Roxadustat | CAS#317133 | HIF α prolyl hydroxylase inhibitor

MedKoo Cat#: 317133 | Name: Roxadustat

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Roxadustat, also known as ASP1517 and FG-4592, is an HIF α prolyl hydroxylase inhibitor in a cell-free assay. It stabilizes HIF-2 and induces EPO production and stimulates erythropoiesis. Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin.

Chemical Structure

Roxadustat

CAS#808118-40-3 (free)

Theoretical Analysis

MedKoo Cat#: 317133

Name: Roxadustat

CAS#: 808118-40-3 (free)

Chemical Formula: C19H16N2O5

Exact Mass: 352.1059

Molecular Weight: 352.35

Elemental Analysis: C, 64.77; H, 4.58; N, 7.95; O, 22.70

Price and Availability

Size	Price	Availability
25mg	USD 110.00	Ready to ship
50mg	USD 180.00	Ready to ship
100mg	USD 300.00	Ready to ship
200mg	USD 500.00	Ready to ship
500mg	USD 1,050.00	Ready to ship
1g	USD 1,950.00	Ready to ship
2g	USD 3,450.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

2043026-13-5 (d5-labeled) 808118-40-3 (free) 1537180-01-0 (HCl) 1537180-03-2 (mesylate) 1537179-94-4 (sodium) 1537179-95-5 (potassium)

Synonym

ASP1517; ASP 1517; ASP-1517; FG-4592; FG 4592; FG4592; Roxadustat.

IUPAC/Chemical Name

(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)glycine

InChi Key

YOZBGTLTNGAVFU-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

O=C(O)CNC(C1=C(O)C2=C(C(C)=N1)C=C(OC3=CC=CC=C3)C=C2)=O

Appearance

White to off- white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC70417

QC Data

View QC data: current batch, Lot#TZC70417

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Roxadustat is an inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH; IC50s = 1.4, 1.26, and 1.32 µM for HIF-PH1, HIF-PH2, and HIF-PH3, respectively). It is selective for HIF-PH over other 2-oxoglutarate-dependent dioxygenases, including lysine-specific demethylase 5A (KDM5A), KDM5B, -5C, -5D, and -6B (IC50s = >100 µM for all). Roxadustat (10-200 µM) stabilizes HIF-1α and HIF-2α in Hep3B hepatocellular carcinoma cells.

In vitro activity:

The in vitro effects of roxadustat on cobalt chloride (CoCl2)-stimulated pulmonary fibrosis were investigated with L929 mouse fibroblasts. The proliferation of L929 cells was inhibited and the production of collagen I, collagen III, prolyl hydroxylase domain protein 2 (PHD2), HIF-1α, α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1) and p-Smad3 were reduced relative to that in the CoCl2 after roxadustat treatment. Reference: Toxicol Lett. 2020 Oct 1;331:112-121. https://www.sciencedirect.com/science/article/abs/pii/S0378427420302745?via%3Dihub

In vivo activity:

The effects of roxadustat on an in vivo pulmonary fibrosismice model induced with bleomycin (BLM; intraperitoneal injection, 50 mg/kg twice a week for 4 continuous weeks) were investigated. Roxadustat ameliorated pulmonary fibrosis by reducing the pathology score and collagen deposition as well as decreasing the expression of collagen I, collagen III, PHD2, HIF-1α, α-SMA, CTGF, TGF-β1 and p-Smad3/Smad3. Reference: Toxicol Lett. 2020 Oct 1;331:112-121. https://www.sciencedirect.com/science/article/abs/pii/S0378427420302745?via%3Dihub

	Solvent	mg/mL	mM
Solubility
	DMSO	66.7	189.22
	DMF	50.0	141.90
	Ethanol	0.1	0.28

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 352.35 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Huang H, Wang X, Zhang X, Wang H, Jiang W. Roxadustat attenuates experimental pulmonary fibrosis in vitro and in vivo. Toxicol Lett. 2020 Oct 1;331:112-121. doi: 10.1016/j.toxlet.2020.06.009. Epub 2020 Jun 10. PMID: 32534005. 2. Qu N, Chen L, Liang S, Wei M, Sun L, He Q, Xue J, Wang M, Shi K, Jiang H, Liu H. Roxadustat Attenuates the Disruption of Epithelial Tight Junction in Caco2 Cells and a Rat Model of CKD Through MicroRNA-223. Front Med (Lausanne). 2022 Apr 13;9:850966. doi: 10.3389/fmed.2022.850966. PMID: 35492370; PMCID: PMC9043115. 3. Tao X, Pan X, Rui Y, Xue M. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats. Open Med (Wars). 2023 Jul 31;18(1):20230762. doi: 10.1515/med-2023-0762. PMID: 37554150; PMCID: PMC10404892. 4. Chen J, Lin X, Yao C, Bingwa LA, Wang H, Lin Z, Jin K, Zhuge Q, Yang S. Transplantation of Roxadustat-preconditioned bone marrow stromal cells improves neurological function recovery through enhancing grafted cell survival in ischemic stroke rats. CNS Neurosci Ther. 2022 Oct;28(10):1519-1531. doi: 10.1111/cns.13890. Epub 2022 Jun 13. PMID: 35695696; PMCID: PMC9437235.

