Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZBTD8C)

• DOT Name: Very low-density lipoprotein receptor
• Synonyms: VLDL receptor; VLDL-R
• Gene Name: VLDLR
• Related Disease:
  Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1
  Cerebellar ataxia, intellectual disability, and dysequilibrium
• UniProt ID: VLDLR_HUMAN
• PDB ID: 1V9U; 3DPR; 6BYV; 8IHP
• Pfam ID: PF07645 ; PF14670 ; PF00057 ; PF00058
• Sequence:
  MGTSALWALWLLLALCWAPRESGATGTGRKAKCEPSQFQCTNGRCITLLWKCDGDEDCVD
  GSDEKNCVKKTCAESDFVCNNGQCVPSRWKCDGDPDCEDGSDESPEQCHMRTCRIHEISC
  GAHSTQCIPVSWRCDGENDCDSGEDEENCGNITCSPDEFTCSSGRCISRNFVCNGQDDCS
  DGSDELDCAPPTCGAHEFQCSTSSCIPISWVCDDDADCSDQSDESLEQCGRQPVIHTKCP
  ASEIQCGSGECIHKKWRCDGDPDCKDGSDEVNCPSRTCRPDQFECEDGSCIHGSRQCNGI
  RDCVDGSDEVNCKNVNQCLGPGKFKCRSGECIDISKVCNQEQDCRDWSDEPLKECHINEC
  LVNNGGCSHICKDLVIGYECDCAAGFELIDRKTCGDIDECQNPGICSQICINLKGGYKCE
  CSRGYQMDLATGVCKAVGKEPSLIFTNRRDIRKIGLERKEYIQLVEQLRNTVALDADIAA
  QKLFWADLSQKAIFSASIDDKVGRHVKMIDNVYNPAAIAVDWVYKTIYWTDAASKTISVA
  TLDGTKRKFLFNSDLREPASIAVDPLSGFVYWSDWGEPAKIEKAGMNGFDRRPLVTADIQ
  WPNGITLDLIKSRLYWLDSKLHMLSSVDLNGQDRRIVLKSLEFLAHPLALTIFEDRVYWI
  DGENEAVYGANKFTGSELATLVNNLNDAQDIIVYHELVQPSGKNWCEEDMENGGCEYLCL
  PAPQINDHSPKYTCSCPSGYNVEENGRDCQSTATTVTYSETKDTNTTEISATSGLVPGGI
  NVTTAVSEVSVPPKGTSAAWAILPLLLLVMAAVGGYLMWRNWQHKNMKSMNFDNPVYLKT
  TEEDLSIDIGRHSASVGHTYPAISVVSTDDDLA
• Function: Multifunctional cell surface receptor that binds VLDL and transports it into cells by endocytosis and therefore plays an important role in energy metabolism. Binds also to a wide range of other molecules including Reelin/RELN or apolipoprotein E/APOE-containing ligands as well as clusterin/CLU. In the off-state of the pathway, forms homooligomers or heterooligomers with LRP8. Upon binding to ligands, homooligomers are rearranged to higher order receptor clusters that transmit the extracellular RELN signal to intracellular signaling processes by binding to DAB1. This interaction results in phosphorylation of DAB1 leading to the ultimate cell responses required for the correct positioning of newly generated neurons. Later, mediates a stop signal for migrating neurons, preventing them from entering the marginal zone; (Microbial infection) Acts as a receptor for Semliki Forest virus.
• Tissue Specificity: Abundant in heart and skeletal muscle; also ovary and kidney; not in liver.
• KEGG Pathway:
  Spinocerebellar ataxia (hsa05017)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  VLDLR internalisation and degradation (R-HSA-8866427)
  VLDL clearance (R-HSA-8964046)
  Reelin signalling pathway (R-HSA-8866376)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1	DISBHBD6	Definitive	Autosomal recessive	[1]
Cerebellar ataxia, intellectual disability, and dysequilibrium	DIS9923V	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Very low-density lipoprotein receptor affects the response to substance of Temozolomide.	[32]
DTI-015	DMXZRW0	Approved	Very low-density lipoprotein receptor affects the response to substance of DTI-015.	[32]
Furosemide	DMMQ8ZG	Approved	Very low-density lipoprotein receptor increases the Renal failure ADR of Furosemide.	[33]
PMID27977313-Compound-29	DMIF7KG	Patented	Very low-density lipoprotein receptor increases the Lipid metabolism disorder ADR of PMID27977313-Compound-29.	[33]

38 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 Very low-density lipoprotein receptor.	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Very low-density lipoprotein receptor.	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Very low-density lipoprotein receptor.	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Very low-density lipoprotein receptor.	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Very low-density lipoprotein receptor.	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Very low-density lipoprotein receptor.	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Very low-density lipoprotein receptor.	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Very low-density lipoprotein receptor.	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Very low-density lipoprotein receptor.	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Very low-density lipoprotein receptor.	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Very low-density lipoprotein receptor.	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Very low-density lipoprotein receptor.	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Very low-density lipoprotein receptor.	[14]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Very low-density lipoprotein receptor.	[15]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Very low-density lipoprotein receptor.	[16]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Very low-density lipoprotein receptor.	[17]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Very low-density lipoprotein receptor.	[18]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Very low-density lipoprotein receptor.	[19]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Very low-density lipoprotein receptor.	[18]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Very low-density lipoprotein receptor.	[18]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Very low-density lipoprotein receptor.	[18]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the expression of Very low-density lipoprotein receptor.	[10]
Racecadotril	DMFOTZ7	Approved	Racecadotril increases the expression of Very low-density lipoprotein receptor.	[20]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Very low-density lipoprotein receptor.	[21]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Very low-density lipoprotein receptor.	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Very low-density lipoprotein receptor.	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Very low-density lipoprotein receptor.	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Very low-density lipoprotein receptor.	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Very low-density lipoprotein receptor.	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Very low-density lipoprotein receptor.	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Very low-density lipoprotein receptor.	[26]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Very low-density lipoprotein receptor.	[27]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Very low-density lipoprotein receptor.	[18]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Very low-density lipoprotein receptor.	[28]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Very low-density lipoprotein receptor.	[20]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Very low-density lipoprotein receptor.	[29]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Very low-density lipoprotein receptor.	[30]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Very low-density lipoprotein receptor.	[31]

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