Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTHCPF)

• DTT Name: Cholesterol 24-monooxygenase (CYP46A1)
• Synonyms: Cytochrome P450 46A1; Cholesterol 24S-hydroxylase; CYP46; CH24H
• Gene Name: CYP46A1
• DTT Type: Discontinued target; [1]
• UniProt ID: CP46A_HUMAN
• TTD ID: T64242
• EC Number: EC 1.14.14.25
• Sequence:
  MSPGLLLLGSAVLLAFGLCCTFVHRARSRYEHIPGPPRPSFLLGHLPCFWKKDEVGGRVL
  QDVFLDWAKKYGPVVRVNVFHKTSVIVTSPESVKKFLMSTKYNKDSKMYRALQTVFGERL
  FGQGLVSECNYERWHKQRRVIDLAFSRSSLVSLMETFNEKAEQLVEILEAKADGQTPVSM
  QDMLTYTAMDILAKAAFGMETSMLLGAQKPLSQAVKLMLEGITASRNTLAKFLPGKRKQL
  REVRESIRFLRQVGRDWVQRRREALKRGEEVPADILTQILKAEEGAQDDEGLLDNFVTFF
  IAGHETSANHLAFTVMELSRQPEIVARLQAEVDEVIGSKRYLDFEDLGRLQYLSQVLKES
  LRLYPPAWGTFRLLEEETLIDGVRVPGNTPLLFSTYVMGRMDTYFEDPLTFNPDRFGPGA
  PKPRFTYFPFSLGHRSCIGQQFAQMEVKVVMAKLLQRLEFRLVPGQRFGLQEQATLKPLD
  PVLCTLRPRGWQPAPPPPPC
• 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. 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. 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. May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole.
• KEGG Pathway: Primary bile acid biosynthesis (hsa00120)
• Reactome Pathway:
  Endogenous sterols (R-HSA-211976)
  Synthesis of bile acids and bile salts via 24-hydroxycholesterol (R-HSA-193775)

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RC-8800	DMR6QMJ	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[1]

References

• [1] Clinical pipeline report, company report or official report of Boston Millennia Partners.