Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAYHG9C)

• DOT Name: Lanosterol 14-alpha demethylase (CYP51A1)
• Synonyms: LDM; EC 1.14.14.154; CYPLI; Cytochrome P450 51A1; CYP51A1; Cytochrome P450-14DM; Cytochrome P45014DM; Cytochrome P450LI; Sterol 14-alpha demethylase
• Gene Name: CYP51A1
• UniProt ID: CP51A_HUMAN
• PDB ID: 3JUS; 3JUV; 3LD6; 4UHI; 4UHL; 6Q2T; 6UEZ; 8SBI
• EC Number: 1.14.14.154
• Pfam ID: PF00067
• Sequence:
  MAAAAGMLLLGLLQAGGSVLGQAMEKVTGGNLLSMLLIACAFTLSLVYLIRLAAGHLVQL
  PAGVKSPPYIFSPIPFLGHAIAFGKSPIEFLENAYEKYGPVFSFTMVGKTFTYLLGSDAA
  ALLFNSKNEDLNAEDVYSRLTTPVFGKGVAYDVPNPVFLEQKKMLKSGLNIAHFKQHVSI
  IEKETKEYFESWGESGEKNVFEALSELIILTASHCLHGKEIRSQLNEKVAQLYADLDGGF
  SHAAWLLPGWLPLPSFRRRDRAHREIKDIFYKAIQKRRQSQEKIDDILQTLLDATYKDGR
  PLTDDEVAGMLIGLLLAGQHTSSTTSAWMGFFLARDKTLQKKCYLEQKTVCGENLPPLTY
  DQLKDLNLLDRCIKETLRLRPPIMIMMRMARTPQTVAGYTIPPGHQVCVSPTVNQRLKDS
  WVERLDFNPDRYLQDNPASGEKFAYVPFGAGRHRCIGENFAYVQIKTIWSTMLRLYEFDL
  IDGYFPTVNYTTMIHTPENPVIRYKRRSK
• Function: Sterol 14alpha-demethylase that plays a critical role in the cholesterol biosynthesis pathway, being cholesterol the major sterol component in mammalian membranes as well as a precursor for bile acid and steroid hormone synthesis. Cytochrome P450 monooxygenase that catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of sterols such as lanosterol (lanosta-8,24-dien-3beta-ol) and 24,25-dihydrolanosterol (DHL) in the form of formate, and converts the sterols to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol and 4,4-dimethyl-8,14-cholestadien-3beta-ol, respectively, which are intermediates of cholesterol biosynthesis. Can also demethylate substrates not intrinsic to mammals, such as eburicol (24-methylene-24,25-dihydrolanosterol), but at a lower rate than DHL.
• Tissue Specificity: Ubiquitously expressed with highest levels in testis, ovary, adrenal, prostate, liver, kidney and lung.
• KEGG Pathway:
  Steroid biosynthesis (hsa00100)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Endogenous sterols (R-HSA-211976)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665)
  Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:HS00076-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Lanosterol 14-alpha demethylase (CYP51A1) affects the response to substance of Fluorouracil.	[28]
Clotrimazole	DMMFCIH	Approved	Lanosterol 14-alpha demethylase (CYP51A1) decreases the response to substance of Clotrimazole.	[29]
Miconazole	DMPMYE8	Approved	Lanosterol 14-alpha demethylase (CYP51A1) decreases the response to substance of Miconazole.	[29]
Itraconazole	DMCR1MV	Approved	Lanosterol 14-alpha demethylase (CYP51A1) decreases the response to substance of Itraconazole.	[29]
Fluconazole	DMOWZ6B	Approved	Lanosterol 14-alpha demethylase (CYP51A1) decreases the response to substance of Fluconazole.	[29]
Voriconazole	DMAOL2S	Approved	Lanosterol 14-alpha demethylase (CYP51A1) decreases the response to substance of Voriconazole.	[29]
Econazole	DMFSWGH	Approved	Lanosterol 14-alpha demethylase (CYP51A1) decreases the response to substance of Econazole.	[29]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydrolanosterol	DMG0PXI	Investigative	Lanosterol 14-alpha demethylase (CYP51A1) decreases the abundance of Dihydrolanosterol.	[30]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Lanosterol 14-alpha demethylase (CYP51A1).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Lanosterol 14-alpha demethylase (CYP51A1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Lanosterol 14-alpha demethylase (CYP51A1).	[21]

28 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[13]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[15]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[17]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[18]
Letrozole	DMH07Y3	Approved	Letrozole decreases the activity of Lanosterol 14-alpha demethylase (CYP51A1).	[19]
FADROZOLE	DM3C5GZ	Approved	FADROZOLE decreases the activity of Lanosterol 14-alpha demethylase (CYP51A1).	[19]
Bifonazole	DM3KN7V	Approved	Bifonazole decreases the activity of Lanosterol 14-alpha demethylase (CYP51A1).	[19]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[20]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[25]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[7]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[10]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Lanosterol 14-alpha demethylase (CYP51A1).	[27]

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