Identification

Name
Topiroxostat
Accession Number
DB01685  (EXPT01517)
Type
Small Molecule
Groups
Approved, Investigational
Description

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. Xanthine oxidase inhibitors are classified into two groups; purine analogs such as Allopurinol and Oxypurinol, and non-purine agents which includes topiroxostat. While Allopurinol is considered a first-line therapy in treating hyperuricemic conditions, it is often associated with side effects and ineffective in reducing uric acid levels under recommended dosing regimens. Renal complications are major comorbidities that limit the Allopurinol therapy as dose reductions are recommended. Topiroxostat and its metabolites are shown to be unaffected by renal complications, thus may be effective in patients with chronic kidney diseases [2]. Approved for therapeutic use in Japan since 2013, topiroxostat is marketed under the name Topiloric and Uriadec and is orally administered twice daily.

Structure
Thumb
Synonyms
  • 4-(5-(pyridin-4-yl)-1H-1,2,4-triazol-3-yl)pyridine-2-carbonitrile
External IDs
FYX-051
International/Other Brands
Topiloric (Fujiyakuhin Co.) / Uriadec (Sanwa Kagaku Kenkyusho Co.)
Categories
UNII
0J877412JV
CAS number
577778-58-6
Weight
Average: 248.2428
Monoisotopic: 248.081044286
Chemical Formula
C13H8N6
InChI Key
UBVZQGOVTLIHLH-UHFFFAOYSA-N
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)
IUPAC Name
4-[5-(pyridin-4-yl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile
SMILES
N#CC1=NC=CC(=C1)C1=NNC(=N1)C1=CC=NC=C1

Pharmacology

Indication

Indicated for the treatment of gout and hyperurcemia in Japan.

Structured Indications
Not Available
Pharmacodynamics

Topiroxostat reduces the synthesis of uric acid by competitively inhibiting xanthine oxidase in a selective and time-dependent manner [1]. It serves to reduce the concentration of insoluble urates and uric acid in tissues, plasma and urine. Topiroxostat is not reported to cause QT prolongation [4].

Mechanism of action

Uric acid synthesis depends on the action of xanthine oxidase activity in the conversion of hypoxanthine to xanthine, followed by the conversion of xanthine to uric acid. Xanthine oxidase consists of a molybdenum ion as cofactor in the active center that has different redox states upon substrate binding [9]. When a substrate such as hypoxanthine or xanthine binds, xanthine oxidase hydroxylates it and molybdenum ion is reduced from hexavalent, Mo(VI), to tetravalent form, Mo(IV). Molybdenum ion is reoxidized into hexavalent state once the hydroxylated substrate, xanthine or uric acid, dissociates from the active site. Topiroxostat is shown to interact with multiple amino acid residues of the solvent channel and additionally forms a reaction intermediate by covalent binding with molybdenum (IV) ion via an oxygen atom [2, 9, 5, 6]. It also forms hydrogen bonds with molybdenum (VI) ion, suggesting that it has multiple inhibition modes to xanthine oxidase [9]. Enhanced binding interactions to xanthine oxidase achieves delayed dissociation of topiroxostat from the enzyme. 2-hydroxy-topiroxostat, the metabolite formed by primary hydroxylation of topiroxostat by xanthine oxidase, also causes time and concentration-dependent inhibition of the enzyme [1]. Topiroxostat is shown to inhibit ATP-binding cassette transporter G2 (ABCG2) in vitro, which is a membrane protein responsible for recovering uric acid in the kidneys and secreting uric acid from the intestines [3].

TargetActionsOrganism
UXanthine dehydrogenase/oxidaseNot AvailableHuman
Absorption

The time to reach peak plasma concentration of 229.9 ng/mL was 0.67 hour following a single oral dose of 20mg topiroxostat [9]. The oral bioavailability in male rats was 69.6% after oral administration of a single dose of 1mg/kg [9].

Volume of distribution

The distribution of 14C-topiroxostat (20, 200, and 2000 ng/mL) in human blood cells was 6.7% to 12.8% [9].

Protein binding

The mean protein binding of radiolabeled (14C)-topiroxostat in human plasma is >97.5% at 20ng/mL, 98.8% at 200ng/mL, and 98.4% at 2000ng/mL. Binding to serum albumin is most predominant with 92.3-93.2%, and mean protein binding to α1-acid protein and γ-globulin is 12.3% to 16.8% and 34.7% to 40.4%, respectively [9].

