Skip to content
PsychedeliaDokholyan Laboratory
TargetEnzymes

Cytochrome P450 3A4

Named enzymes, including the metabolising cytochromes and the monoamine oxidases.

Measurements
88
Compounds
30
Binding constants
10
Median pX
—

I · Identity

What this target is

Its function as UniProt states it, where in a cell the protein is found, and which cell types and tissues transcribe its gene.

Protein

CP3A4_HUMANCYP3A4Homo sapiens

Cytochrome P450 3A4

A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids10681376,11093772,11555828,12865317,14559847,15373842,15764715,19965576,20702771,21490593,21576599. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds12865317,14559847,15373842,15764715,21490593,21576599,2732228. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position11555828,12865317,14559847. Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone15373842,15764715,22773874,2732228. Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones15373842,15764715,2732228. Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis21576599. Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA)9435160. Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond19965576. Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling20702771. Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA)10681376. Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance11093772. Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol)11159812. Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole10759686. Hydroxylates antimalarial drug quinine8968357. Acts as a 1,4-cineole 2-exo-monooxygenase11695850. Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3))29461981

Quoted from UniProt’s FUNCTION annotation for P08684 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

PartnerCombinedExperimentDatabaseText mining
UGT2B70.9980.6260.9060.955
UGT1A10.9940.2940.9060.915
UGT1A60.9940.2940.9060.912
POR0.9920.2940.0000.900
UGT1A80.9920.0450.9060.914
UGT1A70.9920.0450.9060.914
UGT1A40.9920.0450.9060.915
UGT1A100.9920.0450.9060.914
CYP2E10.9910.0760.9090.863
CYP1A10.9870.0760.9090.810

Where it sits in the cell

  • Cytosol
  • Vesiclesadditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Endoplasmic reticulum membrane · Microsome membrane

Expression by cell type

Single cell type RNA, the 2 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

  • Hepatocytes3,988.6 nCPM
  • Enterocytes2,039.8 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

  • liver3,367.1 nTPM

II · Anatomy

Where the gene is transcribed

The same two atlases the compound plates use, asked about this gene alone. Brain on the left, peripheral and autonomic tissues on the right.

Brain

cerebral cortex — no resolved target expressed herecerebellum — 0.1 nTPM, from CYP3A4hippocampal formation — no resolved target expressed hereamygdala — no resolved target expressed herehypothalamus — no resolved target expressed herethalamus — no resolved target expressed herebasal ganglia — no resolved target expressed heremedulla oblongata — no resolved target expressed here

basal ganglia: drawn as the caudate nucleus, putamen and globus pallidus.

Measured but not drawn — this anatomogram has no outline for them: retina 0.3, pituitary gland 0.2.

Body

heart — 0.1 nTPM, from CYP3A4smooth muscle — no resolved target expressed herelung — no resolved target expressed hereliver — 3367.1 nTPM, from CYP3A4kidney — 4.2 nTPM, from CYP3A4stomach — 1.1 nTPM, from CYP3A4duodenum — 713.0 nTPM, from CYP3A4small intestine — 754.5 nTPM, from CYP3A4colon — 2.9 nTPM, from CYP3A4adrenal gland — 3.4 nTPM, from CYP3A4thyroid gland — no resolved target expressed herepancreas — 25.3 nTPM, from CYP3A4urinary bladder — no resolved target expressed hereskeletal muscle — 1.5 nTPM, from CYP3A4spleen — 0.1 nTPM, from CYP3A4salivary gland — 0.2 nTPM, from CYP3A4
03367 nTPM

Square-root ramp · shared scale across both plates

Shading is transcript level — not affinity, and not affinity combined with expression. Outlined but unshaded organs hold none of CYP3A4 transcript above the atlas’s detection threshold. Anatomy from EMBL-EBI Anatomogram (Apache License 2.0); regions identified by Uberon (uberon.org), CC BY 3.0.

