Skip to main content


3-Bromopyruvate: What a Mess

There have been several reports of the use of 3-bromopyruvate as an anticancer therapy, despite (as far as I can see) a lack of any controlled human data. People occasionally bring it up in the comments here, but I’ve never written on it myself. The literature has a number of papers on its effects in cells and organisms like yeast (those are all very recent papers, and the references therein will take you to many more). The compound appears to disrupt glycolysis (as well it might) and is thus suspected to be a Warburg-effect play against tumor cell metabolism (although there could certainly be other things going on as well).

That’s not at all a crazy idea – there’s been a lot of work on the Warburg effect, and it remains a viable approach to at least some forms of cancer (although the enthusiasm in this area is definitely not what it was a few years ago). 3-bromopyruvate would seem to be a fairly vicious molecule to give a person, but that’s by the standards of regular small molecules, not by the standards of chemotherapy. (At the very least, it looks as if it would strip out your glutathione pretty handily). So overall, this looks like something that really needs some good clinical data behind it, because it might well be useful, at least in some cases.

Unfortunately, the situation has been clouded by use of 3-BP by all sorts of “cancer clinics” that cater to the desperate, so long as they have the cash. And now it seems that one of these in Germany has had three patients suddenly die after receiving the compound – here’s an article at Science on the case, and a detailed look at it (and at 3-BP) at the Science-Based Medicine blog. I should note, though, that the Science article refers to 3-BP as “part of a class of compounds known as small molecule drugs”, which is one of the least informative descriptions I’ve come across in a while. I’m not trying to bite the hand that hosts me here, but that’s a bit like referring to a Honda Civic as one of the class of four-wheeled vehicles known as automobiles.

Otherwise, though, that article is a good overview of the situation, and the Science-Based Medicine post adds even more detail. It would appear that the original report of the compound’s clinical use was, in fact, more complicated than people tend to realize, and the efficacy ascribed to 3-BP by it could well have been oversold. But that’s what further clinical work should be able to sort out (as well as sorting out other questions such as dosing protocols, which would be very important with a reactive compound like this). The proposed clinical trial apparently has no funding to go forward, though, and there appears to be legal disputes about its use, going back to the original researchers at Johns Hopkins, according to the S-B M blog post. A lawsuit was filed several years back by one of the people involved, and both they and others have filed competing patent applications, which cannot be speeding things up much.

That doesn’t stop multitudes of cancer-cure people from claiming that it’s all a conspiracy by Big Pharma to keep the miracle cure off the market. But what’s happening instead is that a potentially useful compound – not a broad-spectrum cure, by any means – is now in such a mess, thanks partly to its original proponents and partly to the alternative cancer cure folks, that it’s going to be harder than ever for anyone to find out what it can really do.

44 comments on “3-Bromopyruvate: What a Mess”

  1. cirby says:

    Fake cancer cures are eternal.

    A young friend of mine was touting the “amazing Vitamin B-17 cure” a while back, complaining because the FDA wouldn’t let people sell it in the US.

    “You mean laetrile?”

    “No, it’s a vitamin. Perfectly natural.”

    “It’s laetrile. It’s a fraud. People die because of it.”

    “But it’s a VITAMIN!”

    1. Christopher Bruno says:

      This is the kid that got the 3 bromo pyruvate for liver cancer taking at Johns Hopkins U.

  2. Anon says:

    “So overall, this looks like something that really needs some good clinical data behind it, … And now it seems that one of these in Germany has had three patients suddenly die after receiving the compound.”

    Looks like you answered your own question!

    1. b says:

      C’mon now. Dose response. Who knows how much he was giving these people.

      1. loupgarous says:

        Who knows, in the absence of a safety study in humans for 3-BP, what the safe dose is?

        The cancer quacks all treat FDA’s old fogey-ish insistence on animal model studies, then human safety studies in volunteers, then efficacy studies in patients as a “conspiracy.” I’ve seen FDA administrators at Drug Information Association confabs, and nobody was tucked away in a corner whispering about how to suppress goat glands, laetrile, “chelation therapy,” DCA, 3-BP or anything else. The only thing close to a conspiracy there was whispers about how good the Philly cheese steak sandwiches were in the hotel’s basement cafe.

