Bromopyruvic acid

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ImageFile=Bromopyruvic acid.pngImageSize=180px
IUPACName=3-Bromo-2-oxopropanoic acid
OtherNames=Bromopyruvate
3-Bromopyruvic acid
3-Bromopyruvate
3-BrPA
Section1= Chembox Identifiers
CASNo=1113-59-3
PubChem=70684
SMILES=C(C(=O)C(=O)O)Br
Section2= Chembox Properties
Formula=C₃H₃BrO₃
MolarMass=166.95812
Appearance=
Density=
MeltingPt=79-82 °C (hydrate)
BoilingPt=
Solubility=
Section3= Chembox Hazards
MainHazards=
FlashPt=
Autoignition=
RPhrases = R34
SPhrases = S25 S36/37/39 S45

Bromopyruvic acid, or bromopyruvate, is a synthetic brominated derivative of pyruvic acid. It is being studied as a potential treatment for certain types of cancer. Initial studies in laboratory animals by Dr. Young H. Ko showed that bromopyruvic acid is effective at eliminating aggressive liver tumors.cite journal |author=Ko YH, Pedersen PL, Geschwind JF |title=Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase |journal=Cancer Lett. |volume=173 |issue=1 |pages=83–91 |year=2001 |pmid=11578813 |doi=]

According to the Warburg hypothesis, unlike normal tissues that derive most of their energy in the form of adenosine triphosphate (ATP) by metabolizing glucose in the mitochondria, aggressive cancers obtain much of their ATP by metabolizing glucose directly to lactic acid. [cite journal |author=Pedersen PL |title=Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen |journal= |volume= |issue= |pages= |year=2007 |pmid=17879147 |doi=10.1007/s10863-007-9094-x] The mechanism of action of bromopyruvic acid involves interruption of this latter process by the inhibition of the enzyme hexokinase II because the bromopyruvic acid is similar in chemical structure to lactic acid.

Further study demonstrated that when 19 rats with advanced cancers (generated by seeding with hepatocellular carcinoma cells) were treated with bromopyruvic acid, the cancers were eradicated without apparent toxicity or recurrence in all treated animals. [cite journal |author=Ko YH, Smith BL, Wang Y, "et al" |title=Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP |journal=Biochem. Biophys. Res. Commun. |volume=324 |issue=1 |pages=269–75 |year=2004 |pmid=15465013 |doi=10.1016/j.bbrc.2004.09.047] Another study reported that intraarterial delivery of bromopyruvic acid directly to the site of a tumor, followed by systemic delivery only when necessary, represents a new strategy for stopping the growth of liver and other cancers, while minimizing toxic side effects. [cite journal |author=Geschwind JF, Ko YH, Torbenson MS, Magee C, Pedersen PL |title=Novel therapy for liver cancer: direct intraarterial injection of a potent inhibitor of ATP production |journal=Cancer Res. |volume=62 |issue=14 |pages=3909–13 |year=2002 |pmid=12124317 |doi=]

While pre-clinical studies have been promising, human clinical trials to study the effectiveness of bromopyruvic acid have not yet begun. One obstacle to further development of bromopyruvic acid as a pharmaceutical treatment for cancer is that since bromopyruvic acid is not a novel chemical compound, it is not patentable. [ [http://www.liver-cancer-net.org/news/liver-cancer-news-0001.htm Young researcher stalks cancer] ] Without the exclusivity allowed by patent protection, there is little prospect for recovery of the high financial investment needed for conducting the clinical trials required by worldwide regulatory agencies for approval of pharmaceutical drugs.

References

External links

* [http://lib.bioinfo.pl/pmid:17404823 The cancer cell's "power plants" as promising therapeutic targets: An overview] , by Peter Pederson
* [http://acs.confex.com/acs/norm07/techprogram/P44814.HTM Glycolytic enzyme inhibitors as novel anti-cancer drugs] , James C.K. Lai "et al"., Idaho State, June 2007
* [http://www.emphycorp.com/cancerprevention.html Pyruvate in Cancer Prevention and Treatment]
* [http://www.hopkinskimmelcancercenter.org/news/details.cfm?documentid=673 Energy Blocker Kills Big Tumors in Rats]
* [http://www.ltd.jhu.edu/explore_inventions/index.html?MSID=105&JCatName=BS3&Show=Detail 3-Bromopyruvic Acid As a Potent Anticancer Agent Delivered Intraarterially]