Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFC7K35)

• DOT Name: Vitamin D3 receptor
• Synonyms: VDR; 1,25-dihydroxyvitamin D3 receptor; Nuclear receptor subfamily 1 group I member 1
• Gene Name: VDR
• Related Disease:
  Vitamin D-dependent rickets, type 2A
  Vitamin D-dependent rickets, type 2
• UniProt ID: VDR_HUMAN
• PDB ID: 1DB1 ; 1IE8 ; 1IE9 ; 1KB2 ; 1KB4 ; 1KB6 ; 1S0Z ; 1S19 ; 1TXI ; 1YNW ; 2HAM ; 2HAR ; 2HAS ; 2HB7 ; 2HB8 ; 3A2I ; 3A2J ; 3A3Z ; 3A40 ; 3A78 ; 3AUQ ; 3AUR ; 3AX8 ; 3AZ1 ; 3AZ2 ; 3AZ3 ; 3B0T ; 3CS4 ; 3CS6 ; 3KPZ ; 3M7R ; 3OGT ; 3P8X ; 3TKC ; 3VHW ; 3W0A ; 3W0C ; 3W0Y ; 3WGP ; 3WWR ; 3X31 ; 3X36 ; 4G2I ; 4ITE ; 4ITF ; 5GT4 ; 5V39 ; 5YSY ; 5YT2 ; 7QPP
• Pfam ID: PF00104 ; PF00105
• Sequence:
  MEAMAASTSLPDPGDFDRNVPRICGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTC
  PFNGDCRITKDNRRHCQACRLKRCVDIGMMKEFILTDEEVQRKREMILKRKEEEALKDSL
  RPKLSEEQQRIIAILLDAHHKTYDPTYSDFCQFRPPVRVNDGGGSHPSRPNSRHTPSFSG
  DSSSSCSDHCITSSDMMDSSSFSNLDLSEEDSDDPSVTLELSQLSMLPHLADLVSYSIQK
  VIGFAKMIPGFRDLTSEDQIVLLKSSAIEVIMLRSNESFTMDDMSWTCGNQDYKYRVSDV
  TKAGHSLELIEPLIKFQVGLKKLNLHEEEHVLLMAICIVSPDRPGVQDAALIEAIQDRLS
  NTLQTYIRCRHPPPGSHLLYAKMIQKLADLRSLNEEHSKQYRCLSFQPECSMKLTPLVLE
  VFGNEIS
• Function: Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells. Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Plays a central role in calcium homeostasis. Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites.
• KEGG Pathway:
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
  Mineral absorption (hsa04978)
  Tuberculosis (hsa05152)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  Nuclear Receptor transcription pathway (R-HSA-383280)
  SUMOylation of intracellular receptors (R-HSA-4090294)
  Vitamin D (calciferol) metabolism (R-HSA-196791)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Vitamin D-dependent rickets, type 2A	DISL11VX	Definitive	Autosomal recessive	[1]
Vitamin D-dependent rickets, type 2	DISZHFC3	Supportive	Autosomal recessive	[2]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cytarabine	DMZD5QR	Approved	Vitamin D3 receptor affects the response to substance of Cytarabine.	[38]
Aspirin	DM672AH	Approved	Vitamin D3 receptor affects the response to substance of Aspirin.	[39]
Warfarin	DMJYCVW	Approved	Vitamin D3 receptor affects the response to substance of Warfarin.	[41]
Mercaptopurine	DMTM2IK	Approved	Vitamin D3 receptor affects the response to substance of Mercaptopurine.	[38]
Alendronate	DMY2KX9	Approved	Vitamin D3 receptor affects the response to substance of Alendronate.	[42]

This DOT Affected the Regulation of Drug Effects of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dopamine	DMPGUCF	Approved	Vitamin D3 receptor increases the abundance of Dopamine.	[40]
Norepinephrine	DMOUC09	Approved	Vitamin D3 receptor increases the abundance of Norepinephrine.	[40]
ANW-32821	DMMJOZD	Phase 2	Vitamin D3 receptor affects the abundance of ANW-32821.	[43]
Homovanillic acid	DM0SHPY	Investigative	Vitamin D3 receptor increases the abundance of Homovanillic acid.	[40]

