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Chemical Structure| 577778-58-6 Chemical Structure| 577778-58-6

Structure of Topiroxostat
CAS No.: 577778-58-6

Chemical Structure| 577778-58-6

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Topiroxostat is an inhibitor of xanthine oxidoreductase (XOR) with IC50 of 5.3 nM.

Synonyms: FYX-051

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Product Details of Topiroxostat

CAS No. :577778-58-6
Formula : C13H8N6
M.W : 248.24
SMILES Code : N#CC1=NC=CC(C2=NC(C3=CC=NC=C3)=NN2)=C1
Synonyms :
FYX-051
MDL No. :MFCD17167057
InChI Key :UBVZQGOVTLIHLH-UHFFFAOYSA-N
Pubchem ID :5288320

Safety of Topiroxostat

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Human kidney proximal tubule epithelial cells (HK-2 cells) 5 or 10 µM 1 hour To investigate the effects of XO inhibition on LDL-induced oxidative stress and cholesterol synthesis. Results showed that TP reduced LDL-induced cellular ROS, similar to the positive control NAC. Int J Mol Sci. 2020 Oct 9;21(20):7444

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice High HPRT activity –Uox knockout mice Dietary administration 1 mg/kg Once daily for 7 days Evaluate the effect of topiroxostat on urate metabolism, significantly reduced plasma urate levels and urinary urate/creatinine ratio without affecting HPRT activity Br J Pharmacol. 2020 May;177(10):2274-2285
Rats SU5416/hypoxia/normoxia-induced pulmonary hypertension model Admixed in diet 1 mg/kg Started from the day of SU5416 injection to week 5 To investigate the effect of Topiroxostat on pulmonary arterial hypertension, results showed that Topiroxostat significantly reduced lung XOR activity in PAH rats, with no effects on increase in right ventricular systolic pressure, arterial elastance, and occlusive lesions. J Am Heart Assoc. 2021 Dec 7;10(23):e022712
ApoE knockout mice Uninephrectomy-induced chronic kidney disease (CKD) model Oral gavage 1 mg/kg/day Once daily for 4 weeks To investigate the effects of XO inhibition on high-cholesterol diet-induced renal dysfunction. Results showed that TP attenuated hypercholesterolemia-associated renal dysfunction, reduced kidney cholesterol accumulation and oxidative stress. Int J Mol Sci. 2020 Oct 9;21(20):7444
C57BL/6J mice Nonobese NAFLD/NASH model Drug-admixed food method 1 mg/kg/day Once daily for 3 weeks To investigate the inhibitory effect of topiroxostat on vascular neointima formation in NAFLD/NASH mice. Results showed that topiroxostat significantly suppressed plasma XOR activity and attenuated neointima formation induced by carotid artery ligation. JCI Insight. 2021 Sep 8;6(17):e144762
Rats Renal ischemia-reperfusion injury model Oral 10 mg/kg Single dose, 60 min before surgery To evaluate the protective effects of Topiroxostat on renal ischemia-reperfusion injury, results showed that Topiroxostat increased renal concentrations of high-energy phosphates and reduced depletion of adenine compounds. Mol Med. 2019 Aug 22;25(1):40
Mice Diabetic obese model Oral 3 mg/kg/day Once daily for 4 weeks To investigate the effect of topiroxostat on body weight. Results showed that topiroxostat suppressed weight gain without affecting food intake, decreased plasma uric acid and liver XOR activity, and increased hepatic hypoxanthine and plasma ketone bodies and free fatty acids. Nutr Diabetes. 2021 Apr 13;11(1):12

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

4.03mL

0.81mL

0.40mL

20.14mL

4.03mL

2.01mL

40.28mL

8.06mL

4.03mL

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