Hello solars,
I had intended to leave out any sites with MSDS info, and the uses of
3-bromopyruvic acid for cancer, even the fascinating and potentially
thrilling inta-arterial use for cancer, but some mention is made in my
answer, as it was interwoven with other information. There is simply
very little online about this compound, and most of the information is
repeated across many sites. I have included links to most of the
relevant sites I found, in an exhaustive search. If this answer is not
what you were seeking, please let me know via an Answer Clarification,
before rating, and I will search further for you.
3-bromopyruvic acid (3-BrPA)is an alkylating agent. Alkylating agents
cause DNA stands to lose their coiling ability, effectively stopping
cell reproduction. From the limited amount of information available, I
have found that 3-bromopyruvic acid and 3-bromopyruvate are one and
the same, with pyruvate being the buffered version.
?Pyruvate (the buffered form of pyruvic acid) is created in the body
during the metabolism of carbohydrates and protein.?
http://www.truewoman.org/Notes/2903001.html
Chemical naming conventions:
?All negative ions (anions) end in ?-ide?, ?-ate?, or ?-ite?. These
contain several oxygen atoms. Hydrate simply means water molecules
have been added. Acids are ionic formulas in which the positive ion is
H+.
http://sphs.spusd.net/science/gcch07sc.pdf
The ending -ic is used only for neutral acids that contain oxygen and
do not contain a metal.
-ic acids are derived from the -ate polyatomic anions
http://www.uark.edu/depts/anylchem/if_chemed/Suffix4.html
?An anion formed by the loss of the hydrogen atom as a hydron from the
chalcogen atom of an acid characteristic group or functional parent
compound is named by replacing the "-ic acid" or "-ous acid" ending of
the acid name by "-ate", or "-ote", respectively.?
http://www.acdlabs.com/iupac/nomenclature/93/r93_592.htm
This MSDS states that 3-bromopyruvic acid and 3-bromopyruvate are synonyms.
https://fscimage.fishersci.com/msds/89939.htm
?Pyruvate (also known as pyruvic acid) occurs naturally in the body
and is an end product of the metabolism of sugar or starch?
http://www.diet-and-health.net/Supplements/Pyruvate.html
?Pyruvic acid/pyruvate - End product of the glycolytic pathway;
three-carbon metabolite that in aerobic conditions becomes acetyl Co-A
and enters the Kreb's cycle, or, under anaerobic conditions will
become lactic acid.
http://www.sncdirect.com/snc.nsf/0e731ea16028beed80256acc001f8ea7/c38f4d46032a992280256bb20050455f!OpenDocument
http://dbhs.wvusd.k12.ca.us/webdocs/Nomenclature/Acid-Nomenclature.html
3-bromo-pyruvate is a potent inhibitor of cell ATP production
http://www.biomedcentral.com/news/20020722/03/
You can see the molecular structure of 3-bromo-pyruvate here:
http://www.shigematsu-bio.com/J/supplier/epsilon/chemical/
?But Peter L. Pedersen and coworkers at Johns Hopkins School of
Medicine showed that the alkylating agent 3-bromopyruvic acid fights
liver cancer in animals with good specificity and low toxicity [Cancer
Res., 62, 3909 (2002); C&EN, July 15, page 30].?
http://pubs.acs.org/cen/coverstory/8050/8050chemhighlights3.html
You can read the entire article here, but it requires a paid subscription.
http://pubs.acs.org/emeta/AcsLogin?url=%2Fisubscribe%2Fjournals%2Fcen%2F80%2Fi28%2Fhtml%2F8028scic.html&mode=login
?The potent chemical drains cells of their energy in two ways: by
greatly suppressing their ability to use glucose for fuel; and by
hindering the ability of internal power plants called mitochondria to
make the energy molecule adenosine triphosphate, or ATP.?
http://www.daytondailynews.com/health/content/shared-auto/healthnews/drug/508095.html
3-bromo-pyrurvate directly inhibits hexokinase
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11578813&dopt=Abstract
========
Toxicity
========
It seems that there are no completed toxicity studies. The compound
appears to be non-toxic/low toxic, but no human studies have been
completed.
?In fact, Ko says she hasn't been able to find a toxic dose of the
compound, which blocks the two ways cancer cells make energy. In
earlier experiments with rabbits with liver cancer, reported in 2002,
no obvious toxic effects were seen, either. There is a patent pending
on possible cancer applications of the compound.?
http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=5600046
?Pedersen cautions that before 3-bromopyruvate could be tested in
humans, scientists would need to learn how normal cells protect
themselves, whether the compound causes long-term damage to normal
tissues, and how increasing the dose affects the animals. We assume
some level of the compound would be toxic," adds Pedersen. "Any drug
can be toxic, it's a matter of determining the limits."
http://harrisons.accessmedicine.com/amed/public/amed_news/news_article/1073.html
http://www.healthy.net/scr/news.asp?Id=10050
?My laboratory is also part of a translational research team focused
on identifying and developing new drugs for liver cancer, a disease
that is almost always fatal. One such agent is 3-bromopyruvic acid
(3-BrPA) that I discovered prior to my appointment to the faculty. We
are now studying this agent further to identify its cellular targets.