        1. Have your tried 78% survival rate, Poly MVA IV protocol?

    2. Anon-two says:

      The German department of justice is researching 70 deaths under patients of this private clinic. The ball got rolling after three died in one week. Speculation is that the head quack of the clinic made an error and overdoses three people.

    3. Christopher Bruno says:

      Apparently what was used came from a new supplier, based here in the USA. They are investigating this to see if it was a) the supplier or b) dosage amount.

  3. simpl says:

    The Science report suggests that a practitioner considers systemic infusions to be definitely wrong. However, that is a standard means of administration, which e.g. local tumor injection isn’t.
    A slip between Freud and the printer reads“Creativity in therapy must not negatively affect patent safety,” If it is not patentable, the only way to make money would be to withhold useful details, and let the next pioneer make his own mistakes.

    1. loupgarous says:

      simpl, TACE (Trans Arterial Chemo Embolization) is actually a recognized method of treating cancerous tumors and has been for years. The technique is to advance a transluminal catheter up a major artery (the femoral seems the most popular due to ease of access and its size) through the aorta, then into the artery perfusing the tumor. There, chemotherapy drugs are injected directly into the tumor, then the artery’s embolized (stopping further blood flow to the tumor.

      There’s still some systemic spread of the chemo agents from the injection site, and with it, some systemic toxicity and side effects, but nowhere near as pronounced as with systemic chemotherapy. I can speak with a little authority on this, I just had TACE done to me three weeks ago to treat inoperable metastatic tumors in my liver. It seems to be working well.

      1. anon says:

        Sorry to hear of your situation loupgarous.

        Was your TACE with 3-BP? The original published liver patient had TACE 3-BP. Other patients online have reported positive results with it as well.

        1. loupgarous says:

          Nope. Just mitomycin and daunorubicin. I’d have volunteered for a clinical study of 3-BP, if it were delivered locally, but the old standards seem to be working well.

          1. anon says:

            I am interested in your reasoning about choosing the standard chemo TACE over 3-BP.

            You mentioned that if 3-BP were available within a clinical trial setting, then you would be interested. Do you see any possible advantages of using 3-BP over regular chemo?

            The research is fairly thin, though do you perceive that there might be efficacy differences? If clinical trials are delayed indefinitely while clinics of varying degrees of repute continue to accumulate “data”, then hypothetically would there ever be a point in which you might be persuaded merely by anecdotes and attempt 3-BP?

          2. loupgarous says:

            @anon, I ought to have been clearer. I would be interested in 3-BP IF it had cleared animal studies, and passed healthy volunteer safety tests (which I cannot realistically imagine being conducted, owing to its cytotoxicity). Then, after I’d had a chance to study the findings of an Institutional Review Board (and examined the qualifications and independence of that IRB’s members), I’d take a chance in 3-BP – if the Warburg Effect hypothesis had been validated to my satisfaction in animal models and 3-BP had been shown usable in healthy volunteers.

            Does that answer your question? I have no objection to taking part in clinical research as a subject, I’ve done it before. And if I have a recurrence of my cancer and the judgment of my oncologists is that the agents already used on me weren’t going to work well again, then I would look a t 3=BP if a properly conducted clinical trial were available.

            Not one of these “clinical trials” conducted by a guy who “voluntarily agreed not to practice medicine” where he used to practice.

          3. Christopher Bruno says:

            I would be interested in 3-BP IF it had cleared animal studies,

            According to the Doctor I spoke with at Hopkins, it has cured every tumor in every animal we tested it on. The only human used in the study was a dutch boy with liver cancer. He lived for another 2 years. This has been used on other humans, GreenSpring clinic in I think Arizona has also posted some results.
            Hands down this would be my first choice before chemo.
            Best of luck to you.

          4. David Segal says:

            Above, Christopher Bruno mentions the Greenspring Clinic. That should be the Dayspring Cancer Clinic in Scottsdale Arizona. (

  4. anon says:

    Disclosure: I have a long standing curiosity about 3-Bromopyruavte and have posted about it for quite some time. I might not be objective about 3-BP as I would like.

