Target Information
Target General Information | Top | |||||
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Target ID |
T55689
(Former ID: TTDR00917)
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Target Name |
Hormone sensitive lipase (LIPE)
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Synonyms |
Hormone-sensitive lipase; HSL
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Gene Name |
LIPE
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Pediculosis [ICD-11: 1G00] | |||||
Function |
In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production.
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BioChemical Class |
Carboxylic ester hydrolase
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UniProt ID | ||||||
EC Number |
EC 3.1.1.79
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Sequence |
MEPGSKSVSRSDWQPEPHQRPITPLEPGPEKTPIAQPESKTLQGSNTQQKPASNQRPLTQ
QETPAQHDAESQKEPRAQQKSASQEEFLAPQKPAPQQSPYIQRVLLTQQEAASQQGPGLG KESITQQEPALRQRHVAQPGPGPGEPPPAQQEAESTPAAQAKPGAKREPSAPTESTSQET PEQSDKQTTPVQGAKSKQGSLTELGFLTKLQELSIQRSALEWKALSEWVTDSESESDVGS SSDTDSPATMGGMVAQGVKLGFKGKSGYKVMSGYSGTSPHEKTSARNHRHYQDTASRLIH NMDLRTMTQSLVTLAEDNIAFFSSQGPGETAQRLSGVFAGVREQALGLEPALGRLLGVAH LFDLDPETPANGYRSLVHTARCCLAHLLHKSRYVASNRRSIFFRTSHNLAELEAYLAALT QLRALVYYAQRLLVTNRPGVLFFEGDEGLTADFLREYVTLHKGCFYGRCLGFQFTPAIRP FLQTISIGLVSFGEHYKRNETGLSVAASSLFTSGRFAIDPELRGAEFERITQNLDVHFWK AFWNITEMEVLSSLANMASATVRVSRLLSLPPEAFEMPLTADPTLTVTISPPLAHTGPGP VLVRLISYDLREGQDSEELSSLIKSNGQRSLELWPRPQQAPRSRSLIVHFHGGGFVAQTS RSHEPYLKSWAQELGAPIISIDYSLAPEAPFPRALEECFFAYCWAIKHCALLGSTGERIC LAGDSAGGNLCFTVALRAAAYGVRVPDGIMAAYPATMLQPAASPSRLLSLMDPLLPLSVL SKCVSAYAGAKTEDHSNSDQKALGMMGLVRRDTALLLRDFRLGASSWLNSFLELSGRKSQ KMSEPIAEPMRRSVSEAALAQPQGPLGTDSLKNLTLRDLSLRGNSETSSDTPEMSLSAET LSPSTPSDVNFLLPPEDAGEEAEAKNELSPMDRGLGVRAAFPEGFHPRRSSQGATQMPLY SSPIVKNPFMSPLLAPDSMLKSLPPVHIVACALDPMLDDSVMLARRLRNLGQPVTLRVVE DLPHGFLTLAALCRETRQAAELCVERIRLVLTPPAGAGPSGETGAAGVDGGCGGRH Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T82VBE |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | BENZYL BENZOATE | Drug Info | Approved | Infestations of lice and scabies | [1] | |
Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | PMID15026062C41 | Drug Info | Clinical trial | Pancreatitis | [2], [3] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | BENZYL BENZOATE | Drug Info | [1] | |||
2 | PMI-008 | Drug Info | [5] | |||
Inhibitor | [+] 7 Inhibitor drugs | + | ||||
1 | PMID15026062C41 | Drug Info | [2] | |||
2 | 2-(3-methoxybenzylthio)-2-phenylacetic acid | Drug Info | [4] | |||
3 | BIFENOX | Drug Info | [4] | |||
4 | ETHIOFENCARB | Drug Info | [4] | |||
5 | NCI-159878 | Drug Info | [4] | |||
6 | NCI-58425 | Drug Info | [4] | |||
7 | OXYBENZONE | Drug Info | [4] |
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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cAMP signaling pathway | hsa04024 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
AMPK signaling pathway | hsa04152 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Apelin signaling pathway | hsa04371 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Thermogenesis | hsa04714 | Affiliated Target |
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Class: Organismal Systems => Environmental adaptation | Pathway Hierarchy | ||
Insulin signaling pathway | hsa04910 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
Regulation of lipolysis in adipocytes | hsa04923 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
Aldosterone synthesis and secretion | hsa04925 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
Click to Show/Hide the Information of Affiliated Human Pathways |
Degree | 9 | Degree centrality | 9.67E-04 | Betweenness centrality | 1.63E-03 |
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Closeness centrality | 1.87E-01 | Radiality | 1.32E+01 | Clustering coefficient | 5.56E-02 |
Neighborhood connectivity | 3.67E+00 | Topological coefficient | 1.48E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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BioCyc | [+] 1 BioCyc Pathways | + | ||||
1 | Triacylglycerol degradation | |||||
KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
1 | cAMP signaling pathway | |||||
2 | AMPK signaling pathway | |||||
3 | Insulin signaling pathway | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Triacylglycerol metabolism | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Hormone-sensitive lipase (HSL)-mediated triacylglycerol hydrolysis | |||||
WikiPathways | [+] 6 WikiPathways | + | ||||
1 | Insulin Signaling | |||||
2 | Triacylglyceride Synthesis | |||||
3 | Lipid digestion, mobilization, and transport | |||||
4 | Adipogenesis | |||||
5 | Fatty Acid Beta Oxidation | |||||
6 | AMPK Signaling |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. | |||||
REF 2 | Carbazates as potent inhibitors of hormone-sensitive lipase. Bioorg Med Chem Lett. 2004 Apr 5;14(7):1741-4. | |||||
REF 3 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6702). | |||||
REF 4 | Combining ligand-based pharmacophore modeling, quantitative structure-activity relationship analysis and in silico screening for the discovery of n... J Med Chem. 2008 Oct 23;51(20):6478-94. | |||||
REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2593). |
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