Brain · 3

  • retina0.3 nTPM
  • pituitary gland0.2 nTPM
  • cerebellum0.1 nTPM

Peripheral and autonomic · 12

  • liver3367.1 nTPM
  • small intestine754.5 nTPM
  • duodenum713.0 nTPM
  • pancreas25.3 nTPM
  • kidney4.2 nTPM
  • adrenal gland3.4 nTPM
  • colon2.9 nTPM
  • skeletal muscle1.5 nTPM
  • stomach 11.1 nTPM
  • salivary gland0.2 nTPM
  • heart muscle0.1 nTPM
  • spleen0.1 nTPM

Transcript is not protein. These are RNA levels for CYP3A4, shaded on √nTPM so that a three-order range stays legible — on a linear ramp every region but the strongest would read as blank, which looks like absence rather than less. A region carrying no shading is one the atlas reports no consensus value for, not one where the gene is silent. And a gene being transcribed somewhere is not evidence that any compound reaches it. Human Protein Atlas, RNA expression, nTPM (normalized transcripts per million), consensus tissue dataset.

IV · Evidence

Every measurement at this target

Each row links to the ChEMBL assay it came from.

Equilibrium binding constants 10

Ki and Kd — a concentration at equilibrium. Directly comparable across rows at the same target.

TargetClassTypeValue (nM)pXOrganismAssay
Cytochrome P450 3A4EnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesKd— no normalized value— value does not convert to pXHomo sapiensCHEMBL5624355
Cytochrome P450 3A4EnzymesKd— no normalized value— value does not convert to pXHomo sapiensCHEMBL5624360
Cytochrome P450 3A4EnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL4687734
Cytochrome P450 3A4EnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138

Functional readouts 57

IC₅₀, EC₅₀, AC₅₀ and potency. Assay-dependent, and not interchangeable with a binding constant.

TargetClassTypeValue (nM)pXOrganismAssay
Cytochrome P450 3A4EnzymesIC502,9995.52Homo sapiensCHEMBL1063294
Cytochrome P450 3A4EnzymesPotency3,9815.40Homo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency10,0005.00Homo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency15,8494.80Homo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614108
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1741324
Cytochrome P450 3A4EnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1227231
Cytochrome P450 3A4EnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909138
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886
Cytochrome P450 3A4EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613886

Other measurements 21

Everything else ChEMBL recorded for this compound — percentage inhibition, efficacy, half-life, cytotoxicity. Reported in the assay's own units, which is why no value is converted here.

TargetClassTypeValue (nM)pXOrganismAssay
Cytochrome P450 3A4EnzymesFC— no normalized value— value does not convert to pXHomo sapiensCHEMBL4479000
Cytochrome P450 3A4EnzymesActivity— no normalized value— value does not convert to pXHomo sapiensCHEMBL1743273
Cytochrome P450 3A4EnzymesActivity— no normalized value— value does not convert to pXHomo sapiensCHEMBL1743273
Cytochrome P450 3A4EnzymesActivity— no normalized value— value does not convert to pXHomo sapiensCHEMBL1743273
Cytochrome P450 3A4EnzymesActivity— no normalized value— value does not convert to pXHomo sapiensCHEMBL1743273
Cytochrome P450 3A4EnzymesCL— no normalized value— value does not convert to pXHomo sapiensCHEMBL4707285
Cytochrome P450 3A4EnzymesFC— no normalized value— value does not convert to pXHomo sapiensCHEMBL4479051
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL5624330
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL5624335
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL5624340
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL5624347
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL5624352
Cytochrome P450 3A4EnzymesFC— no normalized value— value does not convert to pXHomo sapiensCHEMBL5624364
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL5624369
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL3538699
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL3538699
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL3538698
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL3538698
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL3538987
Cytochrome P450 3A4EnzymesDrug metabolism— no normalized value— value does not convert to pXHomo sapiensCHEMBL3538700
Cytochrome P450 3A4EnzymesInhibition— no normalized value— value does not convert to pXHomo sapiensCHEMBL954072
← All targets