Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T35734
(Former ID: TTDR01203)
|
|||||
| Target Name |
Soluble epoxide hydrolase (EPHX2)
|
|||||
| Synonyms |
Bifunctional epoxide hydrolase 2
Click to Show/Hide
|
|||||
| Gene Name |
EPHX2
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Hypertension [ICD-11: BA00-BA04] | |||||
| 2 | Chronic obstructive pulmonary disease [ICD-11: CA22] | |||||
| Function |
Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides (By similarity). Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid and 12-phosphonooxy-octadec-9E-enoic acid.
Click to Show/Hide
|
|||||
| BioChemical Class |
Ether bond hydrolase
|
|||||
| UniProt ID | ||||||
| Sequence |
MTLRAAVFDLDGVLALPAVFGVLGRTEEALALPRGLLNDAFQKGGPEGATTRLMKGEITL
SQWIPLMEENCRKCSETAKVCLPKNFSIKEIFDKAISARKINRPMLQAALMLRKKGFTTA ILTNTWLDDRAERDGLAQLMCELKMHFDFLIESCQVGMVKPEPQIYKFLLDTLKASPSEV VFLDDIGANLKPARDLGMVTILVQDTDTALKELEKVTGIQLLNTPAPLPTSCNPSDMSHG YVTVKPRVRLHFVELGSGPAVCLCHGFPESWYSWRYQIPALAQAGYRVLAMDMKGYGESS APPEIEEYCMEVLCKEMVTFLDKLGLSQAVFIGHDWGGMLVWYMALFYPERVRAVASLNT PFIPANPNMSPLESIKANPVFDYQLYFQEPGVAEAELEQNLSRTFKSLFRASDESVLSMH KVCEAGGLFVNSPEEPSLSRMVTEEEIQFYVQQFKKSGFRGPLNWYRNMERNWKWACKSL GRKILIPALMVTAEKDFVLVPQMSQHMEDWIPHLKRGHIEDCGHWTQMDKPTEVNQILIK WLDSDARNPPVVSKM Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A01328 ; BADD_A04278 | |||||
| HIT2.0 ID | T63YQM | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | AR9281 | Drug Info | Phase 2 | Hypertension | [2] | |
| 2 | GSK2256294 | Drug Info | Phase 1 | Chronic obstructive pulmonary disease | [3] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 90 Inhibitor drugs | + | ||||
| 1 | AR9281 | Drug Info | [1] | |||
| 2 | 1-(1-Propionylpiperidin-4-yl)-3-m-tolylurea | Drug Info | [5] | |||
| 3 | 1-(1-Propionylpiperidin-4-yl)-3-o-tolylurea | Drug Info | [5] | |||
| 4 | 1-(1-Propionylpiperidin-4-yl)-3-p-tolylurea | Drug Info | [5] | |||
| 5 | 1-(3-(3-morpholinopropoxy)phenyl)-3-phenylurea | Drug Info | [6] | |||
| 6 | 1-(3-Chloro-phenyl)-3-(4-hydroxy-decyl)-urea | Drug Info | [7] | |||
| 7 | 1-(3-Chloro-phenyl)-3-cyclohexyl-urea | Drug Info | [7] | |||
| 8 | 1-(4-(3-morpholinopropoxy)phenyl)-3-phenylurea | Drug Info | [6] | |||
| 9 | 1-adamantan-1-yl-3-((R)-1-phenyl-ethyl)-urea | Drug Info | [8] | |||
| 10 | 1-adamantan-1-yl-3-(1-benzyl-piperidin-4-yl)-urea | Drug Info | [9] | |||
| 11 | 1-adamantan-1-yl-3-(1-butyl-piperidin-4-yl)-urea | Drug Info | [9] | |||
| 12 | 1-adamantan-1-yl-3-(1-propyl-piperidin-4-yl)-urea | Drug Info | [9] | |||
| 13 | 1-Adamantan-1-yl-3-(2-hydroxy-phenyl)-urea | Drug Info | [10] | |||
| 14 | 1-adamantan-1-yl-3-(2-hydroxyethyl)urea | Drug Info | [11] | |||
| 15 | 1-Adamantan-1-yl-3-(2-methoxy-phenyl)-urea | Drug Info | [10] | |||
| 16 | 1-Adamantan-1-yl-3-(3-hydroxy-phenyl)-urea | Drug Info | [10] | |||
| 17 | 1-adamantan-1-yl-3-(3-hydroxypropyl)urea | Drug Info | [11] | |||
| 18 | 1-Adamantan-1-yl-3-(4-hydroxy-decyl)-urea | Drug Info | [7] | |||
| 19 | 1-Adamantan-1-yl-3-(4-hydroxy-phenyl)-urea | Drug Info | [10] | |||
