U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Approval Year

Substance Class Protein
Created
by admin
on Thu Jul 06 11:42:27 UTC 2023
Edited
by admin
on Thu Jul 06 11:42:27 UTC 2023
Protein Type ENZYME
Protein Sub Type CYTOCHROME P450
Sequence Origin HUMAN
Sequence Type COMPLETE
Record UNII
PUO0521HZV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CYTOCHROME P450 3A4
Common Name English
ALBENDAZOLE MONOOXYGENASE
Common Name English
CHOLESTEROL 25-HYDROXYLASE
Common Name English
CYP3A4
Common Name English
CYTOCHROME P 450 3A4
Common Name English
HUMAN CYTOCHROME P450 3A4
Common Name English
NIFEDIPINE OXIDASE
Common Name English
Code System Code Type Description
CAS
329736-03-0
Created by admin on Thu Jul 06 11:42:58 UTC 2023 , Edited by admin on Thu Jul 06 11:42:58 UTC 2023
PRIMARY
FDA UNII
PUO0521HZV
Created by admin on Thu Jul 06 11:42:58 UTC 2023 , Edited by admin on Thu Jul 06 11:42:58 UTC 2023
PRIMARY
EVMPD
SUB182775
Created by admin on Thu Jul 06 11:42:58 UTC 2023 , Edited by admin on Thu Jul 06 11:42:58 UTC 2023
PRIMARY
EC (ENZYME CLASS)
EC 1.14.13.67
Created by admin on Thu Jul 06 11:42:58 UTC 2023 , Edited by admin on Thu Jul 06 11:42:58 UTC 2023
PRIMARY
UNIPROT
P08684
Created by admin on Thu Jul 06 11:42:58 UTC 2023 , Edited by admin on Thu Jul 06 11:42:58 UTC 2023
PRIMARY
Related Record Type Details
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
Midazolam is the substrate.
INHIBITOR -> METABOLIC ENZYME
Measured by midazolam 1′-hydroxylation; 42% inhibition at 10 micromolar.
IC50
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> TARGET
PHARMAKINETIC ENHANCER
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
WEAK
TIME-DEPENDENT INHIBITION
Ki
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
COADMINSTERED WITH RITONAVIR TO INCREASE BIOAVAILABILITY
SUBSTRATE -> METABOLIC ENZYME
Tenapanor is a substrate of CYP3A4 and CYP3A5; however, none of the CYP enzymes was found to be responsible for ≥25% of its overall elimination.
SUBSTRATE -> METABOLIC ENZYME
NON-INHIBITOR -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
IN VITRO
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
IRREVERSIBLE INHIBITOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
In vivo, the sum of enzalutamide and M2 exposure was increased by 2.2-fold and 1.3-fold when it was co-administered with gemfibrozil (strong CYP2C8 inhibitor) or itraconazole (strong CYP3A4 inhibitor), respectively.
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
NON-SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
Drugs that induce or inhibit CYP3A, P-gp, and BCRP may affect temsavir plasma concentrations.
SUBSTRATE -> METABOLIC ENZYME
MAJOR
NON-INHIBITOR -> METABOLIC ENZYME
DID NOT INHIBIT ANY OTHER CYP ENZYMES
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
Unit K inact(min-1)
IRREVERSIBLE INHIBITOR
k(inactivation)
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
The following dose modifications are recommended: Strong CYP3A inhibitors: Reduce dose to 250 mg QD
NON-SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INDUCER -> METABOLIC ENZYME
The induction of CYP3A4 enzyme (3.9 times) was lower than the mRNA increase (65 times), indicating possible time-dependent inhibition.
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
Strong CYP3A inhibitor: co-administration of itraconazole, a strong CYP3A and P-gp inhibitor, increased gilteritinib systemic exposure by approximately 2.2- fold. Moderate CYP3A inhibitor: coadministration of fluconazole, a moderate CYP3A inhibitor, increased gilteritinib systemic exposure by approximately 1.4-fold.
IC50
INHIBITOR -> METABOLIC ENZYME
In an in-vitro study, eluxadoline appears to show time-dependent inhibition of CYP3A4 at 50 μM, a concentration that can be achieved in the gut (Igut is estimated to be 700 μM).
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
POTENT
INHIBITOR -> METABOLIC ENZYME
Lomitapide is a weak in vivo CYP3A inhibitor.
WEAK
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
CYP3A4 in the total clearance of erdafitinib is estimated to be 20%.
SUBSTRATE -> METABOLIC ENZYME
Co-administration with rifampin (P-gp and strong CYP3A inducer) decreased the AUC and Cmax of relugolix by 55% and 23%, respectively.
MAJOR
NON-SUBSTRATE -> METABOLIC ENZYME
high stability to human CYP4503A4 (85% remaining)
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
The following dose modifications are recommended: Sensitive CYP3A substrates: Avoid concomitant use.
