Anyone used 3bp (3-bromopyruvate)?

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

by dumbcritic on Thu Jun 20, 2019 04:10 PM

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NeOnc Technologies, PhI trial is fully enrolled and is progressing with encouraging results.

Cohort 1: 96 mg/dose 4 times a day (384 mg/day total)

Cohort 2: 144 mg/dose 4 times a day (576 mg/day total)

Cohort 3: 192 mg/dose 4 times a day (768 mg/day total)

Cohort 4: 288 mg/dose 4 times a day (1152 mg/day total)

Key results

• 1. NEO100 has induced a radiographic reduction in size in recurrent GBM in a dose-dependent manner in several patients

• 2. NEO100: very well tolerated

• no significant adverse effects

• 3. Patients tolerate treatment regimen very well (compliance by patient log and self-reporting)

{Regimen is a 4x/day for 28 days}

• 4. Higher doses of NEO100 result in a higher response in patients over six months

• Cohort 1 – no response (0/3)

• Cohort 2 – 33% response (1/3)

• Cohort 3 – 67% response (2/3) – one has a complete radiographic response

• Cohort 4 - underway

Individual Cohort Results – note results between cohorts vary because dose escalated from cohort to cohort for toxicity assessment and improved therapeutic outcome evidenced with higher dose cohorts.

Cohort 1, Phase I

• 1. No significant adverse effects

• 2. All patients had a progression of tumor size after two months.

• 3. MRI scans from two of the patients demonstrated a change from solid to cystic tumor

• 4. 0 % response rate

• Two of the patients had repeat surgery

• A change in characteristics of the tumor,

• A decrease in Ki-67 for both tumors

Cohort 2, Phase 1

• 1. First patient-progressed after two months

• 2. Second patient-2 years of treatment

• still alive

• no seizures (prior to treatment 2-3 seizures per week, mostly partial but some generalized)

• tumor smaller on MRI

• the patient is continuing on therapy

• 3. Third patient-progressed after four months

• 4. 33% response rate after six months

Cohort 3, Phase 1

• 1. Cleveland Clinic-1 patient-one year out

• complete response

• 2. USC-1 patient –one year out

• no progression

• reduction in tumor size

• 3. USC 1 patient-3 months out-stable

• 4. 67% response rate over six months

Results-Cohort 4, Phase 1

• Three patients recruited

• Two at one month of treatment

• One just started treatment

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

by Jcancom on Fri Jun 21, 2019 03:14 AM

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JohnnyP, it is such a joy to share in your successes! You are doing such a great job.There is an overwhelmingly large research base that can make cancer seem almost unknowable. That you have been able to extract the knowledge that you needed to help your wife inspires hope.

I would tend to want to press forward, even in light of this good news, though it is often better not to exchange a known success for an uncertain utopia.

You do not have to go far back on this thread to find that we had years and years in which nothing seemed to help our friends very much. Now it feels like success is everywhere!

I greatly wish that others who might be struggling with cancer will find our journey's chronicle helpful. They could skip past all our wrong turns and head out in the right direction from the beginning. 

While we are still in an exploratory stage (with many people making their own trail), the connecting commonality is anti-metabolics. You are trying out one metaobolic variant, there are now so many to even list. We have wanted to get going on a glycolytic list on D's forum for quite some time, though my list kept getting longer and longer. Too much information? It is startling how much potential is still in uncharted territory in metabolics.

Very glad to hear the good news! Best Wishes, Jcancom

 

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

by Jcancom on Fri Jun 21, 2019 03:55 AM

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critic, Wow! More great news! It's everywhere.

Pushing to over 1,000 mg daily intranasal dosing of POH! That is an extremely large dose considering the route of administration. With all that therapeutic index slack sitting there on the table, I am very interested to see what will happen when they go POH-3-BP intranasal. 

Downdosing: I would tend to think that 1,000 mg of POH-3-BP intranasal would be well beyond what would be needed clinically. the POH family might offer us a very clean entry route into the brain. 

Response: If POH can give us good targeting of 3-BP, then it should not be unreasonable to see substantial responses. 4 times daily dosing gives a metronomic feel which we have seen can be a powerful anti-cancer approach especially in the metabolic universe.

The big question outstanding for me is how POH-3-BP can sidestep MCT-1. It would be a massive development if that could be more fully explained. If POH can truly target cancer cells independently of MCT-1, then there would not seem to be an obvious final line of defence for cancer. Cancer cells can and do shut down MCT-1, though when 3-BP is able to enter cancer cells, there is almost no chance for the cancer to resist: 3-BP attacks almost everything within the cell. We will want to see more research establishing that this targeting is cancer selective.