| 20 | 1-adamantan-1-yl-3-(4-hydroxybutyl)urea | Drug Info | [11] | |||
| 21 | 1-Adamantan-1-yl-3-(4-methoxy-phenyl)-urea | Drug Info | [10] | |||
| 22 | 1-adamantan-1-yl-3-(4-pentyloxybutyl)urea | Drug Info | [11] | |||
| 23 | 1-adamantan-1-yl-3-(4-pentyloxycylclohexyl)urea | Drug Info | [11] | |||
| 24 | 1-adamantan-1-yl-3-(5-butoxypentyl)urea | Drug Info | [11] | |||
| 25 | 1-adamantan-1-yl-3-(6-propyloxyhexyl)urea | Drug Info | [11] | |||
| 26 | 1-adamantan-1-yl-3-piperidin-4-yl-urea | Drug Info | [9] | |||
| 27 | 1-adamantan-1-yl-3-piperidin-4-ylmethyl-urea | Drug Info | [9] | |||
| 28 | 1-adamantan-1-yl-3-[4-(4-fluorophenoxy)butyl]urea | Drug Info | [1] | |||
| 29 | 1-Cycloheptyl-3-(1-propionylpiperidin-4-yl)urea | Drug Info | [5] | |||
| 30 | 1-Cyclohexyl-3-(1-propionylpiperidin-4-yl)urea | Drug Info | [5] | |||
| 31 | 1-Cyclohexyl-3-(4-methoxy-phenyl)-urea | Drug Info | [7] | |||
| 32 | 1-Cyclohexyl-3-phenethyl-urea | Drug Info | [7] | |||
| 33 | 1-Cyclohexyl-3-phenyl-urea | Drug Info | [7] | |||
| 34 | 1-Octyl-3-(1-propionylpiperidin-4-yl)urea | Drug Info | [5] | |||
| 35 | 1-Phenyl-3-(1-propionylpiperidin-4-yl)urea | Drug Info | [5] | |||
| 36 | 12-(3-Adamantan-1-yl-ureido)-dodeca noic acid | Drug Info | [12] | |||
| 37 | 12-(3-n-Hexylureido)dodec-8(Z)-enoic acid | Drug Info | [13] | |||
| 38 | 12-(3-n-Pentylureidooxy)dodec-8(Z)-enoic acid | Drug Info | [13] | |||
| 39 | 13-(3-n-Pentylthioureido)tridec-8(Z)-enoic Acid | Drug Info | [13] | |||
| 40 | 13-(3-n-Pentylureido)tridec-8(E)-enoic acid | Drug Info | [13] | |||
| 41 | 13-(3-n-Pentylureido)tridec-8-ynoic acid | Drug Info | [13] | |||
| 42 | 13-(3-Pentyluredo)tridec-8(Z)-enoic acid | Drug Info | [13] | |||
| 43 | 13-(5-n-Pentylfuran-2-yl)tridec-8(Z)-enoic acid | Drug Info | [13] | |||
| 44 | 13-(N-Isopropylheptanamido)tridec-8(Z)-enoic acid | Drug Info | [13] | |||
| 45 | 13-(N-Methyl-n-heptnamido)tridec-8(Z)-enoic acid | Drug Info | [13] | |||
| 46 | 13-(n-Pentylcarbamoyloxy)tridec-8(Z)-enoic acid | Drug Info | [13] | |||
| 47 | 13-n-Heptanamidotridec-5-ynoic acid | Drug Info | [13] | |||
| 48 | 13-n-Heptanamidotridec-8(Z)-enoic acid | Drug Info | [13] | |||
| 49 | 14-(n-Hexylamino)-14-oxotetradec-8(Z)-enoic acid | Drug Info | [13] | |||
| 50 | 16-(3-Ethylureido)hexadec-11(Z)-enoic acid | Drug Info | [13] | |||
| 51 | 2-Cyclohexyl-N-(4-methoxy-phenyl)-acetamide | Drug Info | [7] | |||
| 52 | 2-Cyclohexyl-N-phenethyl-acetamide | Drug Info | [7] | |||
| 53 | 2-Cyclohexyl-N-phenyl-acetamide | Drug Info | [7] | |||
| 54 | 3-(3-Adamantan-1-yl-ureido)-benzoic acid | Drug Info | [10] | |||
| 55 | 4,4-Diphenyl-N-(pyridin-3-yl)-butyramide | Drug Info | [14] | |||
| 56 | 4-(3-Adamantan-1-yl-ureido)-benzoic acid | Drug Info | [10] | |||
| 57 | 4-(3-cyclohexylureido)butanoic acid | Drug Info | [15], [16] | |||
| 58 | 6-amino-N-(2,4-dichlorobenzyl)nicotinamide | Drug Info | [17] | |||
| 59 | 6-amino-N-(3,3-diphenylpropyl)nicotinamide | Drug Info | [17] | |||
