Target Information
Target General Information | Top | |||||
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Target ID |
T49630
(Former ID: TTDR00861)
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Target Name |
Lectin-like oxidized LDL receptor (OLR1)
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Synonyms |
hLOX-1; Oxidized low-density lipoprotein receptor 1; Oxidized low-density lipoprotein receptor; Oxidised low density lipoprotein (Lectin-like) receptor 1; Ox-LDL receptor 1; Lectin-type oxidized LDL receptor 1; Lectin-type oxidized LDL receptor; Lectin-like oxidized low-density lipoprotein receptor-1; Lectin-like oxidized LDL receptor-1; Lectin-like oxidized LDL receptor 1; Lectin-like oxLDL receptor 1; LOX1; LOX-1; CLEC8A; C-type lectin domain family 8 member A
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Gene Name |
OLR1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Cardiovascular disease [ICD-11: BA00-BE2Z] | |||||
2 | Coronary atherosclerosis [ICD-11: BA80] | |||||
Function |
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. Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells.
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UniProt ID | ||||||
Sequence |
MTFDDLKIQTVKDQPDEKSNGKKAKGLQFLYSPWWCLAAATLGVLCLGLVVTIMVLGMQL
SQVSDLLTQEQANLTHQKKKLEGQISARQQAEEASQESENELKEMIETLARKLNEKSKEQ MELHHQNLNLQETLKRVANCSAPCPQDWIWHGENCYLFSSGSFNWEKSQEKCLSLDAKLL KINSTADLDFIQQAISYSSFPFWMGLSRRNPSYPWLWEDGSPLMPHLFRVRGAVSQTYPS GTCAYIQRGAVYAENCILAAFSICQKKANLRAQ Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T10ICM |
Drugs and Modes of Action | Top | |||||
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Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | RG7418 | Drug Info | Discontinued in Phase 1 | Arteriosclerosis | [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | RG7418 | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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PPAR signaling pathway | hsa03320 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
Phagosome | hsa04145 | Affiliated Target |
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Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy |
Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 4.14E-05 |
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Closeness centrality | 2.09E-01 | Radiality | 1.37E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 3.85E+01 | Topological coefficient | 5.00E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
References | Top | |||||
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REF 1 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
REF 2 | ClinicalTrials.gov (NCT04610892) A Phase IIB, Randomized, Double Blinded, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of MEDI6570 in Participants With a Prior Myocardial Infarction and Persistent Inflammation. U.S.National Institutes of Health. | |||||
REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019399) |
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