Pubmed has a fair amount of research published over the last few months in which the next generation of POH compounds are highlighted. They were shown to further amplify the POH effect.       

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

by Jcancom on Fri Jun 28, 2019 12:06 AM

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

by dumbcritic on Tue Jul 02, 2019 03:55 PM

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Calithera Bio have initiated a PhI/II trial of Telaglenastat (CB-839) in combination with Pfizer's CDK4/6i Palbociclib. 

Also, MetVital will test AEO (Anhydrous Enol-Oxaloacetate) in patients with GBM. The PhIIa trial endpoints are six month PFS, OS and number of seizure events.

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

by dumbcritic on Fri Jul 05, 2019 11:50 PM

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On Jun 21, 2019 3:55 AM Jcancom wrote:

critic, Wow! More great news! It's everywhere.

Pushing to over 1,000 mg daily intranasal dosing of POH! That is an extremely large dose considering the route of administration. With all that therapeutic index slack sitting there on the table, I am very interested to see what will happen when they go POH-3-BP intranasal. 

Downdosing: I would tend to think that 1,000 mg of POH-3-BP intranasal would be well beyond what would be needed clinically. the POH family might offer us a very clean entry route into the brain. 

Response: If POH can give us good targeting of 3-BP, then it should not be unreasonable to see substantial responses. 4 times daily dosing gives a metronomic feel which we have seen can be a powerful anti-cancer approach especially in the metabolic universe.

The big question outstanding for me is how POH-3-BP can sidestep MCT-1. It would be a massive development if that could be more fully explained. If POH can truly target cancer cells independently of MCT-1, then there would not seem to be an obvious final line of defence for cancer. Cancer cells can and do shut down MCT-1, though when 3-BP is able to enter cancer cells, there is almost no chance for the cancer to resist: 3-BP attacks almost everything within the cell. We will want to see more research establishing that this targeting is cancer selective.

Pubmed has a fair amount of research published over the last few months in which the next generation of POH compounds are highlighted. They were shown to further amplify the POH effect.       

Cohort 4 is the last in the dose escalation. Whatever is the maximum tolerated dose will then be moved forward in a PhIIa which will enroll 25 patients. I assume (rightly or wrongly) they will take the 1152 mg dose forward. If so, we could get some early data on this at AACR or ASCO next year.

If the data is encouraging, I hope the company are able to raise money. The reason why is the last funding type was 'seed' back in 2012 [1].

Moving on to NEO218 (POH-3-BP) it is hard to know when a PhI trial could start. I also agree with you that 1,000 mg of the drug is unlikely needed to show activity.

As for how it enters cells in an MCT-1 independent manner it is possible that there are interactions with the lipid bilayer [2] or it could be via another transporter. Hopefully, the company and/or another group will do more research on this.

Refs:

1 https://www.sec.gov/Archives/edgar/data/1478689/000147868912

2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722523/

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

by JohnnyP on Mon Jul 08, 2019 12:43 PM

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Shirley's CA15-3 marker has been rising about 10 counts per month, latest reading is 87.5.  High normal is 25.  Not a scary number yet, and it hasn't gone exponential, but I want to slow or reverse it.  I've been reading Jane McClelland's book and want to add two drugs she used, Lovastatin, and Dipyridamole.

The statin deprives the cancer of cholesterol used to make the cell membrane, and the Dipyridamole prevents platelets clumping, hindering passage of cancer stem cells through capillaries, where they could implant and metasasize.

McClelland says NSAIFD increases the effect of the statin 5x.  She was taking Etodolac with the statin, Shirley is already taking the NSAIFD Meloxicam.

Metformin is another that she recommends, which we are already getting.

I presented some information on these to the oncologist's P.A. last week, asking for prescriptions.  She said she would have to ask her boss.

I showed her McClelland's book, and Seyfried's famous book, "Cancer as a Metabolic Disease".  She hadn't heard of it.  She said she uses what she called "the bible", a much bigger book than what I showed her (my book is begger than your book).  She went on to say (referring to my prescription request), "If these work, why aren't they being used?"

I told her we are also doing low carb/keto, less than 20g/day.  She said, "Oh, I'm not sure I like that.  I'm diabetic and have to limit carbs to less than 160g/day."  God help her patients.

We are continuing with HBOT, and have increased the time from sixty to ninety minutes at three atmospheres.

She was diagnosed 14 months ago.  Clinically, she is doing really well, and is able to do a little more each day.  Her appetite is improving, and her weight has been stable at 140 for the last three weeks.

