Bromopyruvic acid

Structural formula
General
Surname	Bromopyruvic acid
other names	3-bromo-2-oxopropionic acid 3-bromopyruvate 3-bromopyruvate 3-BP 3BP
Molecular formula	C 3 H 3 BrO 3
Brief description	white solid
External identifiers / databases
CAS number 1113-59-3 EC number 214-206-5 ECHA InfoCard 100.012.915 PubChem 70684 ChemSpider 63850 Wikidata Q3608257
properties
Molar mass	166.96 g mol −1
Physical state	firmly
density	1.73 g cm −3
Melting point	77-82 ° C
solubility	soluble in water (1 g / 10 ml) soluble in dimethyl sulfoxide and ethyl acetate
Refractive index	1.465
safety instructions
GHS labeling of hazardous substances danger H and P phrases H: 314 P: 280-305 + 351 + 338-310
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Bromopyruvic acid (also: 3-bromopyruvate or 3-bromopyruvate ; short: 3-BP ) is an organic chemical compound from the group of derivatives of pyruvic acid . 3-bromine o pyruvate is an English-language substance name that is often adopted in the general German language, but is technically incorrect.

The salts and esters of bromopyruvic acid are known as 3-bromopyruvates .

Extraction and presentation

Bromopyruvic acid can be obtained by bromination of pyruvic acid using bromine in the presence of sulfuric acid.

properties

Bromopyruvic acid is a white solid that is soluble in water.

Potential uses

Bromopyruvic acid is believed to be an affinity marker for cysteine ​​residues . It is also involved in the synthesis of imidazo [1,2- a ] pyridine-2-carboxylic acids and substituted pyrones .

Chemically speaking, bromopyruvic acid is an alkylane . The postulated oncological mechanism of action is via glycolysis (inhibition of the enzyme glyceraldehyde-3-phosphate dehydrogenase and the enzyme hexokinase II) and the mitochondria . The compound is being discussed as a potential cytostatic agent against, for example, lung cancer . In an animal study in 2004, a complete regression of xenografts from hepatocellular carcinoma cells was observed in 19 rats , which made their use for further clinical studies appear interesting. The compound is not approved as a cancer drug in Germany and has not yet been adequately researched. ClinicalTrials.gov does not have any clinical trials on patients with bromopyruvic acid registered.

In animal experiments, the considerable side effects, such as liver necrosis , could be significantly reduced by an intra-arterial infusion. The US company PreScience Labs has had orphan drug status for intraarterially administered bromopyruvic acid (company name: PSL-001) for the treatment of rare forms of pancreatic carcinoma ( rare carcinoma of pancreas ) since 2014 . The company states on its website that the FDA approved patient enrollment for a Phase I trial in January 2013, which the company was planning to begin in 2015. The company also states on its website that PSL-001 was used on patients from 2010 to 2012 as part of compassionate use . PreScience Labs is the exclusive licensee of bromopyruvic acid patents from Johns Hopkins University . Contrary to the company's announcement, the Phase I study has not yet started (as of August 2016).

Trivia

At the end of July 2016 it became public that at least three people had died after alternative medical treatment by an alternative practitioner in a natural medicine practice in Brüggen , which also involved bromopyruvic acid. As a result, there was a police investigation, which as of August 18 was expanded to 70 deaths related to the practice. In another report in 2016, the public prosecutor was quoted as saying that the therapy in question did not have to be the cause of death, as patients who had terminal cancer often visited the practice. In April 2018, the health practitioner was charged with negligent homicide in three cases by the Krefeld public prosecutor's office, because the drug he overdosed was forensically verifiable as the cause of the death of the three patients who had died. In July 2019, the alternative practitioner was sentenced to two years' probation for negligent homicide, stating a "serious breach of duty of care".

