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Drug-Target Interaction

Drug

show drug details
PubChem ID:5505
Structure:
Synonyms:
1-butyl-3-(4-methylphenyl)sulfonylurea
1-Butyl-3-(4-methylphenylsulfonyl)urea
1-Butyl-3-(p-methylphenylsulfonyl)urea
1-Butyl-3-(p-tolylsulfonyl)urea
1-Butyl-3-(para-tolylsulfonyl) urea
1-Butyl-3-tosylurea
1-p-Toluenesulfonyl-3-butylurea
100735-34-0
3-(p-Tolyl-4-sulfonyl)-1-butylurea
3-(p-tolylsulfonyl)-1-butylurea
3-butyl-1-[(4-methylbenzene)sulfonyl]urea
3-[p-Tolyl-4-sulfonyl]-1-butylurea
4-11-00-00396 (Beilstein Handbook Reference)
46968_FLUKA
46968_RIEDEL
64-77-7
AB00052110
AB1004876
AC-12490
AC1L1KHP
AC1Q2X3T
Aglicid
AIDS-097016
AIDS097016
Apo-Tolbutamide
Apotex Brand of Tolbutamide
Arcosal
Arkozal
Artosin
Artozin
Aventis Brand of Tolbutamide
Beglucin
Benzenesulfonamide, N-((butylamino)carbonyl)-4-methyl-
Benzenesulfonamide, N-[(butylamino)carbonyl]-4-methyl-
Berlin Chemie Brand of Tolbutamide
Berlin-Chemie Brand of Tolbutamide
BIDD:PXR0179
BIM-0051121.0001
Bio1_000206
Bio1_000695
Bio1_001184
Bio2_000227
Bio2_000707
BPBio1_000131
BRD-K85119730-001-06-5
BRN 1984428
BSPBio_000119
BSPBio_001507
BSPBio_002078
Butamid
Butamide
Butamide Brand of Tolbutamide
Butamidum
BZ 55
C07148
C12H18N2O3S
CAS-64-77-7
CBiol_001920
CCG-39141
CCRIS 592
CHEBI:27999
CHEMBL782
cMAP_000008
CPD000058363
D 860
D00380
D014044
DB01124
Diaben
Diabesan
Diabetamid
Diabetol
Diabuton
Diasulfon
Diaval
Dirastan
DivK1c_000341
Dolipol
Drabet
EINECS 200-594-3
EU-0101154
Glyconon
HLS 831
HMS1361L09
HMS1568F21
HMS1791L09
HMS1989L09
HMS2089C17
HMS2092M21
HMS2095F21
HMS2232H16
HMS3259A08
HMS3263H09
HMS501B03
Hoechst Brand of Tolbutamide
HSDB 3393
IDI1_000341
IDI1_033977
Ipoglicone
KBio1_000341
KBio2_000227
KBio2_000927
KBio2_002275
KBio2_002795
KBio2_003495
KBio2_004843
KBio2_005363
KBio2_006063
KBio2_007411
KBio3_000453
KBio3_000454
KBio3_001578
KBio3_002755
KBioGR_000227
KBioGR_000795
KBioGR_002275
KBioSS_000227
KBioSS_000927
KBioSS_002276
Lopac-T-0891
Lopac0_001154
LS-278
MLS000028399
MLS001148399
MLS002152944
Mobenol
N-((butylamino) carbonyl)-4-methylbenzenesulfonamide
N-((Butylamino)carbonyl)-4-methylbenzenesulfonamide
N-(4-Methylbenzenesulfonyl)-N'-butylurea
N-(4-Methylphenylsulfonyl)-N'-butylurea
