Febuxostat acyl glucuronide (Febuxostat acyl-β-D-glucuronide) is a metabolite of Febuxostat. Febuxostat is a potent and specific non-purine xanthine oxidase (XO) inhibitor.

Physicochemical Properties

Molecular Formula	C22H24N2O9S
Molecular Weight	492.50
Exact Mass	492.12
Elemental Analysis	C, 53.65; H, 4.91; N, 5.69; O, 29.24; S, 6.51
CAS #	1351692-92-6
PubChem CID	71316713
Appearance	Typically exists as solid at room temperature
LogP	1.073
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	8
Heavy Atom Count	34
Complexity	790
Defined Atom Stereocenter Count	5
SMILES	CC1=C(SC(=N1)C2=CC(=C(C=C2)OCC(C)C)C#N)C(=O)OC3C(C(C(C(O3)C(=O)O)O)O)O
InChi Key	ZRXRMGPMLDOOKN-FVMGUFKOSA-N
InChi Code	InChI=1S/C22H24N2O9S/c1-9(2)8-31-13-5-4-11(6-12(13)7-23)19-24-10(3)18(34-19)21(30)33-22-16(27)14(25)15(26)17(32-22)20(28)29/h4-6,9,14-17,22,25-27H,8H2,1-3H3,(H,28,29)/t14-,15-,16+,17-,22-/m0/s1
Chemical Name	(2S,3S,4S,5R,6S)-6-[2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carbonyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
Synonyms	Febuxostat Acyl Glucuronide; 1351692-92-6; FebuxostatAcyl-beta-D-glucuronide; Febuxostat Acyl-b-D-glucuronide; (2S,3S,4S,5R,6S)-6-((2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carbonyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid; (2S,3S,4S,5R,6S)-6-[2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carbonyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid; Febuxostat Acyl-beta-D-glucuronide; 2-[3-Cyano-4-(2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylate ss-D-Glucopyranuronic Acid; 2-(3-Cyano-4-isobutyloxyphenyl)-4-methyl- 5-thiazolecarboxylate ss-D-Glucopyranuronic Acid;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Febuxostat metabolite; XO
ln Vivo	Febuxostat is a xanthine oxidoreductase inhibitor that has been developed to treat chronic gout. In healthy subjects, the pharmacokinetic parameters of febuxostat after multiple oral dose administration include an oral availability of about 85 %, an apparent oral clearance (CL/F) of 10.5 ± 3.4 L/h and an apparent volume of distribution at steady state (V ss/F) of 48 ± 23 L. The time course of plasma concentrations follows a two-compartment model. The initial half-life (t ½) is approximately 2 h and the terminal t ½ determined at daily doses of 40 mg or more is 9.4 ± 4.9 h. Febuxostat is administered once daily. The maximum (peak) plasma concentrations are approximately 100-fold greater than the trough concentrations. Consequently, there is no significant accumulation of the drug during multiple dose administration. There are few data on the pharmacokinetics of febuxostat in patients with gout. While the pharmacokinetic parameters are not affected by mild to moderate hepatic impairment, there is no consensus on whether renal impairment has any effect on the pharmacokinetics of febuxostat. Febuxostat is extensively metabolised by oxidation (approximately 35 %) and acyl glucuronidation (up to 40 %); febuxostat acyl glucuronides are cleared by the kidney. In healthy subjects treated with multiple doses of febuxostat 10-240 mg, the concentrations of serum urate are reduced by a maximum of about 80 %. The percentage reduction in the concentrations of serum urate is slightly less in gouty patients than in healthy subjects [1].
References	[1]. Clinical Pharmacokinetics and Pharmacodynamics of Febuxostat. Clin Pharmacokinet. 2017 May;56(5):459-475.
Additional Infomation	Background: Osteoarthritis (OA) is a disease commonly diagnosed in the elderly population. It is reported that the reduction of extracellular matrix and infiltrated inflammation are two main factors responsible for the pathogenesis of OA. This investigation aims to explore the potential protective effects of Febuxostat against IL-18-induced insults in chondrocytes, as well as the possible mechanism. Materials and methods: The viability of chondrocytes was evaluated using the MTT assay. QRT-PCR and ELISA were used to measure the expressions and concentrations of IL-6, TNF-α, and CCL5, respectively. The accumulation of glycosaminoglycans (GAGs) was measured using Alcian blue assay. The chondrocytes were transfected with siRNA against Sox-9 in order to establish the Sox-9 knock-down chondrocytes. The expressions of iNOS, Col2a1, Acan, and Sox-9 were measured using qRT-PCR. The production of NO was measured using Diaminofluorescein-FM diacetate (DAF-FM DA) staining. Results: The up-regulated expressions of IL-6, TNF-α, CCL5, iNOS, and NO stimulated by IL-18 were down-regulated by the introduction of Febuxostat. The expressions of Col2a1, Acan, and Sox-9 were significantly reduced by IL-18 but greatly promoted by Febuxostat. The increased gene expressions of Col2a1 and Acan induced by Febuxostat were abolished by knocking down Sox-9 in the chondrocytes. Conclusion: Febuxostat might mitigate IL-18-induced inflammatory response and reduction of the extracellular matrix gene mediated by Sox-9. https://pmc.ncbi.nlm.nih.gov/articles/PMC8014396/

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0305 mL	10.1523 mL	20.3046 mL
	5 mM	0.4061 mL	2.0305 mL	4.0609 mL
	10 mM	0.2030 mL	1.0152 mL	2.0305 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.