In vitro protocol:

In vivo protocol:

1. Tao X, Pan X, Rui Y, Xue M. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats. Open Med (Wars). 2023 Jul 31;18(1):20230762. doi: 10.1515/med-2023-0762. PMID: 37554150; PMCID: PMC10404892. 2. Chen J, Lin X, Yao C, Bingwa LA, Wang H, Lin Z, Jin K, Zhuge Q, Yang S. Transplantation of Roxadustat-preconditioned bone marrow stromal cells improves neurological function recovery through enhancing grafted cell survival in ischemic stroke rats. CNS Neurosci Ther. 2022 Oct;28(10):1519-1531. doi: 10.1111/cns.13890. Epub 2022 Jun 13. PMID: 35695696; PMCID: PMC9437235.

1: Biedunkiewicz B, Jankowska M, Komorniczak M, Tylicki L, Dębska-Ślizień A. Initial experiences with combined therapy of anemia with roxadustat and epoetin α in hemodialysis patients: a case series. Pol Arch Intern Med. 2024 Sep 24:16846. doi: 10.20452/pamw.16846. Epub ahead of print. PMID: 39315513. 2: Chabannes M, Vagnet A, Benjemia L, Seibel J, Tristant M, Rabier MB, Crepin T, Ducloux D. Roxadustat, an hypoxia-inducible factor-prolyl hydroxylase inhibitor induce sickle cell crisis: A case report. Br J Haematol. 2024 Sep 18. doi: 10.1111/bjh.19783. Epub ahead of print. PMID: 39295110. 3: Bini C, Marcellusi A, Di Rienzo P, Del Vecchio L. Analisi di impatto sul budget sanitario italiano di roxadustat per il trattamento dell’anemia da malattia renale cronica. Glob Reg Health Technol Assess. 2024 Sep 10;11:175-190. Italian. doi: 10.33393/grhta.2024.3062. PMID: 39281665; PMCID: PMC11393551. 4: Shimada Y, Izumi Y, Yasuoka Y, Oshima T, Nagaba Y, Nanami M, Sands JM, Takahashi N, Kawahara K, Nonoguchi H. Renoprotective Effects of Daprodustat in Patients with Chronic Kidney Disease and Renal Anemia. Int J Mol Sci. 2024 Aug 30;25(17):9468. doi: 10.3390/ijms25179468. PMID: 39273415; PMCID: PMC11395309. 5: Shen ZW, Yang XY, Han L, Yang X, Xie J, Liu XQ, Mao JH, Dai HR, Kong WW, Wu XY, Qiu YQ, Huang HF, Lou Y. Optimizing the dosing regimen of roxadustat in kidney transplant recipients with early post-transplant anemia. J Pharm Sci. 2024 Sep 7:S0022-3549(24)00409-X. doi: 10.1016/j.xphs.2024.09.004. Epub ahead of print. PMID: 39251067. 6: Virtanen N, Saarela U, Karpale M, Arffman RK, Mäkelä KA, Herzig KH, Koivunen P, Piltonen T. Roxadustat alleviates metabolic traits in letrozole-induced PCOS mice. Biochem Pharmacol. 2024 Sep 6;229:116522. doi: 10.1016/j.bcp.2024.116522. Epub ahead of print. PMID: 39245394. 7: Kita S, Okuyama H, Kondo T, Hayashi M, Nakao S, Sawamura T, Fujimoto K, Nakagawa A, Yokoyama H, Furuichi K. Low cholesterol levels are good markers for central hypothyroidism in case with dialysis using roxadustat. Clin Case Rep. 2024 Sep 3;12(9):e9400. doi: 10.1002/ccr3.9400. PMID: 39229298; PMCID: PMC11369681. 8: Bartnicki P. Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors as a New Treatment Option for Anemia in Chronic Kidney Disease. Biomedicines. 2024 Aug 18;12(8):1884. doi: 10.3390/biomedicines12081884. PMID: 39200348; PMCID: PMC11351863. 9: Zhang LG, Ma XJ, Li XY. Case report: Roxadustat overdose in an anemia patient of chronic kidney disease: insight beyond insignificant consequence. Front Nephrol. 2024 Aug 2;4:1413496. doi: 10.3389/fneph.2024.1413496. PMID: 39155928; PMCID: PMC11327132. 