Anyone used 3bp (3-bromopyruvate)?

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

by dumbcritic on Fri Oct 04, 2019 07:10 PM

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Below are some SITC titles (on the 5th of Nov the abstracts will be released at 8 a.m. EST)
(P497) DRP-104, A Novel Broad Acting Glutamine Antagonist, Induces Distinctive Immune Modulation Mechanisms and Synergistic Efficacy in Combination with Immune Checkpoint Blockade
(P501) Dietary deprivation of non-essential amino acids improves anti-PD-1 immunotherapy in murine colon cancer
(P633) BPM31510, a Metabolic Modulating Anti-Cancer Agent, Demonstrates Immune Potentiating Properties by Promoting Cytotoxic T Cells and Reversing Indices of Exhaustion and Immunosuppression
(P816) DRP-104 Induces Durable Responses In Vivo by Inhibiting Tumor Glutamine Addiction, Remodeling the Tumor Microenvironment and Stimulating Both the Innate & Adaptive Immune Systems
(P845) Targeting of Lactate Dehydrogenase C and its effects on the tumor immune microenvironment: two birds with one stone

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

by dumbcritic on Sat Oct 05, 2019 09:25 PM

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A preclinical paper that shows an FDA approved drug for the treatment of arthritis (Leflunomide) promote mitochondrial fusion in pancreatic cancer cells and extends survival time (at least in mice) [1].

Also, another which tested a molecule (Glutor) that was shown to block a number of varieties of glucose transports. The authors showed that glucose metabolism in 44 different cancer cell lines were potently inhibited by this drug (in vitro) and that in non-cancerous cell lines metabolism was not adversely affected. With added CB-839 there was synergistic inhibition [2,3].

Refs:

1 https://insight.jci.org/articles/view/126915

2 https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(19)30206-5

3 https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(19)30279-X

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

by Jcancom on Fri Oct 18, 2019 12:02 AM

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The Nobel prize in medicine has been awarded for 2019 -- that was about a month ago. I heard about the announcement within a day or so and all that I was able to process was that it was something about oxygen levels and perhaps something about HIF-alpha and that it was possibly related to cancer. It was quite vague so I went about my business.

It has only been in the last day or so that clarificaiton has emerged; Specifically that one of the three winners of this year's Medicine Nobel was a coauthor on a significant 3-BP paper (the pancreatic cancer one that used a beta-cyclodextrin formulation of 3-BP).The results using systemic cyclo-3-BP in pancreatic cancer in vivo were impressive.

We talked a great deal about this article on the thread over the last 5 years and our working guess is that Cage wants to brings this formulation to clinical trials. It is frustrating, though, that after all these years a better formulation likely could be devised, yet at some point people want to move something forward; it would probably take years more research to optimize the existing formulation. 

The relationship between the Nobel and the article is very unclear, and it will not be made any more clear for about 50 years until the deliberations are released. Nonetheless, the ongoing thread speculation that 3-BP will feature prominently on the Nobel podium appears to have already occurred. Perhaps this is a subtle nod by the Nobel committee to 3-BP. It would obviously have been interesting to have watched a 3-BP market security respond to this news, though such a 3-BP proxy is yet unlisted.     

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300523/

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

by dumbcritic on Fri Oct 18, 2019 10:41 PM

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Some early data on RP1 (an OV) in CSCC [1,2]. Here are links to the trials [3,4].

Also, a link to another trial [5]. SAR441000 is made up a mixture of mRNAs that encode for immunomodulatory cytokines (IL-12sc, IL-15sushi, IFN-a and GM-CSF). When injected into tumours, it should induce immunity to tumour-specific antigens.

Refs:

1 http://www.globenewswire.com/news-release/2019/10/15/1929577

2 https://ir.replimune.com/static-files/92ceb475-65c1-4086-a46

3 https://clinicaltrials.gov/ct2/show/NCT03767348

4 https://clinicaltrials.gov/ct2/show/NCT04050436

5 https://clinicaltrials.gov/ct2/show/NCT03871348

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

by dumbcritic on Sat Oct 19, 2019 10:51 PM

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On Oct 18, 2019 12:02 AM Jcancom wrote:

The Nobel prize in medicine has been awarded for 2019 -- that was about a month ago. I heard about the announcement within a day or so and all that I was able to process was that it was something about oxygen levels and perhaps something about HIF-alpha and that it was possibly related to cancer. It was quite vague so I went about my business.

It has only been in the last day or so that clarificaiton has emerged; Specifically that one of the three winners of this year's Medicine Nobel was a coauthor on a significant 3-BP paper (the pancreatic cancer one that used a beta-cyclodextrin formulation of 3-BP).The results using systemic cyclo-3-BP in pancreatic cancer in vivo were impressive.

We talked a great deal about this article on the thread over the last 5 years and our working guess is that Cage wants to brings this formulation to clinical trials. It is frustrating, though, that after all these years a better formulation likely could be devised, yet at some point people want to move something forward; it would probably take years more research to optimize the existing formulation. 

