways specifically, and potentially help patients fight this condition much more successfully. While they were once focused specifically on learning how to kill cancer cells, researchers now understand the significance of cutting off certain supplies in our bodies that signal and allow the tumor cells to grow and proliferate. So, the research focus has shifted, although the core idea still remains the same – curing cancer.

The PI3K/AKT/mTOR pathway is one of those highly significant ones that scientists are nowadays interested in understanding better. This is a pathway that actually regulates cell survival, growth, metabolism and proliferation, and it is quite often dysregulated in tumors, meaning that it can be overactive and result in tumors growing uncontrollably. I suppose you understand that its excessive activity is rather unfavorable in this case.

Due to this, scientists have been looking for ways to sort of disrupt this pathway, and inhibiting PI3K has, therefore, come up as the focus of a lot of research processes. Well, Buparlisib (BKM120) PI3K inhibitor has been developed as a drug that can do that necessary work. Since you are here, it is safe to say that you are interested in understanding this particular inhibitor better, and that you want to get a better idea about what it is and how it works. 

The good news is that those are precisely the topics that we are going to cover below. So, if you want to learn a bit more about all of this, whether as a researcher, or simply someone who likes gaining knowledge on these types of scientific developments, then you should undeniably keep on reading. Below we will answer those important questions for you, shedding light on what you need to know about this particular substance.

What Is Buparlisib (BKM120) PI3K inhibitor?

Clearly, we are going to begin with the most basic question of them all. The question of what Buparlisib (BKM120) PI3K inhibitor is in the first place. To cut right to the chase, we are talking about a small molecule inhibitor that targets specifically the class I of PI3K isoforms. The idea is for it to inhibit the catalytic activity of the PI3K enzyme family, and that is precisely what it does, with varying potencies.

It also has some effects on other kinases, such as mTOR, although its potency is more limited there. Another important thing to note here is that Buparlisib (BKM120) PI3K inhibitor shows to be able to cross the blood-brain barrier, which is pretty rare in some other PI3K inhibitors. And, this makes it potentially useful in brain cancer settings. Apart from all of this, another thing to know is that this drug is administered orally, which is definitely highly convenient.

How Does It Work?

How does this particular chemical actually work? Well, let us now explain that in simple words, so that anyone reading can understand, regardless of the actual level of knowledge when it comes to oncology, cells, molecules, and medicine in general. And, as you will see, the mechanism behind it really isn’t that complicated at all.

Basically, it binds to the ATP-binding pocket of the class I PI3K subunits with catalytic properties, aiming at actually blocking their enzymatic activity. This, through its own mechanisms, lowers the downstream AKT activation, as well as mTOR signaling. That further means that the cells get less survival signaling, which increases their propensity towards apoptosis, altered metabolism, reduced proliferation, and cell cycle arrest. In simple words, cancer cells get fewer signals that it is time for them to grow, divide and survive, which eventually leads to them being more vulnerable and more sensitive to treatment, as well as to, of course, dying.

Here is an interesting study about it you may want to read: https://www.annalsofoncology.org/article/S0923-7534(19)52727-2/fulltext 

What Are Its Advantages?

So, now you understand what Buparlisib (BKM120) PI3K inhibitor is, and you have a better idea about its mechanism of work. What you want to do next is actually understand what its advantages are, because that will give you a better idea about its importance, and about why it is that it is being so extensively used in research nowadays. Well, there are, without a doubt, some important advantages to keep in mind here, and I am now going to tell you about some of those, hoping to help you get a clearer understanding of everything.

First things first, there is the fact that Buparlisib (BKM120) PI3K inhibitor targets all class I isoforms. This is a huge advantage, because this type of extensive coverage means that it can potentially block the compensatory pathway escape via alternate isoforms. In a word, it appears to be highly effective, and that is undeniably a huge benefit.

Apart from that, we cannot fail to mention the fact that it is administered orally. Why is this worth mentioning, though? Well, because it provides patients with much more convenience than some other forms of therapy, such as those relying on intravenous agents. Taking this drug is much easier and it doesn’t require frequent visits to hospitals.

Another thing that makes Buparlisib (BKM120) PI3K inhibitor stand out is the fact that it can cross the blood-brain barrier (BBB). This makes it a valuable tool for researching brain tumors, as well as for treating them. It opens up the doors to new findings when it comes to brain tumors and metastases.

To Sum Up

So, let us now quickly sum up what we have learned about Buparlisib (BKM120) PI3K inhibitor. Basically, it is a small molecule drug that targets all class I isoforms of PI3K, which makes it highly effective. Taken orally, this drug is highly convenient.

It is used in research for various forms of cancer, and it has undeniably proven to be highly useful. Then, being able to cross BBB, it has become a valuable research tool in brain cancer as well. That is what we know so far, but who knows what the future holds and what new discoveries may be awaiting.