Previously, shown to inhibit liver implanted tumors and metastasis to
the lungs in an animal model, we have now shown that 3-BrPA exhibits
no apparent toxicity while significantly prolonging the lives of all
animals receiving therapy, and in some cases resulting in either
calcification or disappearance of the tumor. My laboratory is also
working on the mechanism of action of this unique anticancer agent,
and will soon be investigating its capacity to inhibit cancers derived
from other tissues.? - Dr. Young H. Ko, Johns Hopkins University 2003
(Page 65 of this document)
http://biolchem.bs.jhmi.edu/pdf/newsletter_2003.pdf
http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&id=8643&month=07&year=2002
Used to form other compounds
?Stable diastereomeric ethyl 1-benzoyl-6-(bromomethyl)-2,2,2,4-tetra-
phenyl-3,7-dioxa-2?5-phosphabicyclo[3.2.0]hept-4-ene-6-carboxylate was
obtained in 98% yield from the reaction between dibenzoylacetylene as
electron-deficient acetylenic compound, and ethyl 3-bromopyruvate in
the presence of triphenylphosphine in dry ether.?
http://taylorandfrancis.metapress.com/app/home/contribution.asp?wasp=99a0hcpddg1tpg9c67r2&referrer=parent&backto=issue,1,25;journal,4,29;linkingpublicationresults,1:102003,1
?The inactivation of tetrameric isocitrate lyase from Escherichia coli
by 3-bromopyruvate, exhibiting saturation kinetics, is accompanied by
the loss of one sulfhydryl per subunit.?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2183722&dopt=Abstract
?Tryptophanase purified from Escherichia coli B/It7-A was irreversibly
inactivated by 3-bromopyruvate following pseudo-first-order kinetics.?
http://jb.oupjournals.org/cgi/content/abstract/97/3/851
==========
Other Uses
==========
Studied as a potential TB drug.?The three-dimensional structure of M.
tuberculosis isocitrate lyase, in association with the simple
prototype inhibitors 3-bromopyruvate and 3-nitropyruvate,62 has been
solved, and the search is now underway for more drug-like molecules.?
Page 24
?A marked stimulation of insulin secretion and 45Ca2+ efflux rate was
observed in response to 3-fluoropyruvate and 3-bromopyruvate,
compounds which inhibited oxidative metabolism of [14C]glucose
and [14C]pyruvate in islets.?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=MEDLINE&list_uids=2405839
3-Bromopyruvic acid it seems has antimicrobial properties against
some species of yeast.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14253613&dopt=Abstract
An abstract ?Thiamin pyrophosphate- dependent inactivation by 3-bromopyruvate?
http://www.jbc.org/cgi/content/abstract/259/5/2905
?The deadend inhibitor was 3-bromopyruvate as a substrate analog of
pyruvate. Velocity was measured as a function of enzyme concentration
around the Km value of reactants and around the Ki value of inhibitor.
In all cases, the plots were linear.? Page 2
?3-bromopyruvate is a dead-end analog of pyruvate. Through varying the
concentration of pyruvate at several fixed concentration of
3-bromopyruvate, the dead-end inhibition patterns showed an
intersection on the ordinate, indicating that 3-bromopyruvate is
competitive vs. pyruvate? Page 3
http://journal.kcsnet.or.kr/publi/bul/bu02n5/765.pdf
Substrates for endogenous metabolism by mature boar spermatozoa A. R.
Jones and W. A. Bubb
Department of Biochemistry, The University of Sydney, Sydney NSW 2006, Australia
?3-Bromopyruvate hydrate (Aldrich Chemical Co.,
Milwaukee, WI) was recrystallized several times from dry chloroform
(melting point 54?578C). Aqueous solutions were neutralized with solid
NaHCO3 and added to incubations as sodium bromopyruvate (BPA) at a
final concentration of 0.5 mmol l?1. (R,S)-a-bromohydrin phosphate
biscyclohexylamine
salt was prepared to established purity by the method of Jones and
Gillan (1996a). All enzymes and substrates were supplied by Boehringer
Mannheim (Castle Hill, NSW) and compounds were prepared as aqueous
solutions and used at concentrations indicated in the text. All other
chemicals and
reagents were of analytical grade and all solutions were prepared in
water purified by reverse osmosis.? Page 1
Page 3
?Addition at any time of 3-
bromopyruvate (BPA), which inhibits stage 2 of the glycolytic pathway
(Jones et al., 1995), caused an immediate decrease in the ECP. In
incubations containing BPA at time 0, the ECP rapidly decreased over
the first few hours, but showed a gradual increase from about 5 h
(Fig. 1b). When incubated in the presence of (R,S)-a-bromohydrin
phosphate, an inhibitor of the FAD-linked mitochondrial glycerol
3-phosphate
dehydrogenase (Jones and Gillan, 1996a), the ECP decreased steadily
over the first 5 h but showed some slight increase at 9 h ?
http://www.reproduction-online.org/cgi/reprint/119/1/129.pdf
The Anti-Glycolytic Activity of 3-Bromopyruvate on Mature Boar
Spermatozoa in Vitro 317 -- 320 A.R. Jones, L. Gillan, D. Milmlow
?Both lactate and glycerol 3-phosphate underwent oxidation and these
substrates continued to be metabolized by this preparation which had
been stored for up to 10 days at 4°C. Such preparations may be of
assistance in the investigation of the biochemistry of boar sperm
mitochondria.?
http://publish.csiro.au/paper/R97048.htm
?Bromopyruvate has been used for alkylation of protein SH groups and
through its 2-oxo group it can form a hydrazone with
N4-aminocytosine.?
http://www.ejbiochem.org/cgi/content/abstract/157/2/427
Hope this helps you out. If any part of my answer is unclear, please
request an Answer Clarification, before rating. This will allow me to
assist you further, if possible.
Regards,
crabcakes
Search Terms
3-BrPA
3-bromopyruvate
3-bromopyruvic acid
3-bromo-pyruvate
3-bromo-pyruvic acid
chemical naming conventions
pyruvate
pyruvic acid |
