Roxadustat

Roxadustat
Clinical data
Other names	FG-4592
ATC code	B03XA05 (WHO) ;
Identifiers
	IUPAC name 2-[(4-Hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid;
CAS Number	808118-40-3;
PubChem CID	11256664;
DrugBank	DB04847;
ChemSpider	9431690;
UNII	X3O30D9YMX;
KEGG	D10593;
CompTox Dashboard (EPA)	DTXSID60230644 ;
ECHA InfoCard	100.245.356
Chemical and physical data
Formula	C19H16N2O5
Molar mass	352.346 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=NC(=C(C2=C1C=C(C=C2)OC3=CC=CC=C3)O)C(=O)NCC(=O)O;
	InChI InChI=1S/C19H16N2O5/c1-11-15-9-13(26-12-5-3-2-4-6-12)7-8-14(15)18(24)17(21-11)19(25)20-10-16(22)23/h2-9,24H,10H2,1H3,(H,20,25)(H,22,23); Key:YOZBGTLTNGAVFU-UHFFFAOYSA-N;

Roxadustat (INN, also known as FG-4592, ASP1517 and AZD9941) is a drug which acts as a HIF prolyl-hydroxylase inhibitor and thereby increases endogenous production of erythropoietin, which stimulates production of hemoglobin and red blood cells. It is in Phase III clinical trials for the treatment of anemia secondary to chronic kidney disease.[1][2] Due to its potential applications in athletic doping, it has also been incorporated into screens for performance-enhancing drugs, as it has already been detected being used illicitly by athletes despite not having yet been approved for medical use.[3][4][5] Roxadustat received its first global approval in China on 17 December 2018 for the treatment of anaemia caused by CKD in patients who are dialysis-dependent.[6] Roxadustat is reported to increase VEGF, a signal protein that can activate tumor growth[7] and also is considered to cause pulmonary hypertension.[8]

References

Provenzano, R.; Besarab, A.; Sun, C. H.; Diamond, S. A.; Durham, J. H.; Cangiano, J. L.; Aiello, J. R.; Novak, J. E.; Lee, T.; Leong, R.; Roberts, B. K.; Saikali, K. G.; Hemmerich, S.; Szczech, L. A.; Yu, K. H.; Neff, T. B. (2016). "Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD". Clinical Journal of the American Society of Nephrology. 11 (6): 982–91. doi:10.2215/CJN.06890615. PMC 4891748. PMID 27094610.
Becker, K.; Saad, M. (2017). "A New Approach to the Management of Anemia in CKD Patients: A Review on Roxadustat". Advances in Therapy. 34 (4): 848–853. doi:10.1007/s12325-017-0508-9. PMID 28290095.
Beuck, S.; Schänzer, W.; Thevis, M. (2012). "Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis". Drug Testing and Analysis. 4 (11): 830–45. doi:10.1002/dta.390. PMID 22362605.
Buisson, C.; Marchand, A.; Bailloux, I.; Lahaussois, A.; Martin, L.; Molina, A. (2016). "Detection by LC-MS/MS of HIF stabilizer FG-4592 used as a new doping agent: Investigation on a positive case". Journal of Pharmaceutical and Biomedical Analysis. 121: 181–187. doi:10.1016/j.jpba.2016.01.029. PMID 26808067.
Eichner, D.; Van Wagoner, R. M.; Brenner, M.; Chou, J.; Leigh, S.; Wright, L. R.; Flippin, L. A.; Martinelli, M.; Krug, O.; Schänzer, W.; Thevis, M. (2017). "Lmplementation of the prolyl hydroxylase inhibitor Roxadustat (FG-4592) and its main metabolites into routine doping controls". Drug Testing and Analysis. 9 (11–12): 1768–1778. doi:10.1002/dta.2202. PMID 28378453.
Dhillon S. Roxadustat: First Global Approval.Drugs (2019) 79:563–572 https://doi.org/10.1007/s40265-019-01077-1
Zhou, M.; Hou, J.; Li, Y.; Mou, S.; Wang, Z.; Horch, R. E.; Sun, J.; Yuan, Q. (2019). "The pro-angiogenic role of hypoxia inducible factor stabilizer FG-4592 and its application in an in vivo tissue engineering chamber model". Sci. Rep. 9 (1): 6035. doi:10.1038/s41598-019-41924-5. PMC 6465281. PMID 30988335.
Cygulska, K.; Wejner-Mik, P.; Plewka, M.; Figiel, Ł.; Chrzanowski, Ł.; Kasprzak, J. D. (2019). "Roxadustat - another drug that causes pulmonary hypertension? - Report of first human case". Pol. Arch. Intern. Med. 129 (5): 344–345. doi:10.20452/pamw.4445. PMID 30758318.

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[1] Provenzano, R.; Besarab, A.; Sun, C. H.; Diamond, S. A.; Durham, J. H.; Cangiano, J. L.; Aiello, J. R.; Novak, J. E.; Lee, T.; Leong, R.; Roberts, B. K.; Saikali, K. G.; Hemmerich, S.; Szczech, L. A.; Yu, K. H.; Neff, T. B. (2016). "Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD". Clinical Journal of the American Society of Nephrology. 11 (6): 982–91. doi:10.2215/CJN.06890615. PMC 4891748. PMID 27094610.

[2] Becker, K.; Saad, M. (2017). "A New Approach to the Management of Anemia in CKD Patients: A Review on Roxadustat". Advances in Therapy. 34 (4): 848–853. doi:10.1007/s12325-017-0508-9. PMID 28290095.

[3] Beuck, S.; Schänzer, W.; Thevis, M. (2012). "Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis". Drug Testing and Analysis. 4 (11): 830–45. doi:10.1002/dta.390. PMID 22362605.

[4] Buisson, C.; Marchand, A.; Bailloux, I.; Lahaussois, A.; Martin, L.; Molina, A. (2016). "Detection by LC-MS/MS of HIF stabilizer FG-4592 used as a new doping agent: Investigation on a positive case". Journal of Pharmaceutical and Biomedical Analysis. 121: 181–187. doi:10.1016/j.jpba.2016.01.029. PMID 26808067.

[5] Eichner, D.; Van Wagoner, R. M.; Brenner, M.; Chou, J.; Leigh, S.; Wright, L. R.; Flippin, L. A.; Martinelli, M.; Krug, O.; Schänzer, W.; Thevis, M. (2017). "Lmplementation of the prolyl hydroxylase inhibitor Roxadustat (FG-4592) and its main metabolites into routine doping controls". Drug Testing and Analysis. 9 (11–12): 1768–1778. doi:10.1002/dta.2202. PMID 28378453.

[6] Dhillon S. Roxadustat: First Global Approval.Drugs (2019) 79:563–572 https://doi.org/10.1007/s40265-019-01077-1

[7] Zhou, M.; Hou, J.; Li, Y.; Mou, S.; Wang, Z.; Horch, R. E.; Sun, J.; Yuan, Q. (2019). "The pro-angiogenic role of hypoxia inducible factor stabilizer FG-4592 and its application in an in vivo tissue engineering chamber model". Sci. Rep. 9 (1): 6035. doi:10.1038/s41598-019-41924-5. PMC 6465281. PMID 30988335.

[8] Cygulska, K.; Wejner-Mik, P.; Plewka, M.; Figiel, Ł.; Chrzanowski, Ł.; Kasprzak, J. D. (2019). "Roxadustat - another drug that causes pulmonary hypertension? - Report of first human case". Pol. Arch. Intern. Med. 129 (5): 344–345. doi:10.20452/pamw.4445. PMID 30758318.

Roxadustat

See also

References