Roxadustat

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Structural formula
Structural formula of Fg-4592
General
Surname Roxadustat
other names

FG-4592

Molecular formula C 19 H 16 N 2 O 5
External identifiers / databases
CAS number 808118-40-3
ECHA InfoCard 100.245.356
PubChem 11256664
ChemSpider 9431690
Wikidata Q27088611
Drug information
ATC code

B03 XA05

properties
Molar mass 352.34 g mol −1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Roxadustat (FG-4592, AZD9941 or ASP1517, Evrenzo® in Japan) is as EPO , a prolyl hydroxylase inhibitor (HIF-PHI), so an inhibitor ( inhibitor ) of the prolyl hydroxylase enzymes that the hypoxia-inducible factors would degrade when another normal oxygen supply (normoxia) is achieved. As a first-in-class HIF stabilizer (HIF-PHI), it is the first representative of a new drug class for the potential treatment of anemia in chronic kidney disease (CKD). Roxadustat is jointly developed and marketed by AstraZeneca and FibroGen . The substance is currently still in the approval process or in clinical testing in development phase III .

Roxadustat is an orally administered, small molecule drug that has already been approved in China and since 09/2019 also in Japan (under the trade name Evrenzo) for the treatment of patients with anemia caused by CKD on dialysis . Roxadustat promotes erythropoiesis by increasing endogenous production of erythropoietin , improving iron regulation, and overcoming the negative effects of inflammation on hemoglobin synthesis and red blood cell production by downregulating hepcidin . Administration of roxadustat induces coordinated erythropoiesis, which increases red blood cell counts while maintaining plasma erythropoietin levels at or near normal physiological levels.

Possible side effects:

  • Hyperkalemia (increased potassium levels)
  • Metabolic acidosis (acidification of the blood and body)
  • Inhibition of cholesterol synthesis via u. a. HMG-CoA reductase (comparable to statins)
  • Increase in VEGF, a signal protein that promotes tumor growth
  • Pulmonary hypertension (high pulmonary pressure)

Roxadustat is used such as B. Molidustat - illegally - abused for doping .

Other substances in the drug class:

literature

  • M. Thevis, W. Schänzer: Analytical approaches for the detection of emerging therapeutics and non-approved drugs in human doping controls. In: J Pharm Biomed Anal. Volume 101, 2014, pp. 66-83
  • S. Beuck, W. Bornatsch, A. Lagojda, W. Schänzer, M Thevis: Development of liquid chromatography-tandem mass spectrometry-based analytical assays for the determination of HIF stabilizers in preventive doping research. In: Drug Testing and Analysis Volume 3, 2011, No. 11-12, pp. 756-770.
  • M. Thevis, W. Schänzer: Doping substances of the future and their detection. Selective androgen receptor modulators (SARMs) and HIF stabilizers. In: FIT the science magazine. Volume 1, 2009, pp. 14-17

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ a b Phase III OLYMPUS and ROCKIES trials for roxadustat met their primary endpoints in chronic kidney disease patients with anemia , PM AstraZeneca, December 20, 2018, accessed on January 17, 2019
  3. ↑ Evrenzo® (roxadustat) Tablets Approved in Japan for the Treatment of Anemia Associated with Chronic Kidney Disease in Dialysis Patients | Astellas Pharma Inc. GLOBAL WEBSITE. Accessed December 2, 2019 .
  4. ↑ Chen N, Hao C, Peng X, Lin H, Yin A, Hao L, Tao Y, Liang X, Liu Z, Xing C, Chen J, Luo L, Zuo L, Liao Y, Liu BC, Leong R, Wang C, Liu C, Neff T, Szczech L, Yu KP: Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis . In: The New England Journal of Medicine . 381, No. 11, September 2019, pp. 1001-1010. doi : 10.1056 / NEJMoa1813599 . PMID 31340089 .
  5. ↑ Zhou M, Hou J, Li Y, Mou S, Wang Z, Horch RE, Sun J, Yuan Q: The pro-angiogenic role of hypoxia inducible factor stabilizer FG-4592 and its application in an in vivo tissue engineering chamber model . In: Scientific Reports . 9, No. 1, April 2019, p. 6035. bibcode : 2019NatSR ... 9.6035Z . doi : 10.1038 / s41598-019-41924-5 . PMID 30988335 . PMC 6465281 (free full text).
  6. ↑ Cygulska K, Wejner-Mik P, Plewka M, Figiel Ł, Chrzanowski Ł, Kasprzak JD: Roxadustat: another drug that causes pulmonary hypertension? Report of first human case . In: Polish Archives of Internal Medicine . 129, No. 5, May 2019, pp. 344-345. doi : 10.20452 / pamw.4445 . PMID 30758318 .
  7. ↑ HIF stabilizers , German Sport University Cologne, accessed on January 17, 2019