Metabolism

Topiroxostat is mainly inactivated by hepatic metabolism. 2-hydroxy topiroxostat is formed from primary hydroxylation of the drug by xanthine oxidase and still retains an inhibitory activity on the enzyme [1]. Topiroxostat N-oxide is another major metabolite that can be detected in plasma and urine. It is determined that the N-oxide and hydroxide metabolites are pyridine N-oxide and pyridine 2 (or 6)-hydroxide, respectively [7]. Topiroxostat is mainly inactivated by hepatic metabolism where it undergoes glucuronidation. The metabolism of topiroxostat to N1-and N2-glucuronide conjugates is mainly mediated by UGT1A1, 1A7, and 1A9, with UGT1A9 being the most predominant [9].

Route of elimination

Urinary excretion and fecal excretion of radiolabeled topiroxostat are 30.4% and 40.9% of total dose of 1mg/kg administered to rats, respectively. Within 24 h after a single oral administration of 120mg of topiroxostat, the main metabolites of topiroxostat, N-oxide, N1-gluculonide, and N2-gluculonide, are excreted into urine about 4.8, 43.3, and 16.1 % of the dose, respectively. Unchanged topiroxostat and the hydroxide metabolite was 0.1% or less [7].

Half life

The mean half life of topiroxostat after a single oral dose of 20mg topiroxostat is 5 hours under fasting condition. The complex of molybdenum (IV)- topiroxostat has an approximate half life of 20.4 hours [9].

Clearance

The apparent total body clearance rate is 89.5 L/h and the renal clearance rate is 17.4 mL/h following a single oral dose of 20mg topiroxostat [9].