| 60 | 6-{[(CYCLOHEXYLAMINO)CARBONYL]AMINO}HEXANOIC ACID | Drug Info | [15] | |||
| 61 | 9-(3-n-Pentylureido)non-4(Z)-enoic acid | Drug Info | [13] | |||
| 62 | 9-(3-n-Pentylureido)non-4-ynoic acid | Drug Info | [13] | |||
| 63 | Cis-1-adamantan-1-yl-3-(4-methoxycyclohexyl)urea | Drug Info | [1] | |||
| 64 | Dodecanoic acid adamantan-1-ylamide | Drug Info | [7] | |||
| 65 | Methyl 14-(3-n-butylureido)tetradec-8(Z)-enoate | Drug Info | [13] | |||
| 66 | Methyl 4-(3-cyclohexylureido)butanoate | Drug Info | [16] | |||
| 67 | Methyl 6-(3-cyclohexylureido)hexanoate | Drug Info | [16] | |||
| 68 | N,N'-dicyclohexyl-urea | Drug Info | [1] | |||
| 69 | N-(3,3-Diphenyl-propyl)-2-pyridine-3-ylacetamide | Drug Info | [14] | |||
| 70 | N-(3,3-Diphenyl-propyl)-isonicotinamide | Drug Info | [14] | |||
| 71 | N-(3,3-diphenyl-propyl)-nicotinamide | Drug Info | [14] | |||
| 72 | N-(3-Chloro-phenyl)-2-cyclohexyl-acetamide | Drug Info | [7] | |||
| 73 | N-(3-Phenyl-propyl)-nicotinamide | Drug Info | [14] | |||
| 74 | N-(4,4-Diphenyl-butyl)-nicotinamide | Drug Info | [14] | |||
| 75 | N-(biphenyl-3-yl)benzo[d]isoxazol-3-amine | Drug Info | [18] | |||
| 76 | N-(biphenyl-4-yl)benzo[d]isoxazol-3-amine | Drug Info | [18] | |||
| 77 | N-(naphthalen-1-yl)benzo[d]isoxazol-3-amine | Drug Info | [18] | |||
| 78 | N-adamantyl-N'-cyclohexylurea | Drug Info | [1] | |||
| 79 | N-benzyl-6-(3,3,3-trifluoropropoxy)nicotinamide | Drug Info | [17] | |||
| 80 | N-Cyclohexyl-2-(4-methoxy-phenyl)-acetamide | Drug Info | [7] | |||
| 81 | N-Cyclohexyl-2-phenyl-acetamide | Drug Info | [7] | |||
| 82 | N-Cyclohexyl-4-phenyl-butyramide | Drug Info | [7] | |||
| 83 | N-Cyclohexyl-N'-(4-Iodophenyl)Urea | Drug Info | [19] | |||
| 84 | N-Cyclohexyl-N'-(Propyl)Phenyl Urea | Drug Info | [15] | |||
| 85 | N-Cyclohexyl-N'-Decylurea | Drug Info | [15] | |||
| 86 | N-[(CYCLOHEXYLAMINO)CARBONYL]GLYCINE | Drug Info | [15] | |||
| 87 | N-[3,3-Bis-(4-fluorophenyl)-propyl]-benzamide | Drug Info | [14] | |||
| 88 | N-[3,3-Bis-(4-fluorophenyl)-propyl]-nicotinamide | Drug Info | [14] | |||
| 89 | Trans,trans-1,3-bis-(4-hydroxycyclohexyl)urea | Drug Info | [1] | |||
| 90 | [4-(3-Adamantan-1-yl-ureido)-phenyl]-acetic acid | Drug Info | [10] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | GSK2256294 | Drug Info | [3], [4] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 4-(3-cyclohexylureido)butanoic acid | Ligand Info | |||||
| Structure Description | Human soluble epoxide hydrolase 4-(3-cyclohexyluriedo)-butyric acid complex | PDB:1ZD3 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [20] |
| PDB Sequence |
TLRAAVFDLD
11 GVLALPAVFG21 VLGRTEEALA31 LPRGLLNDAF41 QKGGPEGATT51 RLMKGEITLS 61 QWIPLMEENC71 RKCSETAKVC81 LPKNFSIKEI91 FDKAISARKI101 NRPMLQAALM 111 LRKKGFTTAI121 LTNTWLDDRA131 ERDGLAQLMC141 ELKMHFDFLI151 ESCQVGMVKP 161 EPQIYKFLLD171 TLKASPSEVV181 FLDDIGANLK191 PARDLGMVTI201 LVQDTDTALK 211 ELEKVTGIQL221 LNTPAPLPTS229 CNPSDMSHGY239 VTVKPRVRLH249 FVELGSGPAV 259 CLCHGFPESW269 YSWRYQIPAL279 AQAGYRVLAM289 DMKGYGESSA299 PPEIEEYCME 309 VLCKEMVTFL319 DKLGLSQAVF329 IGHDWGGMLV339 WYMALFYPER349 VRAVASLNTP 359 FIPANPNMSP369 LESIKANPVF379 DYQLYFQEPG389 VAEAELEQNL399 SRTFKSLFRA 409 SDESVLSMHK420 VCEAGGLFVN430 SPEEPSLSRM440 VTEEEIQFYV450 QQFKKSGFRG 460 PLNWYRNMER470 NWKWACKSLG480 RKILIPALMV490 TAEKDFVLVP500 QMSQHMEDWI 510 PHLKRGHIED520 CGHWTQMDKP530 TEVNQILIKW540 LDSDARN
