Anyone used 3bp (3-bromopyruvate)?

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RE: Anyone used 3bp (3-bromopyruvate)?

by dumbcritic on Thu Mar 11, 2021 10:11 PM

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Nirogy Therapeutics lead program is a dual MCT1/4 inhibitor, which should enter into clinical trials next year https://www.abstractsonline.com/pp8/#!/9325/presentation/238

RE: Anyone used 3bp (3-bromopyruvate)?

by Jcancom on Thu Mar 11, 2021 11:45 PM

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critic, thank you very much for posting this. Unfortunately, we have often been stranded in discussing non-optimized therapy directed at metabolic targets. When targets finally do make it through as products of 21st century medical engineering it can be highly impressive. It demonstrates the power of current medical chemistry to make highly potent anti-cancer pharmaceuticals.

(The HK2-VDAC target that you mentioned is especially impressive. The common place notion that cancer is indistinguishable from normal cells is time and time again shown not to be accurate.)   

However, the problem that remains is how to treat the millions and millions of patients every year that need access to what we can do now and not decades into the future with space age medicine. Admittedly 3-BP and others like it might not beaestheticallyor scientifically pleasing, though if they can be shown to get the job done, then who are we to tell the tens of millions of cancer patients that they will need to wait those decades?

RE: Anyone used 3bp (3-bromopyruvate)?

by dumbcritic on Sat Mar 13, 2021 11:02 PM

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On Mar 11, 2021 11:45 PM Jcancom wrote:

critic, thank you very much for posting this. Unfortunately, we have often been stranded in discussing non-optimized therapy directed at metabolic targets. When targets finally do make it through as products of 21st century medical engineering it can be highly impressive. It demonstrates the power of current medical chemistry to make highly potent anti-cancer pharmaceuticals.

(The HK2-VDAC target that you mentioned is especially impressive. The common place notion that cancer is indistinguishable from normal cells is time and time again shown not to be accurate.)   

However, the problem that remains is how to treat the millions and millions of patients every year that need access to what we can do now and not decades into the future with space age medicine. Admittedly 3-BP and others like it might not beaestheticallyor scientifically pleasing, though if they can be shown to get the job done, then who are we to tell the tens of millions of cancer patients that they will need to wait those decades?

Yes, not only is the second point true, but deregulated metabolism is arguably one of the more important of the ten hallmarks, and far more homogeneous across different types and stages than genome instability, which varies from cell to cell, between tumours, and person to person https://www.nejm.org/doi/full/10.1056/nejmoa1113205

We know that dual inhibition of MCT1 and MCT4 would likely synergise when combined with an OXPHOS inhibitor. There are a few drugs in development for the later (some could be made more potent), and now at least one moving forward that targets the former.

In terms of development, and assuming there is single-agent activity of the agent in dose escalation, enriching for (sub) types and/or patient populations most likely to have a better response (tumour shrinkage) in the dose expansion of the PhI would make the most sense. After this, a company (in agreement with a regulatory agency, such as the FDA) could move forward with registration directed PhII trials. If successful, it would save time and money, bringing the agent to market more quickly.

RE: Anyone used 3bp (3-bromopyruvate)?

by dumbcritic on Sat Mar 27, 2021 06:33 PM

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A new synthetic small molecule, which is a pan-class I GLUT inhibitor https://cancerandmetabolism.biomedcentral.com/articles/10.11

An older paper (using a different small molecule plus CB-839) https://www.sciencedirect.com/science/article/pii/S245194561

RE: Anyone used 3bp (3-bromopyruvate)?

by dumbcritic on Sun Apr 11, 2021 02:43 AM

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An oral PKM2 activator is now in the clinic https://www.abstractsonline.com/pp8/#!/9325/presentation/150

RE: Anyone used 3bp (3-bromopyruvate)?

by dumbcritic on Sun Apr 11, 2021 02:46 AM

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RE: Anyone used 3bp (3-bromopyruvate)?

by dumbcritic on Sun Apr 11, 2021 02:48 AM

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On Mar 11, 2021 10:11 PM dumbcritic wrote:

Nirogy Therapeutics lead program is a dual MCT1/4 inhibitor, which should enter into clinical trials next year https://www.abstractsonline.com/pp8/#!/9325/presentation/238 8"" target="_blank" rel="nofollow">https://www.abstractsonline.com/pp8/#!/9325/presentation/238 target="_blank" rel="nofollow">https://www.abstractsonline.com/pp8/#!/9325/presentation/238

A second https://www.abstractsonline.com/pp8/#!/9325/presentation/235

RE: Anyone used 3bp (3-bromopyruvate)?

by dumbcritic on Sun Apr 11, 2021 03:01 AM

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On Apr 11, 2021 2:48 AM dumbcritic wrote:

On Mar 11, 2021 10:11 PM dumbcritic wrote:

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rel="nofollow">https://www.abstractsonline.com/pp8/#!/9325/presentation/238 target="_blank" rel="nofollow">https://www.abstractsonline.com/pp8/#!/9325/presentation/238

A second https://www.abstractsonline.com/pp8/#!/9325/presentation/235 3"" target="_blank" rel="nofollow">https://www.abstractsonline.com/pp8/#!/9325/presentation/235 target="_blank" rel="nofollow">https://www.abstractsonline.com/pp8/#!/9325/presentation/235

MCT2 has been documented in multiple cancer types [1], and may compensate for inhibition of MCT1 and/or MCT4. So targeting that could help, as well as OXPHOS [2].

Refs:

1 https://www.hindawi.com/journals/bmri/2010/427694/

2 https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.35

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