The survival curve shows half the women in a study die within 18 months of diagnosis of metastasis.  Refer to table 1, here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289136/

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

by Jcancom on Tue Jul 09, 2019 02:35 AM

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JohnnyP, thank you for updating us! Of all the suggestions that I might give to you, remaining engaged with research into alternative treatment approaches would be at the top of the list, and I am very glad to see that you have remained so engaged. There are such an extraordinary number of treatment possibilities out there; you should never think that there is nothing left to try. I had not been aware of the combo that you mentioned, though it is comforting to know that you continue to seek out these new treatments.

Magnetic hypetthermia, FB combos, silver nanoparticles and many others have recently captured my attention. There is a bubbling sense of optimisim. {Perhaps consider the FB + DCA or FB + 2-DG combos; the combination indices for them were starting! 0? Super-synergy?} . With magnetic hyperthermia, within the last two weeks an article was published that detailed how systemic delivery along with low force magnetic fields could have in vivo anti-cancer effects. It is endlessly exciting how much high quality research is constantly being published. 

Yes, the argumentation that we are up against falls short of even qualifying as specious; it is rhetorically hollow. How many million women died of breast cancer because of the application of standard of care medicine when it should have reasonably been anticipated that this standard would have been found to be ineffectual and this plausibly could have been anticipated perhaps decades ago (TailorX study)? This is the scale of catastrophe that can emerge when an organized medical system standardizes care to a treatment protocol that is at least discovered to be not scientifically valid. For whatever reason, we have allowed non-rational arguments to displace rational ones, even when the negative consequences can be severe.

I continue to wonder about the 0 carb diet approach. I had not been aware that carbs are not an essential nutrient. Modern diets are typically filled with carbs (as you noted), though appently we can live without them. With cancer especially, lactate can be recycled to glucose. Might cancer patients draw down their lactate in this way? One would imagine that this might be of considerable help. Lactate causes such a great number of problems associated with cancer. Very interested to read about quantified cancer patients who might have tried this idea.  

JohnnyP, don't let the average be your goal! Your understanding and dedication have been obvious right from your first post on the forum. You are above average! The journey that you are on and the discoveries that you make, can light the path for all those that will follow you.

We are now seeing a remarkable feedback mechanism on D's forum in which all of these journeys by all of our friends are achieving exactly this result. We have made a few steps in the right direction, I am still waiting for the time in whcih there is a lift-off moment.

I am going to reach again to try and find the truth; what I can see happening is that there is an emergent property in which a broad movement people with a tremendous dedication to ending cancer are converging on sites such as D's and they appear capable of transferring their wisdom and sustaining positive feedback. One never knows when another step forward will be made.         

Very glad to hear of your successes,                             Best Wishes Jcancom

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

by Jcancom on Wed Jul 10, 2019 02:18 AM

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critic, I reread the POH-3-BP article from 2017. It is simply stunning. There is no resistance! Everyone, Read the article, it's massive.

If you have guaranteed unrestricted access to the interior of cancer cells, selectively, with a drug in the 3-BP universe that is pretty much game over as far as I see it. 3-BP attacks everything inside the cell: it's not pretty; some would like a more scientifically satisfying treatment, though getting the job done should be the de facto standard for evaluations purposes for now over earning style points. This is still in vitro, so early days, but it is still an eye opener. 

With 3-BP, cell viability might be brought down to 10% and then a resistant colony emerges without MCT-1 expression; 3-BP is then mostly ineffective (as per the article). With POH-3-BP, cell viability went straight down and hit ZERO. There is no resistance because MCT-1 is not even needed. All the cell lines had very similar susceptiability to POH-3BP.

We really need to see more of this one. 2 years is too long for something this good.

We have had posters on thread with brain cancer and it is always terrifying to think of what they are going through. People of conscience are morally obligated to advocate to the extent of their understanding on behave of those unable to do so effectively for themselves. Considering the broad treatment success that has already been demostrated for the POH drug class in brain cancer in Brazil, it would not seem unreasonable to accelerate development of these drugs.    

One misspeak I made earlier was that the 2017 said nothing about intranasal dosing. Some of the others in the POH-combo class actually will not be dosed intranasally.  Yes, 1,000 mg POH-3BP intranasally would be an enormous and improbable dose. The rule of thumb that we know is that when you move down to microgram scale systemic dosing you are moving to scary powerful cancer drugs. POH-3-BP might be one of these.

One aspect of this that interested me was that there is always the issue of the BBB. I wondered what might happen if they intranasally dosed and the drug was locked into the brain side of the BBB. If this were to be true with POH-3-BP or other POH drugs, perhaps having a BBB opening treatment would be helpful to have on standby.  

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