General Information of the Protein
Protein ID
PT04604
Protein Name
Cholesterol 24-hydroxylase
Secondarily
Protein Name
Cholesterol 24-monooxygenase
Cholesterol 24S-hydroxylase
Cytochrome P450 46A1
Gene Name
CYP46A1
Secondarily
Gene Name
CYP46
Sequence
MSPGLLLLGSAVLLAFGLCCTFVHRARSRYEHIPGPPRPSFLLGHLPCFWKKDEVGGRVLQDVFLDWAKKYGPVVRVNVFHKTSVIVTSPESVKKFLMSTKYNKDSKMYRALQTVFGERLFGQGLVSECNYERWHKQRRVIDLAFSRSSLVSLMETFNEKAEQLVEILEAKADGQTPVSMQDMLTYTAMDILAKAAFGMETSMLLGAQKPLSQAVKLMLEGITASRNTLAKFLPGKRKQLREVRESIRFLRQVGRDWVQRRREALKRGEEVPADILTQILKAEEGAQDDEGLLDNFVTFFIAGHETSANHLAFTVMELSRQPEIVARLQAEVDEVIGSKRYLDFEDLGRLQYLSQVLKESLRLYPPAWGTFRLLEEETLIDGVRVPGNTPLLFSTYVMGRMDTYFEDPLTFNPDRFGPGAPKPRFTYFPFSLGHRSCIGQQFAQMEVKVVMAKLLQRLEFRLVPGQRFGLQEQATLKPLDPVLCTLRPRGWQPAPPPPPC
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Oxidoreductase
Function
P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain. Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholesterol diffusion out of neurons and its further degradation (PubMed:10377398, PubMed:14640697, PubMed:25017465, PubMed:18621681). By promoting constant cholesterol elimination in neurons, may activate the mevalonate pathway and coordinate the synthesis of new cholesterol and nonsterol isoprenoids involved in synaptic activity and learning (By similarity). Further hydroxylates cholesterol derivatives and hormone steroids on both the ring and side chain of these molecules, converting them into active oxysterols involved in lipid signaling and biosynthesis (PubMed:12077124, PubMed:14640697, PubMed:28190002). Acts as an epoxidase converting cholesta-5,24-dien-3beta-ol/desmosterol into (24S),25-epoxycholesterol, an abundant lipid ligand of nuclear NR1H2 and NR1H3 receptors shown to promote neurogenesis in developing brain (PubMed:25017465). May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole (PubMed:20667828).
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Uniprot ID
Primary ID:
Q9Y6A2

Secondarily ID:
B4DHP8
E7EQG9
Q8N2B0
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HGNC ID
HGNC:2641
Subcellular Location
Endoplasmic reticulum membrane
Microsome membrane
Postsynapse
Presynapse
Cell projection
Dendrite
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000131 , HEK293-F
Compound ID Compound Name Compound Formula
CP0569900
1-[4-(4-fluorophenyl)pyrimidin-5-yl]-N,N-dimethylpiperidine-4-carboxamide
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C18H21FN4O
 1
1
IC50 = 7.3 nM
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CP0568511
OV-935
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C23H23N3O2
 1
1
IC50 = 7.4 nM
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CP0539620
N-cyclopropyl-1-(4-phenylpyridin-3-yl)piperidine-4-carboxamide
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C20H23N3O
 1
1
IC50 = 8.1 nM
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CP0532742
N,N-dimethyl-1-[4-(4-methylpyrazol-1-yl)pyridin-3-yl]piperidine-4-carboxamide
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C17H23N5O
 1
1
IC50 = 8.5 nM
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CP0549071
1-[4-(4-bromopyrazol-1-yl)pyridin-3-yl]-N,N-dimethylpiperidine-4-carboxamide
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C16H20BrN5O
 1
1
IC50 = 9.5 nM
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CP0568512
1-[4-(4-cyclopropylpyrazol-1-yl)pyridin-3-yl]-N,N-dimethylpiperidine-4-carboxamide
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C19H25N5O
 1
1
IC50 = 12 nM
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CP0575871
N,N-dimethyl-1-[4-(5-methyl-1,3-thiazol-2-yl)pyridin-3-yl]piperidine-4-carboxamide
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C17H22N4OS
 1
1
IC50 = 12 nM