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
moderate and strong inducers of CYP3A4 should not be co-administered due to the potential for loss of efficacy.
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
IN VITRO
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
sensitive substrates of CYP3A4 with a narrow therapeutic index should not be coadministered.
STRONG
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INDUCER -> METABOLIC ENZYME
Tafamidis induced CYP3A4 in vitro with an EC50 of 28 μM.
EC50
INHIBITOR -> METABOLIC ENZYME
Rifamycin is an inhibitor of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5 in vitro, however, based on systemic concentrations of rifamycin observed after administration of the recommended dose clinically relevant inhibition of these enzymes in vivo is unlikely.
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
POTENT
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
POTENT
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
Based on in vitro assessment, CYP3A4 (41.9%) was the predominant cytochrome P450 (CYP) isoform responsible for the metabolism of belumosudil.
MAJOR
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
RESPONSIBLE FOR 90 PERCENT OF METABOLISM
MAJOR
INHIBITOR -> METABOLIC ENZYME
Lonafarnib is a potent CYP3A time-dependent and mechanism-based inhibitor.
TIME-DEPENDENT INHIBITION
POTENCY
SUBSTRATE -> METABOLIC ENZYME
CYP3A4 showed no preference between the two enantiomers
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MINOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
Low systematic exposure
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
NON-SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
REVERSIBLE
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
6β-hydroxylation of testosterone
IC50
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
In vitro, ozenoxacin caused mild inhibition of CYP3A4 and CYP2C9 at high concentrations (≥100 μM).
INDUCER -> METABOLIC ENZYME
strong CYP3A4 induction in a concentration-dependent manner
MAY BE CLINICALLY SIGNIFICANT
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
NON-INHIBITOR -> METABOLIC ENZYME
NO INHIBITION AT 160 TIMES CMAX
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
NON-INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
in vitro studies utilizing human liver microsomes show that zafirlukast inhibits the cytochrome P450 CYP3A4 and CYP2C9 isoenzymes at concentrations close to the clinically achieved total plasma concentrations.
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> TARGET
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
WEAK INHIBITION
SUBSTRATE -> METABOLIC ENZYME
TISSUE EXPRESSION -> PARENT
INHIBITOR -> METABOLIC ENZYME
Coadministration of multiple doses of larotrectinib with a sensitive CYP3A4 substrate (midazolam) increased the AUCinf and Cmax of midazolam by 1.7-fold as compared to midazolam administered alone.
INHIBITOR -> METABOLIC ENZYME
Time-dependent inhibition. significant effect with other drugs which are substrate of CYP3A4 at clinical dose of Lenvatinib
MAJOR
PLASMA
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
COMPETITIVE INHIBITOR
Ki
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
Alosetron is metabolized by human microsomal cytochrome P450 (CYP), shown in vitro to involve enzymes 2C9 (30%), 3A4 (18%), and 1A2 (10%).
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
Coadministration of BIC (given without F/TAF) with rifampin decreased the mean BIC Cmax and AUC by 28% and 75%, respectively.
INHIBITOR -> METABOLIC ENZYME
SELECTIVE
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
TIME-DEPENDENT INHIBITION
INDUCER -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
Fidaxomicin and OP-1118 exhibited inhibitory potential for prominent intestinal CYP isoenzymes (CYP3A4, CYP2C9, and CYP2C19) in in vitro studies with human liver microsomes, based on estimated intestinal concentrations (fidaxomicin [I]2, 800 μg/mL).
IC50
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
IN-VITRO
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
In vitro, avapritinib is a time-dependent inhibitor as well as an inducer of CYP3A.
TIME-DEPENDENT INHIBITION
Ki
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
Zanubrutinib is a weak inducer of CYP3A4 and CYP2C19 in vivo.
WEAK
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
WEAK
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
NON-SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
Eribulin inhibited CYP3A4 activity with an apparent inhibition constant (Ki) value ranging from 3 μM to 30 μM (2190 ng/mL to 21,900 ng/mL), and the inhibition was demonstrated to be reversible and competitive.
Ki
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
In vitro and clinical studies indicate that ivacaftor is primarily metabolized by CYP3A.
MAJOR
ANIMAL ORTHOLOG->HUMAN ORTHOLOG
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
TIME-DEPENDENT INHIBITION
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
WEAK
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
WEAK
SUBSTRATE -> METABOLIC ENZYME
Does not induce CYP3A4 activity.
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
CYP 3A CONTRIBUTES FOR 42% OF IXAZOMIB METABOLISM
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MINOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
Moderate inhibitor
MINOR
INHIBITOR -> METABOLIC ENZYME
POTENT
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
TIME-DEPENDENT INHIBITION
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
REVERSIBLE
NON-INHIBITOR -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
Possible deadly drug interaction with CYP3A4 inhibitors
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MINOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
The fraction metabolized through CYP3A accounts for approximately 40% of the total hepatic panobinostat elimination.