N-(p-Tolylsulfonyl)-N'-butylcarbamide
N-(p-tolylsulfonyl)-N'-n-butylurea
N-(Sulfonyl-p-methylbenzene)-N'-butylurea
N-(Sulfonyl-p-methylbenzene)-N'-N-butylurea
N-4-(Methylbenzolsulfonyl)-n-butylurea
N-4-Methylbenzolsulfonyl-N-butylurea
N-Butyl-N'-(4-methylphenylsulfonyl)urea
N-Butyl-N'-(p-tolylsulfonyl)urea
N-Butyl-N'-p-toluenesulfonylurea
N-Butyl-N'-toluene-p-sulfonylurea
N-n-Butyl-N'-tosylurea
N-[(butylamino)carbonyl]-4-methylbenzenesulfonamide
NCGC00015999-01
NCGC00015999-02
NCGC00015999-03
NCGC00015999-04
NCGC00015999-05
NCGC00015999-06
NCGC00015999-07
NCGC00015999-08
NCGC00015999-09
NCGC00015999-10
NCGC00015999-11
NCGC00015999-12
NCGC00015999-13
NCGC00015999-14
NCGC00015999-15
NCGC00015999-16
NCGC00015999-17
NCGC00022721-03
NCGC00022721-04
NCGC00022721-05
NCGC00022721-06
NCGC00022721-07
NCGC00022721-08
NCGC00022721-09
NCGC00022721-10
NCI-C01763
NCIOpen2_009592
NINDS_000341
Novo-Butamide
NSC 23813
NSC23813
Orabet
Oralin
Oramide
Orezan
Orinase
Orinase (TN)
Orinaz
Oterben
Pharmacia Brand of Tolbutamide
Pramidex
Prestwick0_000190
Prestwick1_000190
Prestwick2_000190
Prestwick3_000190
Prestwick_471
R.A.N. Brand of Tolbutamide
Rastinon
Restinon
SAM002554936
SK-Tolbutamide
SMR000058363
SPBio_001000
SPBio_002040
SPECTRUM1500581
Spectrum2_001210
Spectrum3_000599
Spectrum4_000358
Spectrum5_001272
Spectrum_000447
ST5409552
T 0891
T0891_FLUKA
T0891_SIGMA
Tarasina
TL8000121
Tol-Tab
Tolbet
Tolbusal
Tolbutamid
Tolbutamid R.A.N.
Tolbutamida
Tolbutamida [INN-Spanish]
Tolbutamide
Tolbutamide (JP15/USP/INN)
Tolbutamide (JP16/USP/INN)
Tolbutamide Aventis Brand
Tolbutamide Butamide Brand
Tolbutamide Hoechst Brand
TOLBUTAMIDE USP
Tolbutamide [BAN:INN:JAN]
Tolbutamide [INN:BAN:JAN]
Tolbutamidum
Tolbutamidum [INN-Latin]
Tolbutone
Toluina
Tolumid
toluran
Toluvan
Tolylsulfonylbutylurea
U 2043
UNII-982XCM1FOI
Urea, 1-butyl-3-(p-tolylsulfonyl)-
Valdecasas Brand of Tolbutamide
Willbutamide
WLN: 4MVMSWR D1
Yamanouchi Brand of Tolbutamide
ZINC01530703
ATC-Codes:
Side-Effects:
Side-EffectFrequency
thrombocytopenia0
leukopenia0
pancytopenia0
urticaria0
heartburn0
agranulocytosis0
porphyria0
hemolytic anemia0
pruritus0
aplastic anemia0
hypoglycemia0
hyponatremia0
photosensitivity0
porphyria cutanea tarda0
jaundice0
nausea0
siadh0
erythema0
headache0