Toxicity

Topiroxostat is not reported to be carcinogenic, genotoxic, or teratogenic [9]. Some reported adverse events of topiroxostat therapy include nasopharyngitis, pain in extremity, elevated alanine aminotransferase (ALT), decreased white blood cell count, eczema and gout arthritis. The no-observed-adverse-effect-level (NOAEL) was determined to be ≥300 mg/kg/day in a study of once-daily, 52-week oral administration of 0/10/30/100 mg/kg/day topiroxostat in monkeys [9].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Topiroxostat.Approved, Investigational
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Topiroxostat.Approved
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Topiroxostat.Approved
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Topiroxostat.Approved, Vet Approved
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Topiroxostat.Approved, Investigational
AlosetronThe metabolism of Alosetron can be decreased when combined with Topiroxostat.Approved, Withdrawn
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Topiroxostat.Approved, Illicit, Investigational
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Topiroxostat.Approved, Withdrawn
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Topiroxostat.Approved, Investigational
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Topiroxostat.Approved
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Topiroxostat.Approved, Investigational
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Topiroxostat.Approved
AntipyrineThe metabolism of Antipyrine can be decreased when combined with Topiroxostat.Approved
ApixabanThe metabolism of Apixaban can be decreased when combined with Topiroxostat.Approved
Arachidonic AcidThe metabolism of Arachidonic Acid can be decreased when combined with Topiroxostat.Experimental
ArformoterolThe metabolism of Arformoterol can be decreased when combined with Topiroxostat.Approved, Investigational
ArtemetherThe metabolism of Artemether can be decreased when combined with Topiroxostat.Approved
AtazanavirThe metabolism of Atazanavir can be decreased when combined with Topiroxostat.Approved, Investigational
AtorvastatinThe risk or severity of adverse effects can be increased when Topiroxostat is combined with Atorvastatin.Approved
AzelastineThe metabolism of Azelastine can be decreased when combined with Topiroxostat.Approved
Benzyl alcoholThe metabolism of Benzyl alcohol can be decreased when combined with Topiroxostat.Approved
BeraprostThe metabolism of Beraprost can be decreased when combined with Topiroxostat.Investigational
BexaroteneThe metabolism of Bexarotene can be decreased when combined with Topiroxostat.Approved, Investigational
BortezomibThe metabolism of Bortezomib can be decreased when combined with Topiroxostat.Approved, Investigational
BosentanThe serum concentration of Bosentan can be increased when it is combined with Topiroxostat.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Topiroxostat.Approved
BrivaracetamThe metabolism of Brivaracetam can be decreased when combined with Topiroxostat.Approved, Investigational
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Topiroxostat.Approved, Investigational
BrompheniramineThe metabolism of Brompheniramine can be decreased when combined with Topiroxostat.Approved
BuprenorphineThe metabolism of Buprenorphine can be decreased when combined with Topiroxostat.Approved, Illicit, Investigational, Vet Approved
BupropionThe metabolism of Bupropion can be decreased when combined with Topiroxostat.Approved
CabazitaxelThe metabolism of Cabazitaxel can be decreased when combined with Topiroxostat.Approved
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Topiroxostat.Approved
CabozantinibThe metabolism of Cabozantinib can be decreased when combined with Topiroxostat.Approved
CaffeineThe metabolism of Caffeine can be decreased when combined with Topiroxostat.Approved
CandesartanThe metabolism of Candesartan can be decreased when combined with Topiroxostat.Experimental
Candesartan cilexetilThe metabolism of Candesartan cilexetil can be decreased when combined with Topiroxostat.Approved
CarbamazepineThe metabolism of Carbamazepine can be decreased when combined with Topiroxostat.Approved, Investigational
CarbinoxamineThe metabolism of Carbinoxamine can be decreased when combined with Topiroxostat.Approved
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Topiroxostat.Approved, Investigational
CelecoxibThe metabolism of Celecoxib can be decreased when combined with Topiroxostat.Approved, Investigational
CerivastatinThe metabolism of Cerivastatin can be decreased when combined with Topiroxostat.Withdrawn
ChloroquineThe metabolism of Chloroquine can be decreased when combined with Topiroxostat.Approved, Vet Approved
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Topiroxostat.Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Topiroxostat.Approved
CinnarizineThe metabolism of Cinnarizine can be decreased when combined with Topiroxostat.Approved, Investigational
CisaprideThe metabolism of Cisapride can be decreased when combined with Topiroxostat.Approved, Investigational, Withdrawn
ClopidogrelThe metabolism of Clopidogrel can be decreased when combined with Topiroxostat.Approved, Nutraceutical
ClozapineThe metabolism of Clozapine can be decreased when combined with Topiroxostat.Approved
CyclophosphamideThe metabolism of Cyclophosphamide can be decreased when combined with Topiroxostat.Approved, Investigational