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
NON-INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
IC50
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
In vitro, avapritinib is a time-dependent inhibitor as well as an inducer of CYP3A.
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
10% conversion to M1
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
APICAL
INHIBITOR -> METABOLIC ENZYME
Lapatinib is a mechanism-based inactivator of CYP3A4, most likely via the formation and further oxidation of its O-dealkylated metabolite to a quinoneimine that covalently modifies the CYP3A4 apoprotein and/or heme moiety.
TIME-DEPENDENT INHIBITION
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
MODERATE INDUCER THROUGH MEDIATED BY THE PREGNANE X RECEPTOR
SUBSTRATE -> METABOLIC ENZYME
the presence of strong CYP 3A4 inhibition by itraconazole can lead to an AUC increase of 400%.
MAJOR
INHIBITOR -> METABOLIC ENZYME
POTENT
INHIBITOR -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
Predicted no effect with other CYP2C8 substrates at clinical dose of Lenvatinib
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INDUCER -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
ANIMAL ORTHOLOG->HUMAN ORTHOLOG
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
MINOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
TIME-DEPENDENT INHIBITION
Ki
INHIBITOR -> METABOLIC ENZYME
COMPETITIVE INHIBITOR
Ki
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INDUCER -> METABOLIC ENZYME
The following dose modifications are recommended: Strong CYP3A inducers: Avoid concomitant use.
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MINOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
Lumacaftor is a strong inducers of CYP3A4
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MINOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
NON-INHIBITOR -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
Ki
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
REVERSIBLE
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
Linagliptin co-administration with P-gp and CYP 3A4 inducers may reduce its efficacy because of lower linagliptin exposures; therefore, it is strongly recommended to use the alternative treatments when it is to be co- administered with P-gp or CYP 3A4 inducers.
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
CYP3A4-mediated (oxidative) metabolism of canagliflozin is minimal (approximately 7%) in humans.
MINOR
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
metabolism by CYP3A4 (at least 29% of its overall metabolism); Ketoconazole(CYP 3A4 inhibition) increased sonidegib exposure 2.2-fold;Rifampin (CYP 3A4 induction) reduced exposure by 72%
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
E-Norendoxifen inhibited CYP3A4 3.7-fold more potently than Z-norendoxifen.
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
NON-SUBSTRATE -> METABOLIC ENZYME
NON-INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
Metabolized by CYP3A4 (0 to 70%), CYP2C19 (0‐20%), and FMO3 (0‐33%) in vitro.
SUBSTRATE -> METABOLIC ENZYME
NON-SUBSTRATE -> METABOLIC ENZYME
WAS NOT A SUBSTRATE FOR ANY OTHER CYP ENZYME
INDUCER -> METABOLIC ENZYME
Delafloxacin was a mild inducer (less than 2 fold) of CYP3A4 at a clinically relevant concentration.
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INDUCER -> METABOLIC ENZYME
Strong Inducer
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
Lapatinib is a mechanism-based inactivator of CYP3A4, most likely via the formation and further oxidation of its O-dealkylated metabolite to a quinoneimine that covalently modifies the CYP3A4 apoprotein and/or heme moiety
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
In human liver microsomes, dasatinib was a weak time-dependent inhibitor of CYP3A4.
TIME-DEPENDENT INHIBITION
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> TARGET
MINOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
IN VITRO
INDUCER -> METABOLIC ENZYME
Both ACT-064992 and ACT-132577 can induce CYP3A4 enzymes in vitro.
INHIBITOR -> METABOLIC ENZYME
IC50
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
E-Norendoxifen inhibited CYP3A4 3.7-fold more potently than Z-norendoxifen.
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
NON-INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided
STRONG
NON-INDUCER -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
Ki
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
MAJOR
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
IN VITRO
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
MODERATE
INHIBITOR -> METABOLIC ENZYME
MODERATE
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
NON-INHIBITOR -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INDUCER -> METABOLIC ENZYME
MINOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
In vitro, alpelisib is a strong time-dependent inhibitor of CYP3A4.
TIME-DEPENDENT INHIBITION
Ki
SUBSTRATE -> METABOLIC ENZYME
MINOR
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
Plasma concentration will significantly increase if taken with medications that are strong CYP3A4 inhibitors (i.e. erythromycin, ritonavir) and will significantly decrease if taken with strong CYP3A4 inducers (i.e. efavirenz, rifampin, Saint John's wort).
SUBSTRATE -> METABOLIC ENZYME
SUBSTRATE -> METABOLIC ENZYME
COMPETITIVE INHIBITOR
Ki
SUBSTRATE -> METABOLIC ENZYME
MAJOR
SUBSTRATE -> METABOLIC ENZYME
Metabolism of entrectinib is primary mediated by CYP3A4 (> 90%)
MAJOR
SUBSTRATE -> METABOLIC ENZYME
INHIBITOR -> METABOLIC ENZYME
WEAK
IC50