Difficulty in finding protein inhibition drugs?

Question

I was reading an article on a recent identification of a PARP-14 protein in cancer cells that is responsible for production of additional glucose which keeps cancer cells from dying, and that a PARP-14 inhibiting drug is still a long way from becoming reality. Would like to ask any medical researchers/anyone with adequate knowledge, what is the difficulty in producing drugs that inhibit production by a certain protein? Isn't it about analyzing the chemical makeup and structure of the protein and finding ways to neutralize it? As how other types of drugs are made?

Answer 1

Wow lets see.

1. That you always see them with letter and name descriptions like PARP-14 should clue you in that there's too many of them to give them english names. There are, in this case 13 previous PARPs.
2. Protiens are very complex molecules, averaging  466 amino acids, with there being at least 20 types widely used. So many permutations the human mind can't grasp numbers that big. Being so very small, it is very difficult to model one, I mean I consider it mind-blowing that they even CAN.
3. They are capable of multiple configurations, even it you know what the order is you need to target the right configuration.

Then you have 2 routes to go:

Is the protein expressed on the outside of the cell? Then you're darn lucky, it might be possible to produce a monoclonal antibody that will trigger your immune system to attack anything with it. Of course, you also better hope you don't need anything with it. Maybe you'll get something, that will work but it will be very expensive ($2000/dose+)

If it is inside the cell, you likely can't reach it directly with any drug. So now you have to research how and why that protein gets made. This may involve a complex hormone cascade. Or finding exactly where on which gene it is on ,finding out how that gene is switched on and off, Once you have done all of that, you have to figure out something that will block the hormone, flip the switch on/off, etc.

Now, suppose you have that, you have a drug that may or may not work and may or may not be safe

(Make an immune globulin that say "attack this potassium-calcium ion exchange protein" and you have a drug that tells your immune system to kill every muscle in your body.

The process on average takes 12-20 years and costs many millions. And if you can poove to the FDA it i s safe and effective, it gets to market.

The original way drugs were is that we found natural compounds that are relatively simple that has an effect on the body. Then went about trying to synthesize better versions of it. - which was a lot shorter but a lot less involved than the methods above but also pretty random,

In any case, I hope I've impressed upon you the basic fact that identifying a protein involved in cancer is only piece #1 of a very large jigsaw puzzle. That may or may not have a solution. It's the part where you found one piece for sure and have to find or invent another, and another, and so on.