DabrafenibThe metabolism of Dabrafenib can be decreased when combined with Topiroxostat.Approved
DapagliflozinThe metabolism of Dapagliflozin can be decreased when combined with Topiroxostat.Approved
DapsoneThe metabolism of Dapsone can be decreased when combined with Topiroxostat.Approved, Investigational
DasabuvirThe metabolism of Dasabuvir can be decreased when combined with Topiroxostat.Approved
DextromethorphanThe metabolism of Dextromethorphan can be decreased when combined with Topiroxostat.Approved
DiazepamThe metabolism of Diazepam can be decreased when combined with Topiroxostat.Approved, Illicit, Vet Approved
DiclofenacThe metabolism of Diclofenac can be decreased when combined with Topiroxostat.Approved, Vet Approved
DicoumarolThe metabolism of Dicoumarol can be decreased when combined with Topiroxostat.Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Topiroxostat.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Topiroxostat.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Topiroxostat.Experimental
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Topiroxostat.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Topiroxostat.Approved
DiphenhydramineThe metabolism of Diphenhydramine can be decreased when combined with Topiroxostat.Approved
DoconexentThe metabolism of Doconexent can be decreased when combined with Topiroxostat.Approved, Investigational
DolasetronThe metabolism of Dolasetron can be decreased when combined with Topiroxostat.Approved
DomperidoneThe metabolism of Domperidone can be decreased when combined with Topiroxostat.Approved, Investigational, Vet Approved
DonepezilThe metabolism of Donepezil can be decreased when combined with Topiroxostat.Approved
DopamineThe metabolism of Dopamine can be decreased when combined with Topiroxostat.Approved
DorzolamideThe metabolism of Dorzolamide can be decreased when combined with Topiroxostat.Approved
DoxepinThe metabolism of Doxepin can be decreased when combined with Topiroxostat.Approved
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Topiroxostat.Approved, Illicit
EletriptanThe metabolism of Eletriptan can be decreased when combined with Topiroxostat.Approved, Investigational
EltrombopagThe metabolism of Eltrombopag can be decreased when combined with Topiroxostat.Approved
EnasidenibThe metabolism of Enasidenib can be decreased when combined with Topiroxostat.Approved
EnzalutamideThe metabolism of Enzalutamide can be decreased when combined with Topiroxostat.Approved
EpoprostenolThe metabolism of Epoprostenol can be decreased when combined with Topiroxostat.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Topiroxostat.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Topiroxostat.Approved
ErlotinibThe metabolism of Erlotinib can be decreased when combined with Topiroxostat.Approved, Investigational
EstradiolThe metabolism of Estradiol can be decreased when combined with Topiroxostat.Approved, Investigational, Vet Approved
EstroneThe metabolism of Estrone can be decreased when combined with Topiroxostat.Approved
EszopicloneThe metabolism of Eszopiclone can be decreased when combined with Topiroxostat.Approved
EtodolacThe metabolism of Etodolac can be decreased when combined with Topiroxostat.Approved, Investigational, Vet Approved
EtoricoxibThe metabolism of Etoricoxib can be decreased when combined with Topiroxostat.Approved, Investigational
EtravirineThe metabolism of Etravirine can be decreased when combined with Topiroxostat.Approved
FlunarizineThe metabolism of Flunarizine can be decreased when combined with Topiroxostat.Approved
FlunitrazepamThe metabolism of Flunitrazepam can be decreased when combined with Topiroxostat.Approved, Illicit
FluorouracilThe metabolism of Fluorouracil can be decreased when combined with Topiroxostat.Approved
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Topiroxostat.Approved, Vet Approved
FlurbiprofenThe metabolism of Flurbiprofen can be decreased when combined with Topiroxostat.Approved, Investigational
FluvastatinThe metabolism of Fluvastatin can be decreased when combined with Topiroxostat.Approved
FormoterolThe metabolism of Formoterol can be decreased when combined with Topiroxostat.Approved, Investigational
FosphenytoinThe metabolism of Fosphenytoin can be decreased when combined with Topiroxostat.Approved
GavestinelThe metabolism of Gavestinel can be decreased when combined with Topiroxostat.Investigational
GliclazideThe metabolism of Gliclazide can be decreased when combined with Topiroxostat.Approved
GlimepirideThe metabolism of Glimepiride can be decreased when combined with Topiroxostat.Approved
GlipizideThe metabolism of Glipizide can be decreased when combined with Topiroxostat.Approved
GlyburideThe metabolism of Glyburide can be decreased when combined with Topiroxostat.Approved
GuanfacineThe metabolism of Guanfacine can be decreased when combined with Topiroxostat.Approved, Investigational
HalofantrineThe metabolism of Halofantrine can be decreased when combined with Topiroxostat.Approved
HaloperidolThe metabolism of Haloperidol can be decreased when combined with Topiroxostat.Approved
HalothaneThe metabolism of Halothane can be decreased when combined with Topiroxostat.Approved, Vet Approved
HexobarbitalThe metabolism of Hexobarbital can be decreased when combined with Topiroxostat.Approved