Individual evidence

1. ↑ ^{a b c d e f g} Data sheet Bromopyruvic acid, ≥97.0% (T) from Sigma-Aldrich , accessed on August 6, 2016 ( PDF ).
2. ^ ^{A b} Carl L. Yaws: The Yaws Handbook of Physical Properties for Hydrocarbons and Chemicals: Physical Properties for More Than 54,000 Organic and Inorganic Chemical Compounds, Coverage for C1 to C100 Organics and Ac to Zr Inorganics . Gulf Professional Publishing, 2015, ISBN 978-0-12-801146-1 ( Google Books ).
3. ↑ ^{a b c} Datasheet Bromopyruvic acid, 97% from AlfaAesar, accessed on August 7, 2016 ( PDF )(JavaScript required) .
4. ↑ Manojkumar R. Bhandari, Carl J. Lovely: Encyclopedia of Reagents for Organic Synthesis . 2001, ISBN 978-0-470-84289-8 , 3-Bromopyruvic Acid, doi : 10.1002 / 047084289X.rn01049 .
5. ↑ Ebi Web Team: 3-bromopyruvic acid (CHEBI: 131461). In: ebi.ac.uk. March 21, 2016, accessed on August 22, 2016 . 
6. ^ P. Dell'Antone: Targets of 3-bromopyruvate, a new, energy depleting, anticancer agent. In: Medicinal chemistry. Volume 5, Number 6, November 2009, pp. 491-496, PMID 19534685 .
7. ↑ ^{a b} rme: Warburg effect: How 3-bromopyruvate is supposed to defeat cancer. In: aerzteblatt.de . August 15, 2016. Retrieved August 24, 2016 . 
8. ↑ MC Shoshan: 3-Bromopyruvate: targets and outcomes. In: Journal of bioenergetics and biomembranes. Volume 44, Number 1, February 2012, pp. 7-15, doi : 10.1007 / s10863-012-9419-2 , PMID 22298255 (review).
9. ↑ Peter L. Pedersen: 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 . In: Journal of Bioenergetics and Biomembranes . tape 44 , no. 1 , March 2012, p. 1-6 , doi : 10.1007 / s10863-012-9425-4 .
10. ↑ Sandra S. Meyer: Glucose metabolism and radiation therapy of solid, malignant tumors , dissertation 2011, urn : nbn: de: hebis: 77-30740 .
11. ↑ ^{a b} Deaths after Alternative Cancer Therapy: Questionable Methods. In: Spiegel Online . Retrieved August 7, 2016 . 
12. ↑ M. Vali, E. Liapi et al. a .: Intraarterial therapy with a new potent inhibitor of tumor metabolism (3-bromopyruvate): identification of therapeutic dose and method of injection in an animal model of liver cancer. In: Journal of vascular and interventional radiology: JVIR. Volume 18, number 1 Pt 1, January 2007, pp. 95-101, doi : 10.1016 / j.jvir.2006.10.019 , PMID 17296709 .
13. ↑ Orphanet: 3 bromopyruvates. In: orpha.net. August 23, 2016, accessed on August 24, 2016 . 
14. ^ PreScience Labs: a Bio-Pharmecutical company developing anti-cancer drugs. (No longer available online.) In: presciencelabs.com. April 6, 2013, archived from the original on August 3, 2016 ; accessed on August 24, 2016 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  
15. ^ PreScience Labs: Clinical Development. (No longer available online.) In: presciencelabs.com. April 6, 2013, archived from the original on August 11, 2016 ; accessed on August 24, 2016 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  
16. ↑ US 7,547,673
17. ↑ US 2010/0203110
18. ^ Anti-cancer drug technology, PSL-001. (No longer available online.) In: presciencelabs.com. April 6, 2013, archived from the original on August 8, 2016 ; accessed on August 24, 2016 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  
19. ^ Cancer Center Brüggen: investigations into 70 deaths. (No longer available online.) In: wdr1.de. Archived from the original on August 24, 2016 ; accessed on August 18, 2016 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  
20. ↑ Deaths after cancer therapy: alternative practitioners were allowed to use experimental active ingredients. In: Spiegel Online . Retrieved August 27, 2016 . 
21. ↑ Martin Röse: Negligent killing of cancer patients: public prosecutor accuses Brüggen naturopaths. Retrieved April 17, 2018 . 
22. ^ Death of three cancer patients: Krefeld public prosecutor accuses naturopaths . In: Spiegel Online . April 12, 2018 ( spiegel.de [accessed April 17, 2018]).
23. ↑ Death of cancer patients - suspended sentence for alternative practitioners . In: Spiegel Online . July 15, 2019 ( spiegel.de [accessed July 15, 2019]).