Anyone used 3bp (3-bromopyruvate)?

5142 Posts | Page(s): Prev 12...499 500 501 502 503 ...514515 Next 

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

by dumbcritic on Wed Feb 27, 2019 09:25 PM

Quote | Reply

On Feb 26, 2019 2:02 PM JohnnyP wrote:

They use a cocktail of four repurposed, or off label, drugs with known safety profiles.  He spoke about metformin, statins, albendazole, and doxyclycline.

The clinic they opened is in Rapid City, SD.  I think that's where Dr. Annette Bosworth is (Dr. Boz).  She has a great story of helping her Mom survive cancer, based on the ketogenic diet.

IM156 is an orally administered small molecule OXPHOS inhibitor from the biguanide class (Metformin is a biguanide as is Buformin, and Phenformin) in a clinical trial [1]. 

There is also another OXPHOS inhibitor in a trial [2].

Refs:

1 https://clinicaltrials.gov/ct2/show/NCT03272256

2 https://clinicaltrials.gov/ct2/show/NCT03291938

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

by dumbcritic on Wed Feb 27, 2019 10:50 PM

Quote | Reply

On Feb 18, 2019 1:37 AM Jcancom wrote:

Page 500!

Yeah, this is exciting! Moving toward post 5000 with vitality and confidence!

The 3-BP story line continues to advance forward and upward! I can hardly wait to see the clinical trial finally start.

critic, I came across a very interesting article that talked of how rhodamine ( I believe it was), can clear normal cells within a few hours, though this can take days for cancer cells. It has occurred to me that this might be of considerable relevance as an anti-cancer strategy. For example, one could imagine a prodrug loaded onto something such as rhodamine that might be allowed to clear normal cells and then an activating drug administered once such clearance had been accomplished in the normal cells but not the cancer cells (other combinations are also imaginable). Are you aware of any cancer therapies that use this strategy?  

No, I'm not. 

Calithera has presented some more data on CB-839 in pts with mRCC [1]. Also, NeOnc Tech will share their NEO100 (perillyl alcohol) data [2].

Refs:

http://www.calithera.com/wp-content/uploads/2019/02/ASCO-GU-

https://www.abstractsonline.com/pp8/#!/6812/presentation/987

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

by JohnnyP on Thu Feb 28, 2019 02:49 AM

Quote | Reply

Travis Christofferson wrote "Tripping Over the Truth" and told the story of Dr. Ko and 3BP.  Now that he is at the Care Oncology clinic in Rapid City, maybe we can call and ask about the status of 3BP.

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

by Jcancom on Fri Mar 01, 2019 03:10 AM

Quote | Reply

3-BP clearly has a great deal of potential and this potential continues to intensify as yet more preclinical research and more formulations are published. In the last month or so I came across another formulation, though it has still not reached pubmed.

I am especially excited about using the acetate radiotracer. If this could be used to prescreen responders to 3-BP, then it would greatly reduce the uncertainty that is often present with even clinical candidates as powerful as 3-BP. It would be a great mystery to me if patients in a 3-BP clinical trial were not screened with both FDG and acetate radiotracer.

Thank you for keeping us up to date with CB-839, critic! There are only a countable number of metabolic escape routes apart from glucose, yet it is comforting that there is a late stage product targeting glutaminase.

Neonc is also clearly very exciting. It is almost too much having to wait for more info on POH-3-BP! If they could really selectively deliver 3-BP to cancer cells without respect to MCT-1 status that would be very very startling. MCT-1 is the most obvious path of resistance that cancer cells could try. Without this defensive strategy, I am not sure what the fallback would be.   

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

by dumbcritic on Sun Mar 03, 2019 11:28 PM

Quote | Reply

On Mar 01, 2019 3:10 AM Jcancom wrote:

3-BP clearly has a great deal of potential and this potential continues to intensify as yet more preclinical research and more formulations are published. In the last month or so I came across another formulation, though it has still not reached pubmed.

I am especially excited about using the acetate radiotracer. If this could be used to prescreen responders to 3-BP, then it would greatly reduce the uncertainty that is often present with even clinical candidates as powerful as 3-BP. It would be a great mystery to me if patients in a 3-BP clinical trial were not screened with both FDG and acetate radiotracer.

Thank you for keeping us up to date with CB-839, critic! There are only a countable number of metabolic escape routes apart from glucose, yet it is comforting that there is a late stage product targeting glutaminase.

Neonc is also clearly very exciting. It is almost too much having to wait for more info on POH-3-BP! If they could really selectively deliver 3-BP to cancer cells without respect to MCT-1 status that would be very very startling. MCT-1 is the most obvious path of resistance that cancer cells could try. Without this defensive strategy, I am not sure what the fallback would be.   

NEO100 has been awarded Fast Track and Orphan Drug Status by the FDA. Cohort 3/4 is also finished in the PhI. Of the eight patients enrolled with long term follow up, three have survived more than seven months with the drug alone, and one is out 14 months. Others trials are planned in pediatric brainstem gliomas and skull base tumours. Intra-arterial delivery will be studied in those with CNS cancers. NEO218 (3-BP POH) is down the list of other drugs in their pipeline.

SM-88 will be going into a pivotal trial in those with 3L mPDAC. Some data has been presented [1]. The company is working on an injectable (digestively compromised patients), nasal (glioma) and transdermal (breast) delivery too.

