Topiroxostat

Topiroxostat Properties

Boiling point	594.7±60.0 °C(Predicted)
Density	1.45±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO : 23.5 mg/mL (94.67 mM; Need ultrasonic and warming)
form	Powder
pka	7.47±0.10(Predicted)
color	White to off-white
InChI	InChI=1S/C13H8N6/c14-8-11-7-10(3-6-16-11)13-17-12(18-19-13)9-1-4-15-5-2-9/h1-7H,(H,17,18,19)
InChIKey	UBVZQGOVTLIHLH-UHFFFAOYSA-N
SMILES	C1(C#N)=NC=CC(C2NN=C(C3C=CN=CC=3)N=2)=C1

SAFETY

Risk and Safety Statements

Symbol(GHS)

GHS07

Signal word

Warning

Hazard statements

H315-H319-H335

Precautionary statements

P261-P305+P351+P338

NFPA 704

	0
2		0

Topiroxostat Chemical Properties,Uses,Production

Description

Topiroxostat is an orally-administered, non-purine, selective xanthine oxidase (XO) inhibitor developed for the treatment of hyperuricemia specifically for patients with gout in Japan. The drug was discovered and developed by Fuji Yakuhin. In contrast to conventional XO inhibitors such as febuxostat, topiroxostat interacts with key amino acid residues of the solvent channel.

Chemical Properties

Topiroxostat is soluble in organic solvents such as DMSO and dimethyl formamide (DMF). The solubility of topiroxostat in these solvents is approximately 10 and 20 mg/ml, respectively.

Uses

Topiroxostat is a selective xanthine oxidase inhibitor developed for treatment and management of hyperuricemia and gout. Xanthine oxidase, or xanthine oxidoreductase (XOR), regulates purine metabolism, and inhibition of the enzyme results in efficacious reduction of serum urate levels. Approved for therapeutic use in Japan since 2013, topiroxostat is marketed under the name Topiloric and Uriadec and is orally administered twice daily.

Biological Activity

Topiroxostat is an inhibitor of xanthine oxidoreductase (IC50 = 5.3 nM), an enzyme that converts xanthine to urate. Formulations containing topiroxostat are effective in vivo, lowering urate levels in the serum of patients with hyperuricemia. In rats, but not primates, topiroxostat treatment results in the formation of xanthine crystals, resulting in nephritis. Topiroxostat also inhibits ATP-binding cassette transporter G2 (ABCG2; IC50 = 0.18 μM), a high-capacity urate transporter that functions in both renal and extrarenal urate secretion.

Pharmacology

Topiroxostat is a novel inhibitor of xanthine oxidase, and is postulated to exert a renoprotective effect. Puromycin aminonucleoside nephrosis (PAN) is a rat model of minimal change nephrotic syndrome. In this study, we examined whether topiroxostat ameliorates the kidney injury in PAN rats that was induced by a single intraperitoneal injection of PA (100mg/kg body weight). Rats were divided into four groups: control rats, PAN rats, control rats treated with topiroxostat (1.0mg/kg/day), and PAN rats treated with topiroxostat. Topiroxostat significantly reduced the amount of uric acid in the kidney cortex, while serum UA concentration remained unaffected by this treatment. Urinary protein excretion decreased significantly on day 10 in PAN rats upon topiroxostat treatment. Podocyte injury in PAN rats, as indicated by the reduction in WT‐1‐positive cell numbers and podocin immunoreactivity and foot process effacement, was partially yet significantly alleviated with topiroxostat treatment. In the kidney cortex, the increase in oxidative stress markers such as nitrotyrosine and 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG) and the enhanced expressions of xanthine oxidase and NADPH oxidase 4 (NOX4) in PAN rats were significantly ameliorated by topiroxostat. Using cultured podocytes NOX4 expression was upregulated by adding 12mg/dL UA into the culture medium. These results suggest that topiroxostat ameliorates proteinuria and kidney injury in PAN rats by lowering oxidative stress and tissue UA concentration. The renoprotective effects of topiroxostat could be attributed to its potential to inhibit xanthine oxidase and NOX4 in concert with suppression of intracellular UA production. Abstract : Topiroxostat ameliorates proteinuria and renal injury independently of serum UA level in PAN‐induced nephrotic rats. Topiroxostat exerts a renoprotective effect owing to its antioxidant effects and property to lower UA levels in the kidney cortex.

Clinical Use

Topiroxostat, a novel XO inhibitor, ameliorated proteinuria in association with podocyte injury markers such as decrease in WT-1 and podocin expressions and foot process effacement on electron microscope.