HistamineThe metabolism of Histamine can be decreased when combined with Topiroxostat.Approved, Investigational
HydromorphoneThe metabolism of Hydromorphone can be decreased when combined with Topiroxostat.Approved, Illicit
IbuprofenThe metabolism of Ibuprofen can be decreased when combined with Topiroxostat.Approved
IdarubicinThe metabolism of Idarubicin can be decreased when combined with Topiroxostat.Approved
IfosfamideThe metabolism of Ifosfamide can be decreased when combined with Topiroxostat.Approved
ImatinibThe metabolism of Imatinib can be decreased when combined with Topiroxostat.Approved
indisulamThe metabolism of indisulam can be decreased when combined with Topiroxostat.Investigational
IndomethacinThe metabolism of Indomethacin can be decreased when combined with Topiroxostat.Approved, Investigational
IrbesartanThe metabolism of Irbesartan can be decreased when combined with Topiroxostat.Approved, Investigational
IxazomibThe metabolism of Ixazomib can be decreased when combined with Topiroxostat.Approved
KetamineThe metabolism of Ketamine can be decreased when combined with Topiroxostat.Approved, Vet Approved
KetobemidoneThe metabolism of Ketobemidone can be decreased when combined with Topiroxostat.Approved, Investigational
KetoprofenThe metabolism of Ketoprofen can be decreased when combined with Topiroxostat.Approved, Vet Approved
LansoprazoleThe metabolism of Lansoprazole can be decreased when combined with Topiroxostat.Approved, Investigational
LapatinibThe metabolism of Lapatinib can be decreased when combined with Topiroxostat.Approved, Investigational
LeflunomideThe metabolism of Leflunomide can be decreased when combined with Topiroxostat.Approved, Investigational
LesinuradThe metabolism of Lesinurad can be decreased when combined with Topiroxostat.Approved
LevomilnacipranThe metabolism of Levomilnacipran can be decreased when combined with Topiroxostat.Approved
LicofeloneThe metabolism of Licofelone can be decreased when combined with Topiroxostat.Investigational
LidocaineThe metabolism of Lidocaine can be decreased when combined with Topiroxostat.Approved, Vet Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Topiroxostat.Approved, Investigational
LoperamideThe metabolism of Loperamide can be decreased when combined with Topiroxostat.Approved
LoratadineThe metabolism of Loratadine can be decreased when combined with Topiroxostat.Approved
LornoxicamThe metabolism of Lornoxicam can be decreased when combined with Topiroxostat.Approved, Investigational
LosartanThe metabolism of Losartan can be decreased when combined with Topiroxostat.Approved
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Topiroxostat.Approved, Investigational
LumiracoxibThe metabolism of Lumiracoxib can be decreased when combined with Topiroxostat.Approved, Investigational
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Topiroxostat.Illicit, Investigational, Withdrawn
Mefenamic acidThe metabolism of Mefenamic acid can be decreased when combined with Topiroxostat.Approved
MelatoninThe metabolism of Melatonin can be decreased when combined with Topiroxostat.Approved, Nutraceutical, Vet Approved
MeloxicamThe metabolism of Meloxicam can be decreased when combined with Topiroxostat.Approved, Vet Approved
MephenytoinThe metabolism of Mephenytoin can be decreased when combined with Topiroxostat.Investigational, Withdrawn
MestranolThe metabolism of Mestranol can be decreased when combined with Topiroxostat.Approved
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Topiroxostat.Experimental
MethadoneThe metabolism of Methadone can be decreased when combined with Topiroxostat.Approved
MethoxyfluraneThe metabolism of Methoxyflurane can be decreased when combined with Topiroxostat.Approved, Investigational, Vet Approved
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Topiroxostat.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Topiroxostat.Approved
MetronidazoleThe metabolism of Metronidazole can be decreased when combined with Topiroxostat.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Topiroxostat.Experimental
MirtazapineThe metabolism of Mirtazapine can be decreased when combined with Topiroxostat.Approved
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Topiroxostat.Approved
MontelukastThe metabolism of Montelukast can be decreased when combined with Topiroxostat.Approved
MorphineThe metabolism of Morphine can be decreased when combined with Topiroxostat.Approved, Investigational
muraglitazarThe metabolism of muraglitazar can be decreased when combined with Topiroxostat.Investigational
Mycophenolate mofetilThe metabolism of Mycophenolate mofetil can be decreased when combined with Topiroxostat.Approved, Investigational
NaloxoneThe metabolism of Naloxone can be decreased when combined with Topiroxostat.Approved, Vet Approved
NaproxenThe metabolism of Naproxen can be decreased when combined with Topiroxostat.Approved, Vet Approved
NateglinideThe metabolism of Nateglinide can be decreased when combined with Topiroxostat.Approved, Investigational
NetupitantThe metabolism of Netupitant can be decreased when combined with Topiroxostat.Approved
NevirapineThe metabolism of Nevirapine can be decreased when combined with Topiroxostat.Approved
NicardipineThe metabolism of Nicardipine can be decreased when combined with Topiroxostat.Approved
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Topiroxostat.Approved, Investigational