    Could someone on the blog help me with the comments on SBM about LDH and cancer. The bloggers maintained that the large moves in the melanoma patient from 2014 should not be overinterpreted as LDH is an indirect tumor biomarker. The patients LDH went from 4500 to 12! Most articles about 3-BP dismiss this huge LDH move without acknowledging its potential importance. One needs to carefully read the article to recognize how much the LDH actually decreased. The best SBM could do was think up idiopathic thrombotic thrombocytopenic purpura- incidence 4 in a million.

    Comment please!

    1. Me says:

      Exactly as stated: tumour volume is the readout of choice. There are plenty of drugs with rock-solid MOA that reduce levels of the biomarker but leave the tumours intact. These generally get filed under the ‘life’s a b*tch’ category. Look at amyloid in Alzheimers disease.

      Other issues, such as tissue penetration come into play also: the drug may be lowering LDH, but not in the tumour itself? the compound may be too reactive to actually hang around in enough quantities to do what it’s meant to do. The lowering in LDH levels may be downstream of some other effect…… excuses aren’t needed. If the drug doesn’t work, it doesn’t work.

    2. Mol Biologist says:

      Elements such as chlorine, fluorine and iodine are the principal antagonists of bromine.
      When you change Chlorine, 17Cl to Bromine 35Br you’re playing with Fire!
      When you are changing Chlorine, 17Cl to fluorine, 9F as it was done for GNF6702 (from Derek previous post) you are updating chloroquine vs mefloquine.
      There is often an interplay when LDH level changes in serum vs tissue (tumor). Obligate parasite P. falciparum is using same strategy during infection and PLHD level arises but not host one.

  5. anonymous says:

    I’d like to help prepare the involuntary manslaughter defense. “I did not kill those people with 3BP. I am a fraud, you know! I tried to buy 3BP from a website in China but it was too expensive so I injected the patients with saline and charged them $11,000 anyway.”

  6. anon says:

    Patients have been treated with 3-BP at various clinics over the last year or two without reported incidents. The Bracht clinic had treated the same patients without incident for two days prior. Reports indicate that the day of the incident a new batch of chemicals arrived. It has also been reported that the dosing might have been outside of the suggested safe range.

    1. Different Anon says:

      “It has also been reported that the dosing might have been outside of the suggested safe range.”

      Ya think?

      1. anon says:

        Yes, that phrasing was somewhat confusing.
        “outside the dosing guidelines”?

        If this were true, then what are we discussing?
        Approved drugs are also dangerous when dosed “outside of their
        dosing guidelines” ?

        Is the topic of discussion: The danger of treating with too much medicine?

        1. loupgarous says:

          Anon, the issue is that there are no real “dosing guidelines” for 3-BP, for the very good reason that there’s never been a formal human safety study for that drug. Ross appears to have been using it as a systemic chemotherapy agent, but with no qualifications as an oncologist or pharmacologist, and no oversight by an institutional review board. He seems to have been a thoroughgoing charlatan who killed three people out of callous greed.

          I did due diligence before undergoing every treatment for my cancer – and that included a clinical trial of lutetium-177 octreotate as a systemic agent. And before I agreed to have two potent cytotoxic agents in the same room with me, much less put in my body, I did my homework. And I cursed myself the first week afterward, when those little guys decided to show me just what they could do to my digestion and general health, but before therapy I could almost set my clock by the regularity of my liver pain. It’s gone now. I’ll wait till follow-up imaging before I have a formal celebration, but I’m a happy guy, summer colds from depressed bone marrow function and all.

    2. Harold1966 says:

      I follow this case in the newspapers and online news outlets very closely, but haven’t read anywhere that an official person or witness said that ‘the dosing might have been outside of the suggested safe range.”
      It is very likely it was, but until now, nobody said so.
      Klaus Roß, who had zero medical training, also mixed several different alt solutions in a days treatment. Clients were on drip feeds up to 6 or 7 hours, being fed different bags. He claimed to be able, again, without any medical training, to tailor treatment for each patient.
      He advertised with MMS, 2DG, DCA etc.
      One witness said that Klaus Roß did call the provider of the 3BP (factory or pharmacy that isn’t clear, yet) whom told him all was fine.
      Apparently it was not.