The relationship between the Nobel and the article is very unclear, and it will not be made any more clear for about 50 years until the deliberations are released. Nonetheless, the ongoing thread speculation that 3-BP will feature prominently on the Nobel podium appears to have already occurred. Perhaps this is a subtle nod by the Nobel committee to 3-BP. It would obviously have been interesting to have watched a 3-BP market security respond to this news, though such a 3-BP proxy is yet unlisted.     

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300523/ "" target="_blank" rel="nofollow">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300523/ " target="_blank" rel="nofollow">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300523/

Dr. Semenza was the discoverer of the hypoxia-inducible factor (HIF) proteins. He and Drs. Kaelin, Jr and Ratcliffe were awarded the prize ''for their discoveries of how cells sense and adapt to oxygen availability.'' In cancer, we know HIF-1 overexpressed in many types and promotes growth and metastasis through its role in initiating angiogenesis to overcome hypoxia [1-3].

Cage Pharma seems to be PreScience Labs [4]. As for the paper you have cited the first thing that sticks out to me is that Drs. Jean-François Geschwind and Bert Vogelstein are co-authors. We all know about the former and in my view the latter could have played a role in the past too. 

Refs:

1 https://cancerres.aacrjournals.org/content/59/22/5830.long

2 https://ajp.amjpathol.org/article/S0002-9440(10)64554-3/fulltext

3 https://link.springer.com/article/10.1007%2Fs10555-007-9055-

4 https://www.ncbi.nlm.nih.gov/pubmed/30819474

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

by dumbcritic on Thu Oct 24, 2019 07:16 PM

Quote | Reply

On Oct 18, 2019 10:41 PM dumbcritic wrote:

Some early data on RP1 (an OV) in CSCC [1,2]. Here are links to the trials [3,4].

Also, a link to another trial [5]. SAR441000 is made up a mixture of mRNAs that encode for immunomodulatory cytokines (IL-12sc, IL-15sushi, IFN-a and GM-CSF). When injected into tumours, it should induce immunity to tumour-specific antigens.

Refs:

1 http://www.globenewswire.com/news-release/2019/10/15/1929577 /0/en/Replimune-Provides-Update-on-RP1-Clinical-Development-Program-in-Cutaneous-Squamous-Cell-Carcinoma.html"" target="_blank" rel="nofollow">http://www.globenewswire.com/news-release/2019/10/15/1929577 target="_blank" rel="nofollow">http://www.globenewswire.com/news-release/2019/10/15/1929577

2 https://ir.replimune.com/static-files/92ceb475-65c1-4086-a46 1-d3087a568ffe"" target="_blank" rel="nofollow">https://ir.replimune.com/static-files/92ceb475-65c1-4086-a46 target="_blank" rel="nofollow">https://ir.replimune.com/static-files/92ceb475-65c1-4086-a46

3 https://clinicaltrials.gov/ct2/show/NCT03767348 "" target="_blank" rel="nofollow">https://clinicaltrials.gov/ct2/show/NCT03767348 " target="_blank" rel="nofollow">https://clinicaltrials.gov/ct2/show/NCT03767348

4 https://clinicaltrials.gov/ct2/show/NCT04050436 "" target="_blank" rel="nofollow">https://clinicaltrials.gov/ct2/show/NCT04050436 " target="_blank" rel="nofollow">https://clinicaltrials.gov/ct2/show/NCT04050436

5 https://clinicaltrials.gov/ct2/show/NCT03871348 "" target="_blank" rel="nofollow">https://clinicaltrials.gov/ct2/show/NCT03871348 " target="_blank" rel="nofollow">https://clinicaltrials.gov/ct2/show/NCT03871348

RP2 moves forward https://www.globenewswire.com/news-release/2019/10/24/193491

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

by dumbcritic on Thu Oct 31, 2019 01:37 AM

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I've just come across this paper from back in March. A Specific Ketogenic Diet (SKD), Ozone Therapy, HBOT, and herbal supplements were used.

"Results: After Phase (1) of this research on 54 patients the average percentage decrease in the tumors was 58% and after Phase (2) on 31 remaining cancer patients the average percentage decrease in the tumors was 98.8%.''

https://researchopenworld.com/the-positive-effect-of-skd-plu

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

by HopefulDJ on Tue Nov 05, 2019 11:53 PM

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I am a strong supporter of metabolic treatments. This article refers to some pretty dramatic results but the article seems a little sketchy to me. First they said it was controlled but there was no control. Second, they said they used HBOT but later in the article, they say that they just used a mask which delivered pure oxygen. Some of the discussion of topics like the specific ketogenic diet sound good. I am for the ability to present research in non-traditional journals but the low quality of the grammar along with several inconsistencies made me doubtful.

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

by JohnnyP on Wed Nov 06, 2019 02:15 AM

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The facility we used (Advanced Hyperbarics) provided a mask inside the chamber.  We were at 3 ATA for 90 minutes.  I breathed ambient air, my wife breathed 100% oxygen through a small face mask.

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