Hopefully, if CB-839, SM-88, VDA-1102, Devimistat (CPI-613) and/or a few others are successful major pharma will take note and start work on their own compounds to target energy metabolism.

Ref:

1 https://s22.q4cdn.com/265040820/files/doc_downloads/scientif

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

by Jcancom on Fri Mar 08, 2019 01:42 AM

Quote | Reply

critic, thank you for the citation. It is startling how many of these metabolic protocols are being reported. My hard drive is almost jammed pack! It's endless! As I recently mentioned, my suspicion would be that as soon as 3-BP is firmly in the clinic that an entire ecosystem of metabolics will materialize. There are so many treatments that have already been found to synergize with it; I would have to think that there would be a fair number that are still waiting to be found. The article below actually suggests the identity of several of these (most prominently methylglyoxal).  

I could imagine a scenario in which a near endless list of metabolic treatments could be tried in sequence until an effective combination were unlocked. As I have noted with 3-BP, one would even have the acetate scan to determine whether the MCT-1 port were open. Once this was established, then one would prospectively know that 3-BP should be effective and it would only be a question of finding synergistic combos. The metabolic escape routes are being systematically found and closed off.

JohnnyP has also been a great help in evolving my understanding of approaches to metabolics. I had not known what to make of the caloric restriction/ketogenics idea, while it is now moving into focus for me as well. Today I came across https://www.totallyyu2.com/reference-videos-and-seminars/2-u which reports substantial success in human cancer using metabolic concepts.

Big news for 3-BP today! A review article was posted online;  not yet on pubmed.

https://www.mdpi.com/2072-6694/11/3/317#   (need to right click and select open in a new window to see the full text; double clicking the link doesn't seem to work).

Great article! Putting all the 3-BP research together in one place greatly helps to see the whole landscape. I like the way that they gradually work up the complexity of the figures until they reach Figure 5.

Do you know that they have at least 11 mechanisms of action for 3-BP? Comments that dismiss the potential for 3-BP are simply not plausible. How couldn't it work with so many shots on goal? How many does it take? The recent bioorthogonal article noted, in fact, that 3-BP affects at least 62 proteins.

The authors did a great job of summarizing 3-BP research. I don't want to be labelled a whiner, yet I was somewhat disappointed that they did not include:

PMID: 25709804  mito-3-BP! These mito formulations if proven safe could be extremely effective. Amplifying 3-BP's effectiveness 10 fold and entering cells independly of MCT-1 has to deserve a mention.
PMID:21237678  ethylbromopyruvate: would be very interested in seeing how this might be used to enhance safety. Injecting 3-BP which forms the strong acid HBr and causes injection site vein irritation is best avoided if possible. 

https://www.eacr25.org/user_uploads/files/esmoopen-2018-EACR PO-437  (pdf page 213) ultra-sound 3-BP! D's forum has a post that mentions that going to an ultra-sound formulation can boost targeted delivery by over 10 fold! This could be another major amp up for 3-BP. Perhaps even ultrasound could be applied to CP-102?
Also somewhat crushed that no mention was made of   [11C]acetate imaging. If my thinking were correct, such imaging could be of very substantial relevance for 3-BP's path through the  clinic. 

Reviews articles are tough to write because so much of the good material needs to be edited out!

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

by Jcancom on Sat Mar 09, 2019 06:13 PM

Quote | Reply

How did we miss this one? Scientific literature indeed! This article is very well written and puts a whole new spin on alkylation.

Chemists usually look at 3-BP and immediately dismiss it due to its strong alkylating features. The article notes that chemotherapeutic alkylating agents are at the top of cancer's stigma scale. wiki reports that ethyl bromoacetate was a chemical warfare agent during WW1. Ordinarily, the words "alkylating agent" by themselves could be used as a nearly unbeatable argument against treatments such as 3-BP.

Not so fast! The article explains that there is a whole new generation of selective alkylators that behave in a very non-alkylating manner. Article mentions 3 such agents: TH302 (renamed evofosfamide), RRX-001 and 3-BP.

Evosfamide with its dual bromide tails still completed phase 3 trials, although not showing strong anti-cancer effects. Its hypoxia activation mechanism might be used more broadly, possibly even with a 3-BP type analog.

RRX-001, which has a 3-BPish bromide end, is now into phase 3 and perhaps could be combined with 3-BP as it apparently targets GSH.

The article's proposed rebranding (so to speak) of promiscuous selective alkylators does serve as a powerful rebuttal to the assumption that alkylation must necessary be toxic (e.g., nitrogen mustards, other chemical warfare agents, and traditional chemotherapies). They could have the power of an alkylator without the toxicity.

Proud to be an A!

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431031/

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

by JohnnyP on Sun Mar 10, 2019 07:08 PM

Quote | Reply

Does anyone know how to view PET scan images?

I posted the question on a google group:

https://groups.google.com/forum/#!topic/comp.protocols.dicom

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

by JohnnyP on Sun Mar 10, 2019 08:23 PM

Quote | Reply

I found an online viewer:

https://www.dicomlibrary.com/

I see activity, but don't have the images from her first two PET scans to compare, so I don't know if it's better or worse.

We'll have to wait for the report and the consult.

5142 Posts | Page(s): Prev 12...499 500 501 502 503 ...514515 Next 
Subscribe to this message board discussion

Latest Messages

View More

We care about your feedback. Let us know how we can improve your CancerCompass experience.