|
|||||
|
|
||||||
| Ligand Name: N-Cyclohexyl-N'-(4-Iodophenyl)Urea | Ligand Info | |||||
| Structure Description | Human soluble Epoxide Hydrolase- N-cyclohexyl-N'-(4-iodophenyl)urea complex | PDB:1VJ5 | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [21] |
| PDB Sequence |
TLRAAVFDLD
11 GVLALPAVFG21 VLGRTEEALA31 LPRGLLNDAF41 QKGGPEGATT51 RLMKGEITLS 61 QWIPLMEENC71 RKCSETAKVC81 LPKNFSIKEI91 FDKAISARKI101 NRPMLQAALM 111 LRKKGFTTAI121 LTNTWLDDRA131 ERDGLAQLMC141 ELKMHFDFLI151 ESCQVGMVKP 161 EPQIYKFLLD171 TLKASPSEVV181 FLDDIGANLK191 PARDLGMVTI201 LVQDTDTALK 211 ELEKVTGIQL221 LNTPAPLPTS229 CNPSDMSHGY239 VTVKPRVRLH249 FVELGSGPAV 259 CLCHGFPESW269 YSWRYQIPAL279 AQAGYRVLAM289 DMKGYGESSA299 PPEIEEYCME 309 VLCKEMVTFL319 DKLGLSQAVF329 IGHDWGGMLV339 WYMALFYPER349 VRAVASLNTP 359 FIPANPNMSP369 LESIKANPVF379 DYQLYFQEPG389 VAEAELEQNL399 SRTFKSLFRA 409 SDESVLSMHK420 VCEAGGLFVN430 SPEEPSLSRM440 VTEEEIQFYV450 QQFKKSGFRG 460 PLNWYRNMER470 NWKWACKSLG480 RKILIPALMV490 TAEKDFVLVP500 QMSQHMEDWI 510 PHLKRGHIED520 CGHWTQMDKP530 TEVNQILIKW540 LDSDARN
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
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
|
|
|
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.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Arachidonic acid metabolism | hsa00590 | Affiliated Target |
|
| Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
| Peroxisome | hsa04146 | Affiliated Target |
|
| Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy | ||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 5.30E-05 |
|---|---|---|---|---|---|
| Closeness centrality | 1.62E-01 | Radiality | 1.24E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 8.25E+00 | Topological coefficient | 3.30E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "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 | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Arachidonic acid metabolism | |||||
| 2 | Metabolic pathways | |||||
| 3 | Peroxisome | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Arachidonic Acid Metabolism | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | Metapathway biotransformation | |||||
| 2 | Arachidonate Epoxygenase / Epoxide Hydrolase | |||||
| 3 | Arachidonic acid metabolism | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Orally bioavailable potent soluble epoxide hydrolase inhibitors. J Med Chem. 2007 Aug 9;50(16):3825-40. | |||||
| REF 2 | ClinicalTrials.gov (NCT00847899) Evaluation of Soluble Epoxide Hydrolase (s-EH) Inhibitor in Patients With Mild to Moderate Hypertension and Impaired Glucose Tolerance. U.S. National Institutes of Health. | |||||