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CP0542627
N-ethyl-N-methyl-1-(4-phenylpyrimidin-5-yl)piperidine-4-carboxamide
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C19H24N4O
 1
1
IC50 = 14 nM
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CP0353597
N,N-dimethyl-1-(4-phenylpyrimidin-5-yl)piperidine-4-carboxamide
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C18H22N4O
 1
1
IC50 = 16 nM
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CP0344041
1-[4-(4-chloropyrazol-1-yl)pyridin-3-yl]-N,N-dimethylpiperidine-4-carboxamide
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C16H20ClN5O
 1
1
IC50 = 24 nM
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CP0542652
N-phenyl-1-(4-phenylpyrimidin-5-yl)piperidine-4-carboxamide
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C22H22N4O
 1
1
IC50 = 28 nM
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CP0538550
N-cyclopropyl-1-(4-phenylpyrimidin-5-yl)piperidine-4-carboxamide
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C19H22N4O
 1
1
IC50 = 44 nM
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CP0572085
N,N-dimethyl-1-(4-pyrazol-1-ylpyridin-3-yl)piperidine-4-carboxamide
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C16H21N5O
 1
1
IC50 = 48 nM
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CP0470902
N-cyclopropyl-4-(4-phenylpyridin-3-yl)piperazine-1-carboxamide
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C19H22N4O
 1
1
IC50 = 52 nM
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CP0567323
N-ethyl-1-(4-phenylpyrimidin-5-yl)piperidine-4-carboxamide
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C18H22N4O
 1
1
IC50 = 58 nM
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CP0569875
N,N-dimethyl-1-[4-[4-(trifluoromethyl)pyrazol-1-yl]pyridin-3-yl]piperidine-4-carboxamide
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C17H20F3N5O
 1
1
IC50 = 65 nM
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CP0575870
N,N-dimethyl-1-(4-pyridin-2-ylpyridin-3-yl)piperidine-4-carboxamide
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C18H22N4O
 1
1
IC50 = 68 nM
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CP0353596
N-methyl-1-(4-phenylpyrimidin-5-yl)piperidine-4-carboxamide
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C17H20N4O
 1
1
IC50 = 72 nM
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CP0534959
N-cyclopropyl-4-(4-phenylpyridin-3-yl)benzamide
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C21H18N2O
 1
1
IC50 = 74 nM
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CP0568510
N-cyclopropyl-1-(4-pyridin-2-ylpyridin-3-yl)piperidine-4-carboxamide
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C19H22N4O
 1
1
IC50 = 160 nM
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CP0044460
N-cyclohexyl-4-(1H-imidazol-5-yl)piperidine-1-carbothioamide
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C15H24N4S
 1
1
IC50 = 430 nM
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CP0572084
N-cyclopropyl-4-(4-phenylpyridin-3-yl)piperidine-1-carboxamide
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C20H23N3O
 1
1
IC50 = 950 nM
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CP0578752
N,N-dimethyl-1-[4-(3-methylpyrazol-1-yl)pyridin-3-yl]piperidine-4-carboxamide
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C17H23N5O
 1
1
IC50 = 1100 nM
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Clinical Information about the Protein
Target 1 ( Cholesterol 24-hydroxylase (CYP46A1) )
Target Type Clinical trial Target
Disease 1 Target-related Disease  1
1 Dravet syndrome [ICD-11: 8A61.11]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 TAK-935 Phase 2
Dravet syndrome
Target 2 ( Cholesterol 24-monooxygenase (CYP46A1) )
Target Type Discontinued Target