NiclosamideThe metabolism of Niclosamide can be decreased when combined with Topiroxostat.Approved, Investigational, Vet Approved
NicotineThe metabolism of Nicotine can be decreased when combined with Topiroxostat.Approved
NortriptylineThe metabolism of Nortriptyline can be decreased when combined with Topiroxostat.Approved
OdanacatibThe metabolism of Odanacatib can be decreased when combined with Topiroxostat.Investigational
OlodaterolThe metabolism of Olodaterol can be decreased when combined with Topiroxostat.Approved
OmbitasvirThe metabolism of Ombitasvir can be decreased when combined with Topiroxostat.Approved
OmeprazoleThe metabolism of Omeprazole can be decreased when combined with Topiroxostat.Approved, Investigational, Vet Approved
OndansetronThe metabolism of Ondansetron can be decreased when combined with Topiroxostat.Approved
OspemifeneThe metabolism of Ospemifene can be decreased when combined with Topiroxostat.Approved
OxaprozinThe metabolism of Oxaprozin can be decreased when combined with Topiroxostat.Approved
PaclitaxelThe metabolism of Paclitaxel can be decreased when combined with Topiroxostat.Approved, Vet Approved
ParamethadioneThe metabolism of Paramethadione can be decreased when combined with Topiroxostat.Approved
ParecoxibThe metabolism of Parecoxib can be decreased when combined with Topiroxostat.Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Topiroxostat.Approved
PentamidineThe metabolism of Pentamidine can be decreased when combined with Topiroxostat.Approved
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Topiroxostat.Approved, Investigational, Vet Approved, Withdrawn
PerospironeThe metabolism of Perospirone can be decreased when combined with Topiroxostat.Approved
PerphenazineThe metabolism of Perphenazine can be decreased when combined with Topiroxostat.Approved
PhenacetinThe metabolism of Phenacetin can be decreased when combined with Topiroxostat.Withdrawn
PhenobarbitalThe metabolism of Phenobarbital can be decreased when combined with Topiroxostat.Approved
PhenprocoumonThe metabolism of Phenprocoumon can be decreased when combined with Topiroxostat.Approved, Investigational
PhenylbutazoneThe metabolism of Phenylbutazone can be decreased when combined with Topiroxostat.Approved, Vet Approved
PhenytoinThe metabolism of Phenytoin can be decreased when combined with Topiroxostat.Approved, Vet Approved
PioglitazoneThe metabolism of Pioglitazone can be decreased when combined with Topiroxostat.Approved, Investigational
PiroxicamThe metabolism of Piroxicam can be decreased when combined with Topiroxostat.Approved, Investigational
PitavastatinThe metabolism of Pitavastatin can be decreased when combined with Topiroxostat.Approved
PonatinibThe metabolism of Ponatinib can be decreased when combined with Topiroxostat.Approved
PrasugrelThe metabolism of Prasugrel can be decreased when combined with Topiroxostat.Approved
PravastatinThe metabolism of Pravastatin can be decreased when combined with Topiroxostat.Approved
ProgesteroneThe metabolism of Progesterone can be decreased when combined with Topiroxostat.Approved, Vet Approved
ProguanilThe metabolism of Proguanil can be decreased when combined with Topiroxostat.Approved
PromazineThe metabolism of Promazine can be decreased when combined with Topiroxostat.Approved, Vet Approved
PropofolThe metabolism of Propofol can be decreased when combined with Topiroxostat.Approved, Investigational, Vet Approved
QuazepamThe metabolism of Quazepam can be decreased when combined with Topiroxostat.Approved, Illicit
QuinidineThe metabolism of Quinidine can be decreased when combined with Topiroxostat.Approved
QuinineThe metabolism of Quinine can be decreased when combined with Topiroxostat.Approved
RepaglinideThe metabolism of Repaglinide can be decreased when combined with Topiroxostat.Approved, Investigational
RifampicinThe metabolism of Rifampicin can be decreased when combined with Topiroxostat.Approved
RiociguatThe metabolism of Riociguat can be decreased when combined with Topiroxostat.Approved
RofecoxibThe metabolism of Rofecoxib can be decreased when combined with Topiroxostat.Investigational, Withdrawn
RosiglitazoneThe metabolism of Rosiglitazone can be decreased when combined with Topiroxostat.Approved, Investigational
RosuvastatinThe metabolism of Rosuvastatin can be decreased when combined with Topiroxostat.Approved
RupatadineThe metabolism of Rupatadine can be decreased when combined with Topiroxostat.Approved
Salicylic acidThe metabolism of Salicylic acid can be decreased when combined with Topiroxostat.Approved, Vet Approved
SelegilineThe metabolism of Selegiline can be decreased when combined with Topiroxostat.Approved, Investigational, Vet Approved
SelexipagThe metabolism of Selexipag can be decreased when combined with Topiroxostat.Approved
SeratrodastThe metabolism of Seratrodast can be decreased when combined with Topiroxostat.Approved
SertralineThe metabolism of Sertraline can be decreased when combined with Topiroxostat.Approved
SildenafilThe metabolism of Sildenafil can be decreased when combined with Topiroxostat.Approved, Investigational
SimvastatinThe metabolism of Simvastatin can be decreased when combined with Topiroxostat.Approved
SitagliptinThe metabolism of Sitagliptin can be decreased when combined with Topiroxostat.Approved, Investigational
SitaxentanThe metabolism of Sitaxentan can be decreased when combined with Topiroxostat.Approved, Investigational, Withdrawn