      1. anon says:

        An online forum rumor has reported that a former patient of the clinic received dosing beyond that which has been typically recommended.

  7. SedatedFMS says:

    To me it just looks like a gluthathione scavenger.

  8. anonymous says:

    Anything goes! How about that dichloroacetic acid for cancer cells? My opinion is that wide publicity that goes along with it gives a false hope to many cancer patients! A sort of cruel hoax.

    1. Me says:

      Looked at DCA awhile back for a friend – similar idea methinks.

  9. loupgarous says:

    I have to admit, “small molecule drugs” therapy is a scary prospect. Hydrocyanic acid? That’s pretty small, and it’s the active group in amygdalin/laetrile – not to mention the cause of all the fatalities associated with that quack nostrum.

    Being less flippant, Tecfidera (dimethyl fumarate) does seem to help relapsing multiple sclerosis patients and is the smallest molecule studied in the treatment of that disease.
    The emphasis ought to be on studied. Biogen, the people who sell dimethyl fumarate for relapsing MS, are doing it right, with proper safety and efficacy studies as provided by law (and common sense).

    Honestly, if study funding can be found for a drug previously banned in the EU as an anti-fungal (it caused allergic skin reactions, and there seems to be a sensitivity reaction in some people taking it orally for relapsing MS), then what’s the hold-up for 3-BP?

    I’d say that 3-BP was the victim of its own promoters wishing to short-circuit the whole process in place to protect patients from bad drug side-effects and being treated with a drug that doesn’t work well, when they can be getting one that does.

    Venture capitalists and the more adventurous pharmaceutical firms are going to look askance at Ross’s three deaths with 3-BP (although if press reports are true, he would have deaths had he been playing the same games with cisplatin, mitomycin, daunorubicin, or any other potent cytotoxic agent). Ross picked his patients’ pockets while doing great damage to the prospects of 3-BP ever being studied properly for the cancers that nothing’s working well for.

  10. dystopias says:

    True – the 3-BP story is a mess, but it’s also instructive.

    Targeting cancer exhibiting the Warburg effect (skewed cellular energy metabolism and proliferation, dependent on increased glycolysis) is a sound strategy the could offer potential for broad-spectrum anti-cancer agents. The question remains how to target dysregulated cancer metabolism.

    Clearly 3-BP is an indiscriminate alkylating agent, but specificity is gained via active transport due to overexpression of mono-carboxylate transporter 1 (SLC16A1) in cancer cells exhibiting the Warburg effect. Obviously, there was never any optimization work done around 3-BP – it’s simply another example of biologists finding a (commodity) tool compound with anti-cancer activity, who assessed MoA and therapeutic potential. Preclinical studies also suggested better therapeutic windows than much more sophisticated compounds (Gleevec). Things became fubarred when Johns Hopkins medical school administrators and officers made a power play to control the scientific findings, rather than helping scientists translate and develop the MoA of 3-BP into a more optimized therapeutic – that poisoned the water and damaged careers. This also messed up the clinical saga of 3-BP, compromising better preclinical and clinical studies.

    Another consideration is since there’s no composition-of-matter IP around 3-BP and its kin, a biotech or pharma may be hesitant to support/partner. However, it seems like there’s an opportunity here to invent and develop an optimized “Warburg effect inhibitor” that operates via the same general MoA as 3-BP.

    1. Mol Biology says:

      “Warburg effect inhibitor” that operates via the same general MoA as 3-BP required more understanding of mol biology what is dysregulated metabolism. IMO 3-BP may act acutely through systemic mechanism by stopping delivery of nutrients to tumor (why dosage is so important) or it can stop the tumor growth locally or may be both. In case of dysregulated metabolism it was settled for for months or may be years so you need significant time and efforts to reverse it and it would be absolutely different strategy. To manage situation by application of small molecules of by proteins/ABs in favor of the host (tumor vs host) or (obligate parasite vs host) you have to:
      1. stop growth tumor/parasite.
      2. reverse dysregulated metabolism.

