Wow, sounds like a game changer. A totally different mechanism with almost no effect on healthy cells and it can be used as an adjunct to other chemotherapies? I mean, if it pans out, wow, that would be amazing. I remember reading about how with HIV if you have 1 drug it works for a while but evolves out from under you, 2 drugs extends this time, and a third just flattens it so much there isnt enough popation to mutate away. In the same way adding this as an adjunct could prevent the drift which can happen to some cancers when under selection from a chemo drug. Exciting times.
It may be semi proven and semi available soon. The synthesis looks quite simple so they will probably knock it out in less regulated countries like India or China.
Not a medical chemist, but I noticed that three AOH1996 molecules are binding to PCNA. Would it make sense to chain together three AOH1996 molecules with flexible linkers for, I don't know, increased specificity or something like that?
Am i the only one wondering what this finding really means in practice when we read every other weak a similiar science article that claims to be a breakthrough in cancer treatment?
Like solar cell and battery material discoveries, there is an ocean of problems to overcome before the promising results flow into a product. Potentially decades of problems to solve.
>> Shkreli bought the exclusive rights to manufacture Daraprim, a drug that can treat a rare parasitic disease, in 2015 and hiked the price from $13.50 per pill to $750, to much controversy. The entrepreneur was ordered in January 2022 to return $64.6 million in profit made by the price hikes and creating what the Federal Trade Commission alleged was “a web of anti-competitive restrictions” to prevent rivals from making a cheaper generic version.
His history is "fine", if you consider that this is par for the course for the pharma industry. Acquiring IP rights to a drug, then ratcheting the price is a tale as old as time.
Shkreli's main sin is choosing a drug that is primarily used by a specific protected class. It treats parasitic infections that normally don't take hold in people with healthy immune response. Daraprim's customer list is something like 92% AIDS patients, and 8% immuno-compromised for other reasons.
Shkreli did something that happens all the time, and we don't bat an eye. But you don't do it to protected classes without a mob response.
Virtual screening[1] is a computational technique where you take an experimentally resolved structure of a protein (PCNA in this case) and sequentially dock a large amount of different compounds to see which ones of them bind favorably to the target protein. It is worth mentioning that virtual screening is a very early step in a drug discovery pipeline. These hits need to be characterized and validated experimentally to see if there is an actual effect.
I am not well-versed in intellectual property (so please correct me if I’m wrong), but in this case Shkreli is using a database of commercially available compounds (ZINC) and a hit present in the screen could be patented. He said he won’t do it, and, since this could be considered prior art, nobody else can do a claim.
A sentence near the end of the article summarizes why cancer is such a nasty disease to deal with:
"I hope that human cancers will prove vulnerable to this new mode of attack in the clinic, and that *they are not able to mutate around it with new forms of caPCNA too quickly*, either."
The compound might have additional mutagenic mechanisms apart from the described PCNA interaction: it could cause direct chemical modifications to DNA, act as an intercalating agent that disrupts DNA replication and/or transcription, etc.
Readit News
I hope we're entering a new epoch. The number of people I've met who've lost loved ones too early.
That dragon, cancer. https://en.wikipedia.org/wiki/That_Dragon,_Cancer
I feel that I'm in good hands. If I was rich, I'd maybe get better care from some more expensive hands but there's no guarantee.
>> Shkreli bought the exclusive rights to manufacture Daraprim, a drug that can treat a rare parasitic disease, in 2015 and hiked the price from $13.50 per pill to $750, to much controversy. The entrepreneur was ordered in January 2022 to return $64.6 million in profit made by the price hikes and creating what the Federal Trade Commission alleged was “a web of anti-competitive restrictions” to prevent rivals from making a cheaper generic version.
https://www.fastcompany.com/90932968/martin-shkreli-dr-gupta...
Shkreli's main sin is choosing a drug that is primarily used by a specific protected class. It treats parasitic infections that normally don't take hold in people with healthy immune response. Daraprim's customer list is something like 92% AIDS patients, and 8% immuno-compromised for other reasons.
Shkreli did something that happens all the time, and we don't bat an eye. But you don't do it to protected classes without a mob response.
I am not well-versed in intellectual property (so please correct me if I’m wrong), but in this case Shkreli is using a database of commercially available compounds (ZINC) and a hit present in the screen could be patented. He said he won’t do it, and, since this could be considered prior art, nobody else can do a claim.
[1]: https://en.wikipedia.org/wiki/Virtual_screening
"I hope that human cancers will prove vulnerable to this new mode of attack in the clinic, and that *they are not able to mutate around it with new forms of caPCNA too quickly*, either."