SorafenibThe metabolism of Sorafenib can be decreased when combined with Topiroxostat.Approved, Investigational
SulfadiazineThe metabolism of Sulfadiazine can be decreased when combined with Topiroxostat.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Sulfamethoxazole can be decreased when combined with Topiroxostat.Approved
SulfamoxoleThe metabolism of Sulfamoxole can be decreased when combined with Topiroxostat.Approved
SulfinpyrazoneThe metabolism of Sulfinpyrazone can be decreased when combined with Topiroxostat.Approved
SulfisoxazoleThe metabolism of Sulfisoxazole can be decreased when combined with Topiroxostat.Approved, Vet Approved
SuprofenThe metabolism of Suprofen can be decreased when combined with Topiroxostat.Approved, Withdrawn
TamoxifenThe metabolism of Tamoxifen can be decreased when combined with Topiroxostat.Approved
TapentadolThe metabolism of Tapentadol can be decreased when combined with Topiroxostat.Approved
TazaroteneThe metabolism of Tazarotene can be decreased when combined with Topiroxostat.Approved, Investigational
TemazepamThe metabolism of Temazepam can be decreased when combined with Topiroxostat.Approved
TenoxicamThe metabolism of Tenoxicam can be decreased when combined with Topiroxostat.Approved
TerbinafineThe metabolism of Terbinafine can be decreased when combined with Topiroxostat.Approved, Investigational, Vet Approved
TerfenadineThe metabolism of Terfenadine can be decreased when combined with Topiroxostat.Withdrawn
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Topiroxostat.Experimental
TestosteroneThe metabolism of Testosterone can be decreased when combined with Topiroxostat.Approved, Investigational
ThalidomideThe metabolism of Thalidomide can be decreased when combined with Topiroxostat.Approved, Investigational, Withdrawn
TheophyllineThe metabolism of Theophylline can be decreased when combined with Topiroxostat.Approved
ThiamylalThe metabolism of Thiamylal can be decreased when combined with Topiroxostat.Approved, Vet Approved
TolbutamideThe metabolism of Tolbutamide can be decreased when combined with Topiroxostat.Approved
TolterodineThe metabolism of Tolterodine can be decreased when combined with Topiroxostat.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Topiroxostat.Approved, Investigational
TorasemideThe metabolism of Torasemide can be decreased when combined with Topiroxostat.Approved
TrabectedinThe metabolism of Trabectedin can be decreased when combined with Topiroxostat.Approved, Investigational
TreprostinilThe metabolism of Treprostinil can be decreased when combined with Topiroxostat.Approved, Investigational
TretinoinThe metabolism of Tretinoin can be decreased when combined with Topiroxostat.Approved, Investigational, Nutraceutical
TrimethadioneThe metabolism of Trimethadione can be decreased when combined with Topiroxostat.Approved
TrimethoprimThe metabolism of Trimethoprim can be decreased when combined with Topiroxostat.Approved, Vet Approved
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Topiroxostat.Approved
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Topiroxostat.Investigational, Withdrawn
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Topiroxostat.Approved, Investigational, Nutraceutical
ValdecoxibThe metabolism of Valdecoxib can be decreased when combined with Topiroxostat.Investigational, Withdrawn
Valproic AcidThe metabolism of Valproic Acid can be decreased when combined with Topiroxostat.Approved, Investigational
ValsartanThe metabolism of Valsartan can be decreased when combined with Topiroxostat.Approved, Investigational
VelpatasvirThe metabolism of Velpatasvir can be decreased when combined with Topiroxostat.Approved
VenlafaxineThe metabolism of Venlafaxine can be decreased when combined with Topiroxostat.Approved
VerapamilThe metabolism of Verapamil can be decreased when combined with Topiroxostat.Approved
VicrivirocThe metabolism of Vicriviroc can be decreased when combined with Topiroxostat.Investigational
VismodegibThe metabolism of Vismodegib can be decreased when combined with Topiroxostat.Approved
VoriconazoleThe metabolism of Voriconazole can be decreased when combined with Topiroxostat.Approved, Investigational
VortioxetineThe metabolism of Vortioxetine can be decreased when combined with Topiroxostat.Approved
VoxilaprevirThe metabolism of Voxilaprevir can be decreased when combined with Topiroxostat.Approved
WarfarinThe metabolism of Warfarin can be decreased when combined with Topiroxostat.Approved
XimelagatranThe metabolism of Ximelagatran can be decreased when combined with Topiroxostat.Approved, Investigational, Withdrawn
ZafirlukastThe metabolism of Zafirlukast can be decreased when combined with Topiroxostat.Approved, Investigational
ZalcitabineThe metabolism of Zalcitabine can be decreased when combined with Topiroxostat.Approved, Investigational
ZaltoprofenThe metabolism of Zaltoprofen can be decreased when combined with Topiroxostat.Approved, Investigational
ZidovudineThe metabolism of Zidovudine can be decreased when combined with Topiroxostat.Approved
ZileutonThe metabolism of Zileuton can be decreased when combined with Topiroxostat.Approved, Investigational, Withdrawn
ZolpidemThe metabolism of Zolpidem can be decreased when combined with Topiroxostat.Approved
ZopicloneThe metabolism of Zopiclone can be decreased when combined with Topiroxostat.Approved
Food Interactions
Not Available