2 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 Vitamin D3 receptor.	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Vitamin D3 receptor.	[30]

40 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 Vitamin D3 receptor.	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Vitamin D3 receptor.	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Vitamin D3 receptor.	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Vitamin D3 receptor.	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Vitamin D3 receptor.	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Vitamin D3 receptor.	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Vitamin D3 receptor.	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the activity of Vitamin D3 receptor.	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Vitamin D3 receptor.	[12]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Vitamin D3 receptor.	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Vitamin D3 receptor.	[13]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Vitamin D3 receptor.	[14]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the activity of Vitamin D3 receptor.	[16]
Chenodiol	DMQ8JIK	Approved	Chenodiol increases the expression of Vitamin D3 receptor.	[13]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid increases the expression of Vitamin D3 receptor.	[17]
Estriol	DMOEM2I	Approved	Estriol increases the expression of Vitamin D3 receptor.	[18]
Methoxsalen	DME8FZ9	Approved	Methoxsalen increases the expression of Vitamin D3 receptor.	[19]
Promegestone	DMK4S8I	Approved	Promegestone increases the expression of Vitamin D3 receptor.	[20]
Prednisone	DM2HG4X	Approved	Prednisone increases the expression of Vitamin D3 receptor.	[20]
Idarubicin	DMM0XGL	Approved	Idarubicin decreases the activity of Vitamin D3 receptor.	[16]
Alfacalcidol	DM1237M	Phase 4	Alfacalcidol increases the activity of Vitamin D3 receptor.	[23]
Lacidipine	DMQP5I3	Phase 4	Lacidipine increases the activity of Vitamin D3 receptor.	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Vitamin D3 receptor.	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Vitamin D3 receptor.	[25]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Vitamin D3 receptor.	[26]
Manidipine	DMJPGUA	Phase 3	Manidipine increases the activity of Vitamin D3 receptor.	[16]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Vitamin D3 receptor.	[25]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Vitamin D3 receptor.	[28]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Vitamin D3 receptor.	[29]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Vitamin D3 receptor.	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Vitamin D3 receptor.	[31]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Vitamin D3 receptor.	[28]
GW-501516	DMPL2KM	Discontinued in Phase 4	GW-501516 increases the expression of Vitamin D3 receptor.	[17]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID increases the expression of Vitamin D3 receptor.	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Vitamin D3 receptor.	[33]
U0126	DM31OGF	Investigative	U0126 increases the expression of Vitamin D3 receptor.	[34]
Kaempferol	DMHEMUB	Investigative	Kaempferol increases the activity of Vitamin D3 receptor.	[11]
	DM9CEI5		increases the expression of Vitamin D3 receptor.	[13]
Alpha-linolenic acid	DMY64HE	Investigative	Alpha-linolenic acid increases the expression of Vitamin D3 receptor.	[17]
ISOPENTENYL PYROPHOSPHATE	DMTU05Y	Investigative	ISOPENTENYL PYROPHOSPHATE increases the expression of Vitamin D3 receptor.	[37]

7 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the degradation of Vitamin D3 receptor.	[15]
Cholic acid	DM7OKQV	Approved	Cholic acid increases the localization of Vitamin D3 receptor.	[21]
Paricalcitol	DMYBV3G	Approved	Paricalcitol affects the binding of Vitamin D3 receptor.	[22]
ED-71	DMRLXAI	Phase 3	ED-71 affects the binding of Vitamin D3 receptor.	[27]
Lexacalcitol	DMJ3ZT8	Discontinued in Phase 2	Lexacalcitol affects the binding of Vitamin D3 receptor.	[32]
Staurosporine	DM0E9BR	Investigative	Staurosporine increases the cleavage of Vitamin D3 receptor.	[35]
M-Phenoxybenzoic Acid For Cis-Isomer	DMJRK47	Investigative	M-Phenoxybenzoic Acid For Cis-Isomer affects the binding of Vitamin D3 receptor.	[36]

References

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