Bromopyruvic acid

Bromopyruvic acid

Names
IUPAC name 3-Bromo-2-oxopropanoic acid
Other names Bromopyruvate 3-Bromopyruvic acid 3-Bromopyruvate 3-BrPA 3BP 3-Br-Pyr
Identifiers
CAS Number	1113-59-3
ChEBI	CHEBI:131461
ChEMBL	ChEMBL177837
ChemSpider	63850
Jmol 3D model	Interactive image Interactive image
PubChem	70684
InChI InChI=1S/C3H3BrO3/c4-1-2(5)3(6)7/h1H2,(H,6,7) Key: PRRZDZJYSJLDBS-UHFFFAOYSA-N InChI=1/C3H3BrO3/c4-1-2(5)3(6)7/h1H2,(H,6,7) Key: PRRZDZJYSJLDBS-UHFFFAOYAU
SMILES C(C(=O)C(=O)O)Br BrCC(=O)C(=O)O
Properties
Chemical formula	C3H3BrO3
Molar mass	166.96 g·mol^−1
Melting point	79 to 82 °C (174 to 180 °F; 352 to 355 K) (hydrate)
Hazards
R-phrases	R34
S-phrases	S25 S36/37/39 S45
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Bromopyruvic acid and its alkaline form, bromopyruvate, are synthetic brominated derivatives of pyruvic acid. They are lactic acid and pyruvate analogs.

The characteristics of bromopyruvate in vitro and in vivo have been reported in the scientific literature since the 1940s. Because it is a highly reactive alkylating agent and it is inherently unstable, it had been described as a metabolic poison.

Research activity

In 1993, researchers at the Johns Hopkins School of Medicine reported that a pyruvate transporter system could be used to deliver bromopyruvate inside trypanosomal cells where its primary target is glyceraldehyde-3-phosphate dehydrogenase, which is highly sensitive to inhibition by bromopyruvate.^[1] The pyruvate transporter system, which is known to be overexpressed in cancer cells, was later identified to be a MCT called Monocarboxylate Transporter 1.^[2] A 2002 study suggested that intra-arterial delivery of bromopyruvic acid directly to the site of tumors in rabbits could represent a strategy for stopping the growth of liver cancer while minimizing toxic side-effects.^[3] An application for patent has been submitted.^[4]

Research at Johns Hopkins has suggested that bromopyruvate could be used to selectively kill cancer cells, while leaving normal cells intact.^[5][6] A Johns Hopkins press release dated October 14, 2004 stated that, "Building on their earlier work, Johns Hopkins researchers have discovered that an apparently nontoxic cellular "energy blocker" can eradicate large liver tumors grown in rats. In July 2013, the FDA accepted an IND application for the use of bromopyruvate for a Phase I clinical trial in liver cancer.^[7]

References

1. Barnard, JP; Reynafarje, B; Pedersen, PL (1993). "Glucose catabolism in African trypanosomes. Evidence that the terminal step is catalyzed by a pyruvate transporter capable of facilitating uptake of toxic analogs". The Journal of Biological Chemistry 268 (5): 3654–3661. PMID 8429041.
2. Liu, Zhe; Sun, Yiming; Hong, Haiyu; Zhao, Surong; Zou, Xue; Ma, Renqiang; Jiang, Chenchen; Wang, Zhiwei; Li, Huabin (2015-08-15). "3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells". American Journal of Cancer Research 5 (9): 2673–2685. ISSN 2156-6976. PMC 4633897. PMID 26609475.
3. Geschwind, JF; Ko, YH; Torbenson, MS; Magee, C; Pedersen, PL (2002). "Novel therapy for liver cancer: Direct intraarterial injection of a potent inhibitor of ATP production". Cancer Research 62 (14): 3909–13. PMID 12124317.
4. Therapeutics for cancer using 3-bromopyruvate and other selective inhibitors of ATP production
5. Pedersen, Peter L. (2012). "3-bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: Introduction to a special issue". Journal of Bioenergetics and Biomembranes 44 (1): 1–6. doi:10.1007/s10863-012-9425-4. PMID 22382780.
6. Ko, Y. H.; Verhoeven, H. A.; Lee, M. J.; Corbin, D. J.; Vogl, T. J.; Pedersen, P. L. (2012). "A translational study "case report" on the small molecule "energy blocker" 3-bromopyruvate (3BP) as a potent anticancer agent: From bench side to bedside". Journal of Bioenergetics and Biomembranes 44 (1): 163–70. doi:10.1007/s10863-012-9417-4. PMID 22328020.
7. "PreScience Labs Announced that the FDA Accepts IND Application for Novel Oncology Drug" (Press release). Reuters. 24 July 2013.

External links

• Mathupala, Saroj P.; Ko, Young H.; Pedersen, Peter L. (2010). "The pivotal roles of mitochondria in cancer: Warburg and beyond and encouraging prospects for effective therapies". Biochimica et Biophysica Acta (BBA) - Bioenergetics 1797 (6–7): 1225–1230. doi:10.1016/j.bbabio.2010.03.025.
• Mathupala, Saroj P.; Ko, Young H.; Pedersen, Peter L. (2009). "Hexokinase-2 bound to mitochondria: Cancer's stygian link to the "Warburg effect" and a pivotal target for effective therapy". Seminars in Cancer Biology 19 (1): 17–24. doi:10.1016/j.semcancer.2008.11.006. PMC 2714668. PMID 19101634.
• Ko, Young H.; Smith, Barbara L.; Wang, Yuchuan; Pomper, Martin G.; Rini, David A.; Torbenson, Michael S.; Hullihen, Joanne; Pedersen, Peter L. (2004). "Advanced cancers: Eradication in all cases using 3-bromopyruvate therapy to deplete ATP". Biochemical and Biophysical Research Communications 324 (1): 269–75. doi:10.1016/j.bbrc.2004.09.047. PMID 15465013.
• Mathupala, S P; Ko, Y H; Pedersen, P L (2006). "Hexokinase II: Cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria". Oncogene 25 (34): 4777–86. doi:10.1038/sj.onc.1209603. PMC 3385868. PMID 16892090.
• The cancer cell's "power plants" as promising therapeutic targets: An overview, by Peter Pederson