Topiroxostat Preparation Products And Raw materials

Raw materials

Preparation Products

Topiroxostat Suppliers

Global( 353)Suppliers

Supplier	Tel	Country	ProdList	Advantage	Inquiry
Precise Biopharma Pvt Ltd	+91-2267828600 +91-2267828600	Maharashtra, India	46	58	Inquiry
SynZeal Research Pvt Ltd	+1 226-802-2078	Gujarat, India	6522	58	Inquiry
A.J Chemicals	91-9810153283	New Delhi, India	6124	58	Inquiry
CLEARSYNTH LABS LTD.	+91-22-45045900	Hyderabad, India	6351	58	Inquiry
Shandong Hengshannuode Pharmaceutical Technology Co., Ltd.	+8615065888978	China	92	58	Inquiry
TAIZHOU YUXIN BIOTECHNOLOGY CO,.LTD	+86-576-88902229;+86-0576-88902229 +8613968687450	China	158	58	Inquiry
Hangzhou ICH Biofarm Co., Ltd	+86-0571-28186870; +undefined8613073685410	China	998	58	Inquiry
Shaanxi Dideu Medichem Co. Ltd	+86-29-81148696 +86-15536356810	China	3878	58	Inquiry
shandong perfect biotechnology co.ltd	+86-53169958659; +8618596095638	China	294	58	Inquiry
Henan Bao Enluo International TradeCo.，LTD	+86-17331933971 +86-17331933971	China	2503	58	Inquiry

Supplier	Advantage
Precise Biopharma Pvt Ltd	58
SynZeal Research Pvt Ltd	58
A.J Chemicals	58
CLEARSYNTH LABS LTD.	58
Shandong Hengshannuode Pharmaceutical Technology Co., Ltd.	58
TAIZHOU YUXIN BIOTECHNOLOGY CO,.LTD	58
Hangzhou ICH Biofarm Co., Ltd	58
Shaanxi Dideu Medichem Co. Ltd	58
shandong perfect biotechnology co.ltd	58
Henan Bao Enluo International TradeCo.，LTD	58

Topiroxostat Spectrum

Topiroxostat(577778-58-6)¹HNMR

577778-58-6(Topiroxostat)Related Search:

Topiroxostat Impurity 2 2-Cyano-N'-(imino(pyridin-4-yl)methyl)isonicotinohydrazide 2-CARBAMOYL-ISONICOTINIC ACID ETHYL ESTER 4-PYRIDINECARBOXIMIDIC ACID, HYDRAZIDE Topiroxostat Impurity 23

Pyridine, 4-[5-(4-pyridinyl)-1H-1,2,4-triazol-3-yl]-, 1-oxide METHYLISONICOTINATE-N-OXIDE Topiroxostat Impurity 5 2-CYANO-4-PYRIDINE CARBOXYLIC ACID METHYL ESTER Methyl nicotinate

2-CYANO-4-PYRIDINE CARBOXYLIC ACID Topiroxostat Impurity 6 4-Pyridinecarboxylicacid,2-cyano-,hydrazide(9CI) Topiroxostat Impurity 15 VILAZODONE

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FYX 051 Topiroxostat Topiroxostat,FYX-051 5-(2-Cyano-4-pyridyl)-3-(4-pyridyl)-1,2,4-triazole Topiroxostat 5-(2-Cyano-4-pyridyl)-3-(4-pyridyl)-1,2,4-triazole 4-[5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile 2-Pyridinecarbonitrile, 4-[5-(4-pyridinyl)-1H-1,2,4-triazol-3-yl]- Topiroxostat impurty Topiroxostat C13H8N6 high quality Cas number：577778-58-6 4-(3-(Pyridin-4-yl)-1H-1,2,4-triazol-5-yl)picolinonitrile [14C]-Topiroxostat 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole Factory supply Topiroxostat Cas 577778-58-6 with high quality and best price FYX-051; FYX051; FYX 051; TOPIROXOSTAT. TRADE NAMES TOPILORIC; URIADEC. Topiroxostat. trade names Topiloric Uriadec. CS-1334 4-(5-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyridine-2-carbonitrile 4-[5-(4-Pyridyl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile Toby Starr 4-(3-(Pyridin-4-yL inonitriL 2-Pyridinecarbonitrile, 4-[3-(4-pyridinyl)-1H-1,2,4-triazol-5-yl]- Topiroxosta Topicast impurity N-desmethyl N-Nitroso Topotecan-D3 577778-58-6 577779-58-6 Inhibitors API 577778-58-6