| REF 3 | Soluble epoxide hydrolase inhibition does not prevent cardiac remodeling and dysfunction after aortic constriction in rats and mice. J Cardiovasc Pharmacol. 2013 Apr;61(4):291-301. | |||||
| REF 4 | In vitro and in vivo characterization of a novel soluble epoxide hydrolase inhibitor. Prostaglandins Other Lipid Mediat. 2013 Jul-Aug;104-105:25-31. | |||||
| REF 5 | 1-Aryl-3-(1-acylpiperidin-4-yl)urea inhibitors of human and murine soluble epoxide hydrolase: structure-activity relationships, pharmacokinetics, a... J Med Chem. 2010 Oct 14;53(19):7067-75. | |||||
| REF 6 | Unsymmetrical non-adamantyl N,N'-diaryl urea and amide inhibitors of soluble expoxide hydrolase. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4259-63. | |||||
| REF 7 | Optimization of amide-based inhibitors of soluble epoxide hydrolase with improved water solubility. J Med Chem. 2005 May 19;48(10):3621-9. | |||||
| REF 8 | Solid-phase combinatorial approach for the optimization of soluble epoxide hydrolase inhibitors. Bioorg Med Chem Lett. 2006 Nov 15;16(22):5773-7. | |||||
| REF 9 | Synthesis and SAR of conformationally restricted inhibitors of soluble epoxide hydrolase. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5212-6. | |||||
| REF 10 | Salicylate-urea-based soluble epoxide hydrolase inhibitors with high metabolic and chemical stabilities. Bioorg Med Chem Lett. 2009 Mar 15;19(6):1784-9. | |||||
| REF 11 | 1,3-disubstituted ureas functionalized with ether groups are potent inhibitors of the soluble epoxide hydrolase with improved pharmacokinetic prope... J Med Chem. 2007 Oct 18;50(21):5217-26. | |||||
| REF 12 | Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement. J Med Chem. 2009 Aug 27;52(16):5009-12. | |||||
| REF 13 | 14,15-Epoxyeicosa-5,8,11-trienoic acid (14,15-EET) surrogates containing epoxide bioisosteres: influence upon vascular relaxation and soluble epoxi... J Med Chem. 2009 Aug 27;52(16):5069-75. | |||||
| REF 14 | Structure-based optimization of arylamides as inhibitors of soluble epoxide hydrolase. J Med Chem. 2009 Oct 8;52(19):5880-95. | |||||
| REF 15 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 16 | Peptidyl-urea based inhibitors of soluble epoxide hydrolases. Bioorg Med Chem Lett. 2006 Oct 15;16(20):5439-44. | |||||
| REF 17 | Design and synthesis of substituted nicotinamides as inhibitors of soluble epoxide hydrolase. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5864-8. | |||||
| REF 18 | A strategy of employing aminoheterocycles as amide mimics to identify novel, potent and bioavailable soluble epoxide hydrolase inhibitors. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5716-21. | |||||
| REF 19 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 20 | Human soluble epoxide hydrolase: structural basis of inhibition by 4-(3-cyclohexylureido)-carboxylic acids. Protein Sci. 2006 Jan;15(1):58-64. | |||||
| REF 21 | Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis. Biochemistry. 2004 Apr 27;43(16):4716-23. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.