    2. Brian says:

      Given Ben Cravatt’s findings that some alkylating agents are surprisingly specific in what they react with, it is entirely possible that a significantly better compound than 3-BP could be found. The key is that somebody or some group who know(s) a bit about both chemistry and the appropriate assays have to put in the work to generate the data.

      1. dystopias says:

        It would be interesting to do proteomics studies to see what’s differentially alkylated by 3-BP – i.e. normal cell line metabolism vs. cancer cell line exhibiting Warburg-effect metabolism. To my knowledge, this hasn’t been done. Such experiments could offer valuable clues about 3-BP MoA, as well as the key molecular targets/pathways associated with the Warburg-effect. In tandem, metabolomics studies could be done to complement proteomics analysis, using isotopically labeled glucose – i.e. differential glycolysis products in the absence/presence of 3-BP. With this kind of information in hand it could be possible to develop cleaner and better targeted Warburg-effect inhibitors.

  11. anonymous says:

    Acetaminophen kills over 400 HEALTHY people a year in the US. Seems there should be a low hurdle for testing oncology drugs, particularly those that are off patent like bromopyruvate. If only our government was more competent…

    1. Me says:

      Number of deaths vs number of dispensed doses?

      Water kills significantly more than paracetamol.

      1. Dihydrogen Oxide Kills says:

        Especially when administered by inhalation.

  12. Lordrobot says:

    I think you miss the point. Stage 4 is simply lethal. Cancer cells elect proliferation over other metabolic outcomes and are similar in this to cell attending to wound care. To proliferate the cancer cells sacrifices ATP in the krebs cycle for anaerobic metabolism in order to draw in more carbon for cellular division. That’s Walburg period. When cancer cells are place under stress for ATP the focus is on pyruvate and Lactic acid. Lactic Acid Dehydrogenase can block this causing apoptosis.
    3brp has been around a long time. It is essentially a pyruvate marker. H. P. Meloche, Biochem. Biophys. Res. Commun., 18,
    277 (1965).

    These patients died most likely of Lactic Acidosis. They may have been using Metformin at the same time.

    The world is not going to wait for FDA approvals. Bank on it. A perfect example at present is the sputnik of CRISPR flying over the USA from China. George Bush did plenty of damage to your nation in regard to stem cells research. Cancer Stem Cells are what are making stage 4 cancers outcomes bleak.

    I am of the school that we need to be focusing on RNAi and genetic lethals. Hitting this LDH pathway and exploiting the cancer cells need for carbon at the expense of energy production has a very high yield potential. Wasting time on focused EMT is mathematically improbable and I am being very generous. It is much closer to very highly unlikely. Need I remind you that Walburg made his finding in the 1920’s.

    The only thing I can compare this to is NASA. Three years after private companies got into the rocket business, The new firms were able to land their rockets in reverse exactly on the launch pad. NASA was never able to accomplish this. All this proves is that if you pack enough bureaucrats into any government system idiots float to the top.

    1. Lordrobot says:

      3BP is a closely related structure to lactate and pyruvate and may antagonize their effects. Pyruvate exerted a potent H(2)O(2) scavenging effect to exogenous H(2)O(2), while lactate had no scavenging effect. 3BP induced H(2)O(2) production. Pyruvate protected against H(2)O(2)-induced C6 glioma cell death, 3BP-induced C6 glioma cell death but not against DAO/D-serine-induced cell death, while lactate had no protecting effect. Lactate and pyruvate protected against 3BP-induced C6 glioma cell death and energy depletion which were overcome with higher doses of 3BP.

      This has tremendous potential.

  13. Ann says:

    Hi, I’m not a scientist so a lot of the biochemical points made here are a little over my head. However, my understanding is that a ketogenic diet would bring about the Warburg effect by interfering with ATP? As someone with stage 4 metastatic melanoma I would value your opinion.

Comments are closed.