Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS44RIC)

• DOT Name: Oxidized low-density lipoprotein receptor 1 (OLR1)
• Synonyms: Ox-LDL receptor 1; C-type lectin domain family 8 member A; Lectin-like oxidized LDL receptor 1; LOX-1; Lectin-like oxLDL receptor 1; hLOX-1; Lectin-type oxidized LDL receptor 1
• Gene Name: OLR1
• UniProt ID: OLR1_HUMAN
• PDB ID: 1YPO; 1YPQ; 1YPU; 1YXJ; 1YXK; 3VLG; 6TL7; 6TL9; 6TLA; 7R8U; 7W5D; 7XMP
• Pfam ID: PF00059 ; PF08391
• Sequence:
  MTFDDLKIQTVKDQPDEKSNGKKAKGLQFLYSPWWCLAAATLGVLCLGLVVTIMVLGMQL
  SQVSDLLTQEQANLTHQKKKLEGQISARQQAEEASQESENELKEMIETLARKLNEKSKEQ
  MELHHQNLNLQETLKRVANCSAPCPQDWIWHGENCYLFSSGSFNWEKSQEKCLSLDAKLL
  KINSTADLDFIQQAISYSSFPFWMGLSRRNPSYPWLWEDGSPLMPHLFRVRGAVSQTYPS
  GTCAYIQRGAVYAENCILAAFSICQKKANLRAQ
• Function: Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that induces vascular endothelial cell activation and dysfunction, resulting in pro-inflammatory responses, pro-oxidative conditions and apoptosis. Its association with oxLDL induces the activation of NF-kappa-B through an increased production of intracellular reactive oxygen and a variety of pro-atherogenic cellular responses including a reduction of nitric oxide (NO) release, monocyte adhesion and apoptosis. In addition to binding oxLDL, it acts as a receptor for the HSP70 protein involved in antigen cross-presentation to naive T-cells in dendritic cells, thereby participating in cell-mediated antigen cross-presentation. Also involved in inflammatory process, by acting as a leukocyte-adhesion molecule at the vascular interface in endotoxin-induced inflammation. Also acts as a receptor for advanced glycation end (AGE) products, activated platelets, monocytes, apoptotic cells and both Gram-negative and Gram-positive bacteria; (Microbial infection) May serve as a receptor for adhesin A variant 3 (nadA) of N.meningitidis.
• Tissue Specificity: Expressed at high level in endothelial cells and vascular-rich organs such as placenta, lung, liver and brain, aortic intima, bone marrow, spinal cord and substantia nigra. Also expressed at the surface of dendritic cells. Widely expressed at intermediate and low level.
• KEGG Pathway:
  PPAR sig.ling pathway (hsa03320)
  Phagosome (hsa04145)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Oxidized low-density lipoprotein receptor 1 (OLR1) decreases the response to substance of Resveratrol.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[8]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[9]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[1]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[1]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[1]
Nifedipine	DMSVOZT	Approved	Nifedipine decreases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[10]
Aldosterone	DM9S2JW	Approved	Aldosterone increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[11]
HMPL-004	DM29XGY	Phase 3	HMPL-004 increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[12]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[12]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[15]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[17]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[18]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug affects the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[19]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[1]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[12]
PAF	DMRZAQW	Investigative	PAF increases the expression of Oxidized low-density lipoprotein receptor 1 (OLR1).	[20]

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 decreases the methylation of Oxidized low-density lipoprotein receptor 1 (OLR1).	[14]

References

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• [11] Aldosterone augments LOX-1-mediated low-density lipoprotein uptake in human umbilical artery endothelial cells. Pharmacol Rep. 2010 Mar-Apr;62(2):311-8. doi: 10.1016/s1734-1140(10)70271-1.
• [12] Mapping the dynamics of Nrf2 antioxidant and NFB inflammatory responses by soft electrophilic chemicals in human liver cells defines the transition from adaptive to adverse responses. Toxicol In Vitro. 2022 Oct;84:105419. doi: 10.1016/j.tiv.2022.105419. Epub 2022 Jun 17.
• [13] Curcuminoids distinctly exhibit antioxidant activities and regulate expression of scavenger receptors and heme oxygenase-1. Mol Nutr Food Res. 2013 Sep;57(9):1598-610. doi: 10.1002/mnfr.201200227. Epub 2013 Feb 5.
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• [20] Oxidized phospholipid: POVPC binds to platelet-activating-factor receptor on human macrophagesImplications in atherosclerosis. Atherosclerosis. 2006 Oct;188(2):433-43.
• [21] Resveratrol attenuates oxidized LDL-evoked Lox-1 signaling and consequently protects against apoptotic insults to cerebrovascular endothelial cells. J Cereb Blood Flow Metab. 2011 Mar;31(3):842-54. doi: 10.1038/jcbfm.2010.180. Epub 2010 Oct 13.