10: Zhong JJ, Wang ML, Zheng GF, Li MP, Chen DZ. The clinical efficacy of combined ESA and Roxadustat treatment for renal anemia in hemodialysis patients with secondary hyperparathyroidism: A case series. Medicine (Baltimore). 2024 Aug 16;103(33):e39083. doi: 10.1097/MD.0000000000039083. PMID: 39151521; PMCID: PMC11332787. 11: Janssens LK, Stove CP. The 'ABC' of split-nanoluciferase HIF heterodimerization bioassays: Applications, Benefits & Considerations. Biochem Pharmacol. 2024 Aug 10;229:116478. doi: 10.1016/j.bcp.2024.116478. Epub ahead of print. PMID: 39128589. 12: Li N, Cui W, Mu D, Shi X, Gao L, Liu S, Wang H, Jiang C, Hu Y. Effects of roxadustat on thyroid hormone levels and blood lipid metabolism in patients undergoing hemodialysis: a retrospective study. Int J Med Sci. 2024 Jul 9;21(10):1806-1813. doi: 10.7150/ijms.97599. PMID: 39113891; PMCID: PMC11302564. 13: Zhang Y, Chen M, Tang L, Chen X, Meng Y, Feng S. A real-world analysis of roxadustat effectiveness and safety in managing renal anemia among patients on maintenance hemodialysis: An observational study. Medicine (Baltimore). 2024 Aug 2;103(31):e39203. doi: 10.1097/MD.0000000000039203. PMID: 39093766; PMCID: PMC11296405. 14: Jacquemin C, El Orch W, Diaz O, Lalande A, Aublin-Gex A, Jacolin F, Toesca J, Si-Tahar M, Mathieu C, Lotteau V, Perrin-Cocon L, Vidalain PO. Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress. Cell Mol Life Sci. 2024 Jul 30;81(1):320. doi: 10.1007/s00018-024-05361-6. PMID: 39078527; PMCID: PMC11335246. 15: Ren S, Zhao Y, Wu J, Ren S, Feng Y. Hypoxia-inducible factor-prolyl hydroxylase inhibitors for treatment of anemia in chronic kidney disease: a systematic review and network meta-analysis. Front Pharmacol. 2024 Jul 10;15:1406588. doi: 10.3389/fphar.2024.1406588. PMID: 39050745; PMCID: PMC11267515. 16: Xu Q, Huang J, Liu Q, Wang X, Liu H, Song Y, Dou F, Lv S, Liu G. Short-term effect of low-dose roxadustat combined with erythropoiesis-stimulating agent treatment for erythropoietin-resistant anemia in patients undergoing maintenance hemodialysis. Front Endocrinol (Lausanne). 2024 Jul 1;15:1372150. doi: 10.3389/fendo.2024.1372150. PMID: 39010898; PMCID: PMC11246906. 17: Zaruba MM, Staggl S, Ghadge SK, Maurer T, Gavranovic-Novakovic J, Jeyakumar V, Schönherr P, Wimmer A, Pölzl G, Bauer A, Messner M. Roxadustat Attenuates Adverse Remodeling Following Myocardial Infarction in Mice. Cells. 2024 Jun 21;13(13):1074. doi: 10.3390/cells13131074. PMID: 38994928; PMCID: PMC11240812. 18: Checkouri A, Gheddar L, Arbouche N, Raul JS, Kintz P. Simultaneous detection of three hypoxia-inducible factor stabilizers-molidustat, roxadustat, and vadadustat-in multiple keratinized matrices and its application in a doping context. Drug Test Anal. 2024 Jul 11. doi: 10.1002/dta.3771. Epub ahead of print. PMID: 38992954. 19: Omote D, Kuramoto N, Tomikawa A, Yasui M, Fukuta M, Hiraguri M. Roxadustat- Induced Central Hypothyroidism in Renal Anemia Patients: Insights From Antineutrophil Cytoplasmic Antibody-Related Vasculitis Cases. Cureus. 2024 Jun 6;16(6):e61843. doi: 10.7759/cureus.61843. PMID: 38975517; PMCID: PMC11227460. 20: Takebayashi K, Yamauchi M, Hara K, Tsuchiya T, Hashimoto K. Cerebral Infarction After Switching From Roxadustat to Daprodustat in a Patient With Renal Anemia. Cureus. 2024 Jul 6;16(7):e63942. doi: 10.7759/cureus.63942. PMID: 38974395; PMCID: PMC11227077.