References

General References
  1. Matsumoto K, Okamoto K, Ashizawa N, Nishino T: FYX-051: a novel and potent hybrid-type inhibitor of xanthine oxidoreductase. J Pharmacol Exp Ther. 2011 Jan;336(1):95-103. doi: 10.1124/jpet.110.174540. Epub 2010 Oct 15. [PubMed:20952484]
  2. Hosoya T, Ohno I, Nomura S, Hisatome I, Uchida S, Fujimori S, Yamamoto T, Hara S: Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout. Clin Exp Nephrol. 2014 Dec;18(6):876-84. doi: 10.1007/s10157-014-0935-8. Epub 2014 Jan 22. [PubMed:24448692]
  3. Nishino T, Okamoto K: Mechanistic insights into xanthine oxidoreductase from development studies of candidate drugs to treat hyperuricemia and gout. J Biol Inorg Chem. 2015 Mar;20(2):195-207. doi: 10.1007/s00775-014-1210-x. Epub 2014 Dec 12. [PubMed:25501928]
  4. Sugiyama A, Hashimoto H, Nakamura Y, Fujita T, Kumagai Y: QT/QTc study conducted in Japanese adult healthy subjects: a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation. J Clin Pharmacol. 2014 Apr;54(4):446-52. doi: 10.1002/jcph.226. Epub 2013 Nov 22. [PubMed:24214189]
  5. Okamoto K, Eger BT, Nishino T, Kondo S, Pai EF, Nishino T: An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition. J Biol Chem. 2003 Jan 17;278(3):1848-55. Epub 2002 Nov 5. [PubMed:12421831]
  6. Okamoto K, Matsumoto K, Hille R, Eger BT, Pai EF, Nishino T: The crystal structure of xanthine oxidoreductase during catalysis: implications for reaction mechanism and enzyme inhibition. Proc Natl Acad Sci U S A. 2004 May 25;101(21):7931-6. Epub 2004 May 17. [PubMed:15148401]
  7. Nakazawa T, Miyata K, Omura K, Iwanaga T, Nagata O: Metabolic profile of FYX-051 (4-(5-pyridin-4-yl-1h-[1,2,4]triazol-3-yl)pyridine-2-carbonitrile) in the rat, dog, monkey, and human: identification of N-glucuronides and N-glucosides. Drug Metab Dispos. 2006 Nov;34(11):1880-6. Epub 2006 Aug 16. [PubMed:16914512]
  8. Omura K, Nakazawa T, Sato T, Iwanaga T, Nagata O: Characterization of N-glucuronidation of 4-(5-pyridin-4-yl-1H-[1,2,4]triazol-3-yl) pyridine-2-carbonitrile (FYX-051): a new xanthine oxidoreductase inhibitor. Drug Metab Dispos. 2007 Dec;35(12):2143-8. Epub 2007 Aug 30. [PubMed:17761779]
  9. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]
External Links
PubChem Compound
5288320
PubChem Substance
46508374
ChemSpider
4450517
BindingDB
50311275
ChEMBL
CHEMBL1078685
HET
FYX
Wikipedia
Topiroxostat
PDB Entries
1v97
MSDS
Download (23.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingBasic ScienceHyperuricemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0779 mg/mLALOGPS
logP1.47ALOGPS
logP1.82ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)11.06ChemAxon
pKa (Strongest Basic)3.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area91.14 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity90.47 m3·mol-1ChemAxon
Polarizability25.39 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9553
Caco-2 permeable+0.5089
P-glycoprotein substrateNon-substrate0.8142
P-glycoprotein inhibitor INon-inhibitor0.914
P-glycoprotein inhibitor IINon-inhibitor0.9566
Renal organic cation transporterNon-inhibitor0.743
CYP450 2C9 substrateNon-substrate0.8646
CYP450 2D6 substrateNon-substrate0.8876
CYP450 3A4 substrateNon-substrate0.7258
CYP450 1A2 substrateInhibitor0.84
CYP450 2C9 inhibitorNon-inhibitor0.8298
CYP450 2D6 inhibitorNon-inhibitor0.9604
CYP450 2C19 inhibitorNon-inhibitor0.7387
CYP450 3A4 inhibitorInhibitor0.5479
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6341
Ames testAMES toxic0.6839
CarcinogenicityNon-carcinogens0.8822
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8791 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9411
hERG inhibition (predictor II)Non-inhibitor0.9281
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyridyl-1,2,4-triazoles. These are organic compounds containing a pyridine ring attached to a 1,2,4-triazole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Pyridyltriazoles
Direct Parent
Pyridyl-1,2,4-triazoles
Alternative Parents
Triazoles / Heteroaromatic compounds / Nitriles / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Pyridyl-1,2,4-triazole / Heteroaromatic compound / 1,2,4-triazole / Triazole / Azole / Azacycle / Nitrile / Carbonitrile / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Omura K, Nakazawa T, Sato T, Iwanaga T, Nagata O: Characterization of N-glucuronidation of 4-(5-pyridin-4-yl-1H-[1,2,4]triazol-3-yl) pyridine-2-carbonitrile (FYX-051): a new xanthine oxidoreductase inhibitor. Drug Metab Dispos. 2007 Dec;35(12):2143-8. Epub 2007 Aug 30. [PubMed:17761779]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Miyata H, Takada T, Toyoda Y, Matsuo H, Ichida K, Suzuki H: Identification of Febuxostat as a New Strong ABCG2 Inhibitor: Potential Applications and Risks in Clinical Situations. Front Pharmacol. 2016 Dec 27;7:518. doi: 10.3389/fphar.2016.00518. eCollection 2016. [PubMed:28082903]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review [Link]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 14:47