Target

show target details
Uniprot ID:CP2C9_HUMAN
Synonyms:
(R)-limonene 6-monooxygenase
(S)-limonene 6-monooxygenase
(S)-limonene 7-monooxygenase
CYPIIC9
Cytochrome P450 2C9
P-450MP
P450 MP-4/MP-8
P450 PB-1
S-mephenytoin 4-hydroxylase
EC-Numbers:1.14.13.48
1.14.13.49
1.14.13.80
Organism:Homo sapiens
Human
PDB IDs:1OG2 1OG5 1R9O
Structure:
1R9O

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----
----
----
----
----
----
----
----
----
----
----
----
----
----
70000---

References:

016128907
10064574
1068138
10901704
11159803
1551116
1857342
7628308
8286335
Thiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid.. M P López-Garcia; P M Dansette; D Mansuy (1994) Biochemistry display abstract
Oxidation of tienilic acid (TA) by microsomes of yeast expressing two closely related human liver cytochrome P-450s (P450), P450 2C9 and 2C10, led to catalysis-dependent loss of activity of these P450s. Under identical conditions, oxidation of a tienilic acid isomer (TAI) failed to give any P450 inactivation. The loss of P450 activity during TA oxidation was concomitant with product (5-hydroxytienilic acid, 5-OHTA) formation, showed pseudo-first-order and saturation kinetics, and was inhibited by an alternative substrate, tolbutamide. Covalent binding of TA metabolites to microsomal proteins occurred in parallel with enzyme inactivation and was partially inhibited by the presence of glutathione in the reaction medium. However, glutathione did not protect P450 enzyme from inactivation. Thus, TA exhibited all of the characteristics of a mechanism-based inactivator for P450 2C9 and 2C10 enzymes. The following kinetic parameters were determined in the case of P450 2C10: t1/2,max = 3.4 min, k(inact) = 3.6 10(-3) s-1, KI = 4.3 microM, k(inact)/KI = 813 L mol-1 s-1, and partition ratio = 11.6. Moreover, a specific covalent binding of 0.9 mol of TA metabolite per mole of P450 2C10 was found to occur before the complete loss of enzyme activity (in incubations performed in the presence of glutathione). A plausible mechanism for P450 2C10 (2C9) inactivation during TA oxidation is proposed. It involves the intermediate formation of an electrophilic thiophene sulfoxide, which may react at position 5 of its thiophene ring either with H2O to give 5-OHTA or with a nucleophilic group of an amino acid residue of the P450 active site, which results in its covalent binding to P450 protein. This alkylation and inactivation of P450 2C9 (2C10) by TA could be a starting point for the appearance of anti-P450 2C antibodies detected in patients treated with TA and suffering from immunoallergic hepatitis.
9152599
Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase.. S W Grimm; M C Dyroff (1997) Drug metabolism and disposition: the biological fate of chemicals display abstract
Anastrozole (2,2'[5(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]- bis(2-methylproprionitrile)) is a potent third-generation inhibitor of aromatase, currently marketed as a treatment for postmenopausal women with advanced breast cancer. While its potency and selectivity for inhibition of estrogen synthesis has been established in both preclinical and clinical studies, this study used in vitro methods to examine the effects of anastrozole on several drug metabolizing CYP enzymes found in human liver. Human liver microsomes were co-incubated with anastrozole and probe substrates for CYP1A2 (phenacetin), CYP2A6 (coumarin), CYP2C9 (tolbutamide), CYP2D6 (dextromethorphan), and CYP3A (nifedipine). The formation of the CYP-specific metabolites following co-incubation with various anastrozole concentrations was determined to establish IC50 and Ki values for these enzymes. While anastrozole did not inhibit CYP2A6 and CYP2D6 activities at concentrations below 500 microM, this compound inhibited CYP1A2, CYP2C9, and CYP3A activities with Ki values of 8, 10, and 10 microM, respectively. Dixon plots used to determine the Ki values for the inhibition of CYP1A2 and CYP3A activities by anastrozole were biphasic, indicating additional lower affinity Ki values. Major metabolites of anastrozole did not retain the ability to inhibit the metabolism of nifedipine (CYP3A). The results of this study indicate that, although anastrozole can inhibit CYP1A2, 2C9, and 3A-mediated catalytic activities, this compound would not be expected to cause clinically significant interactions with other CYP-metabolized drugs at physiologically relevant concentrations achieved during therapy with Arimidex (Zeneca, Ltd., Macclesfield, UK) 1-mg.
9342584
9416970
9492390
9763401
9764927
Effects of propofol on human hepatic microsomal cytochrome P450 activities.. D McKillop; M J Wild; C J Butters; C Simcock (1998) Xenobiotica; the fate of foreign compounds in biological systems display abstract
1. The potential of propofol to inhibit the activity of major human cytochrome P450 enzymes has been examined in vitro using human liver microsomes. Propofol produced inhibition of CYP1A2 (phenacetin O-deethylation), CYP2C9 (tolbutamide 4'-hydroxylation), CYP2D6 (dextromethorphan O-demethylation) and CYP3A4 (testosterone 6beta-hydroxylation) activities with IC50 = 40, 49, 213 and 32 microM respectively. Ki for propofol against all of these enzymes with the exception of CYP2D6, where propofol showed little inhibitory activity, was 30, 30 and 19 microM respectively for CYPs 1A2, 2C9 and 3A4. 2. Furafylline, sulphaphenazole, quinidine and ketoconazole, known selective inhibitors of CYPs 1A2, 2C9, 2D6 and 3A4 respectively, were much more potent than propofol having IC50 = 0.8, 0.5, 0.2 and 0.1 microM; furafylline and sulphaphenazole yielded Ki = 0.6 and 0.7 microM respectively. 3. The therapeutic blood concentration of propofol (20 microM; 3-4 microg/ml) together with the in vitro Ki estimates for each of the major human P450 enzymes have been used to estimate the extent of cytochrome P450 inhibition, which may be produced in vivo by propofol. This in vitro-in vivo extrapolation indicates that the degree of inhibition of CYP1A2, 2C9 and 3A4 activity which could theoretically be produced in vivo by propofol is relatively low (40-51%); this is considered unlikely to have any pronounced clinical significance. 4. Although propofol has now been used in > 190 million people since its launch in 1986, there are only single reports of possible drug interactions between propofol and either alfentanil or warfarin. Consequently, it is difficult to conclude from either the published literature or the ZENECA safety database whether there is any evidence to indicate that propofol produces clinically significant drug interactions through inhibition of cytochrome P450-related drug metabolism.