Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP301JW)

• DOT Name: Delta(24)-sterol reductase (DHCR24)
• Synonyms: EC 1.3.1.72; 24-dehydrocholesterol reductase; 3-beta-hydroxysterol Delta-24-reductase; Diminuto/dwarf1 homolog; Seladin-1
• Gene Name: DHCR24
• Related Disease: Desmosterolosis
• UniProt ID: DHC24_HUMAN
• EC Number: 1.3.1.72
• Pfam ID: PF01565
• Sequence:
  MEPAVSLAVCALLFLLWVRLKGLEFVLIHQRWVFVCLFLLPLSLIFDIYYYVRAWVVFKL
  SSAPRLHEQRVRDIQKQVREWKEQGSKTFMCTGRPGWLTVSLRVGKYKKTHKNIMINLMD
  ILEVDTKKQIVRVEPLVTMGQVTALLTSIGWTLPVLPELDDLTVGGLIMGTGIESSSHKY
  GLFQHICTAYELVLADGSFVRCTPSENSDLFYAVPWSCGTLGFLVAAEIRIIPAKKYVKL
  RFEPVRGLEAICAKFTHESQRQENHFVEGLLYSLDEAVIMTGVMTDEAEPSKLNSIGNYY
  KPWFFKHVENYLKTNREGLEYIPLRHYYHRHTRSIFWELQDIIPFGNNPIFRYLFGWMVP
  PKISLLKLTQGETLRKLYEQHHVVQDMLVPMKCLQQALHTFQNDIHVYPIWLCPFILPSQ
  PGLVHPKGNEAELYIDIGAYGEPRVKHFEARSCMRQLEKFVRSVHGFQMLYADCYMNREE
  FWEMFDGSLYHKLREKLGCQDAFPEVYDKICKAARH
• Function: Catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis. In addition to its cholesterol-synthesizing activity, can protect cells from oxidative stress by reducing caspase 3 activity during apoptosis induced by oxidative stress. Also protects against amyloid-beta peptide-induced apoptosis.
• Tissue Specificity: Highly expressed in brain and adrenal gland with moderate expression in liver, lung, spleen, prostate and spinal cord. Low expression in heart, uterus and prostate. Undetectable in blood cells. In the brain, strongly expressed in cortical regions, substantia nigra, caudate nucleus, hippocampus, medulla oblongata and pons. In brains affected by Alzheimer disease, expression in the inferior temporal lobe is substantially lower than in the frontal cortex.
• KEGG Pathway:
  Steroid biosynthesis (hsa00100)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Cholesterol biosynthesis via desmosterol (R-HSA-6807047)
  Cholesterol biosynthesis via lathosterol (R-HSA-6807062)
  Cholesterol biosynthesis (R-HSA-191273)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Desmosterolosis	DIS9XV8L	Definitive	Autosomal recessive	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Delta(24)-sterol reductase (DHCR24) affects the response to substance of Paclitaxel.	[35]

35 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 Delta(24)-sterol reductase (DHCR24).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Delta(24)-sterol reductase (DHCR24).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Delta(24)-sterol reductase (DHCR24).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Delta(24)-sterol reductase (DHCR24).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Delta(24)-sterol reductase (DHCR24).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Delta(24)-sterol reductase (DHCR24).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Delta(24)-sterol reductase (DHCR24).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Delta(24)-sterol reductase (DHCR24).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Delta(24)-sterol reductase (DHCR24).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Delta(24)-sterol reductase (DHCR24).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Delta(24)-sterol reductase (DHCR24).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Delta(24)-sterol reductase (DHCR24).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Delta(24)-sterol reductase (DHCR24).	[14]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Delta(24)-sterol reductase (DHCR24).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Delta(24)-sterol reductase (DHCR24).	[16]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Delta(24)-sterol reductase (DHCR24).	[17]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Delta(24)-sterol reductase (DHCR24).	[18]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Delta(24)-sterol reductase (DHCR24).	[19]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Delta(24)-sterol reductase (DHCR24).	[17]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Delta(24)-sterol reductase (DHCR24).	[20]
Prasterone	DM67VKL	Approved	Prasterone affects the expression of Delta(24)-sterol reductase (DHCR24).	[21]
Dutasteride	DMQ4TJK	Approved	Dutasteride decreases the expression of Delta(24)-sterol reductase (DHCR24).	[22]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Delta(24)-sterol reductase (DHCR24).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Delta(24)-sterol reductase (DHCR24).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Delta(24)-sterol reductase (DHCR24).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Delta(24)-sterol reductase (DHCR24).	[26]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Delta(24)-sterol reductase (DHCR24).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Delta(24)-sterol reductase (DHCR24).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Delta(24)-sterol reductase (DHCR24).	[29]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Delta(24)-sterol reductase (DHCR24).	[30]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Delta(24)-sterol reductase (DHCR24).	[31]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Delta(24)-sterol reductase (DHCR24).	[32]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Delta(24)-sterol reductase (DHCR24).	[33]
propylpyrazoletriol	DMTCP8K	Investigative	propylpyrazoletriol increases the expression of Delta(24)-sterol reductase (DHCR24).	[34]
diarylpropionitril	DM14X29	Investigative	diarylpropionitril increases the expression of Delta(24)-sterol reductase (DHCR24).	[34]

References

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