Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKV62RZ)

• DOT Name: Methylsterol monooxygenase 1 (MSMO1)
• Synonyms: EC 1.14.18.9; C-4 methylsterol oxidase; Sterol-C4-methyl oxidase
• Gene Name: MSMO1
• Related Disease: Microcephaly-congenital cataract-psoriasiform dermatitis syndrome
• UniProt ID: MSMO1_HUMAN
• EC Number: 1.14.18.9
• Pfam ID: PF04116
• Sequence:
  MATNESVSIFSSASLAVEYVDSLLPENPLQEPFKNAWNYMLNNYTKFQIATWGSLIVHEA
  LYFLFCLPGFLFQFIPYMKKYKIQKDKPETWENQWKCFKVLLFNHFCIQLPLICGTYYFT
  EYFNIPYDWERMPRWYFLLARCFGCAVIEDTWHYFLHRLLHHKRIYKYIHKVHHEFQAPF
  GMEAEYAHPLETLILGTGFFIGIVLLCDHVILLWAWVTIRLLETIDVHSGYDIPLNPLNL
  IPFYAGSRHHDFHHMNFIGNYASTFTWWDRIFGTDSQYNAYNEKRKKFEKKTE
• Function: Catalyzes the three-step monooxygenation required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols, which can be subsequently metabolized to cholesterol. Also involved in drug metabolism, as it can metabolize eldecalcitol (ED-71 or 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)-cholecalciferol), a second-generation vitamin D analog, into 1alpha,2beta,25-trihydroxy vitamin D3; this reaction occurs via enzymatic hydroxylation and spontaneous O-dehydroxypropylation.
• KEGG Pathway:
  Steroid biosynthesis (hsa00100)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:HS00650-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microcephaly-congenital cataract-psoriasiform dermatitis syndrome	DISDMXLZ	Strong	Autosomal recessive	[1]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Methylsterol monooxygenase 1 (MSMO1) affects the response to substance of Paclitaxel.	[45]
Dasatinib	DMJV2EK	Approved	Methylsterol monooxygenase 1 (MSMO1) decreases the response to substance of Dasatinib.	[46]
Topotecan	DMP6G8T	Approved	Methylsterol monooxygenase 1 (MSMO1) affects the response to substance of Topotecan.	[45]
LY294002	DMY1AFS	Phase 1	Methylsterol monooxygenase 1 (MSMO1) decreases the response to substance of LY294002.	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Methylsterol monooxygenase 1 (MSMO1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Methylsterol monooxygenase 1 (MSMO1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[17]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[18]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[19]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[20]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[21]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[22]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[23]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[24]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[25]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[26]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[27]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[28]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[29]
Fenfluramine	DM0762O	Phase 3	Fenfluramine increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[30]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[31]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[34]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[35]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[36]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[38]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[39]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[40]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Methylsterol monooxygenase 1 (MSMO1).	[41]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[42]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[10]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[43]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Methylsterol monooxygenase 1 (MSMO1).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Methylsterol monooxygenase 1 (MSMO1).	[32]

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