Target Information
| Target General Information | Top | |||||
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| Target ID |
T03691
(Former ID: TTDC00130)
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| Target Name |
Leukotriene A-4 hydrolase (LTA4H)
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| Synonyms |
Leukotriene A4 hydrolase; Leukotriene A(4)Leukotriene A-4 hydrolase hydrolase; Leukotriene A(4) hydrolase; LTA4; LTA-H; LTA-4hydrolase; LTA-4 hydrolase
Click to Show/Hide
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| Gene Name |
LTA4H
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Acute myeloid leukaemia [ICD-11: 2A60] | |||||
| Function |
Has also aminopeptidase activity. Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4.
Click to Show/Hide
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| BioChemical Class |
Ether bond hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.3.2.6
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| Sequence |
MPEIVDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRSLVLDTKDL
TIEKVVINGQEVKYALGERQSYKGSPMEISLPIALSKNQEIVIEISFETSPKSSALQWLT PEQTSGKEHPYLFSQCQAIHCRAILPCQDTPSVKLTYTAEVSVPKELVALMSAIRDGETP DPEDPSRKIYKFIQKVPIPCYLIALVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETES MLKIAEDLGGPYVWGQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISH SWTGNLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFNALGGWGELQNSVKTFGET HPFTKLVVDLTDIDPDVAYSSVPYEKGFALLFYLEQLLGGPEIFLGFLKAYVEKFSYKSI TTDDWKDFLYSYFKDKVDVLNQVDWNAWLYSPGLPPIKPNYDMTLTNACIALSQRWITAK EDDLNSFNATDLKDLSSHQLNEFLAQTLQRAPLPLGHIKRMQEVYNFNAINNSEIRFRWL RLCIQSKWEDAIPLALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKASMHPVT AMLVGKDLKVD Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T01Z6D | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Bestatin | Drug Info | Approved | Acute myeloid leukaemia | [2], [3] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | LYS006 | Drug Info | Phase 2 | Ulcerative colitis | [4] | |
| 2 | Acebilustat | Drug Info | Phase 1 | Chronic blistering skin disorder | [5] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | DG051 | Drug Info | Discontinued in Phase 2 | Myocardial infarction | [6], [7] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 66 Inhibitor drugs | + | ||||
| 1 | Bestatin | Drug Info | [1] | |||
| 2 | LYS006 | Drug Info | [8] | |||
| 3 | Acebilustat | Drug Info | [5] | |||
| 4 | DG051 | Drug Info | [9], [10] | |||
| 5 | (4-(thiophen-2-yl)phenyl)methanamine | Drug Info | [11], [12] | |||
| 6 | (4-fluorophenyl)(pyridin-4-yl)methanone | Drug Info | [11] | |||
| 7 | (R)-2-((4-benzylphenoxy)methyl)piperidine | Drug Info | [13] | |||
| 8 | (R)-2-((4-phenoxyphenoxy)methyl)piperidine | Drug Info | [13] | |||
| 9 | (R)-2-(4-Benzylphenoxymethyl)pyrrolidine | Drug Info | [12] | |||
| 10 | (R)-N-benzyl-4-(pyrrolidin-2-ylmethoxy)aniline | Drug Info | [11], [14] | |||
| 11 | (R/S)-2-((4-benzylphenoxy)methyl)piperazine | Drug Info | [13] | |||
| 12 | (R/S)-2-((4-benzylphenoxy)methyl)piperidine | Drug Info | [13] | |||
| 13 | (R/S)-2-((4-phenoxyphenoxy)methyl)piperidine | Drug Info | [13] | |||
| 14 | (S)-2-((4-phenoxyphenoxy)methyl)piperidine | Drug Info | [13] | |||
| 15 | 1-(2,2'-bithiophen-5-yl)methanamine | Drug Info | [11] | |||
| 16 | 1-(4-Phenoxyphenyl)piperazine | Drug Info | [12] | |||
| 17 | 1-(pentyloxy)-4-phenoxybenzene | Drug Info | [15] | |||
| 18 | 1-butoxy-4-phenoxybenzene | Drug Info | [15] | |||
| 19 | 1-[4-(4-Iodophenoxy)phenyl]piperazine | Drug Info | [12] | |||
| 20 | 1-[4-(Benzothiazol-2-yloxy)benzyl]piperidin-4-ol | Drug Info | [16] | |||
| 21 | 2-(4-benzylphenoxy)ethanamine | Drug Info | [15] | |||
| 22 | 2-(4-phenoxyphenoxy)ethanamine | Drug Info | [15] | |||
| 23 | 2-(4-Piperidin-1-ylmethylphenoxy)benzothiazole | Drug Info | [16] | |||
| 24 | 2-(7-(benzyloxy)-1H-indol-3-yl)ethanamine | Drug Info | [17] | |||
| 25 | 2-Amino-N-[4-(phenylmethoxy)phenyl]-acetamide | Drug Info | [11], [18] | |||
| 26 | 2-[4-(2-Azepan-1-ylethoxy)phenoxy]benzooxazole | Drug Info | [16] | |||
| 27 | 2-[4-(2-Azepan-1-ylethoxy)phenoxy]benzothiazole | Drug Info | [16] | |||
| 28 | 2-[4-(2-Morpholin-4-ylethoxy)phenoxy]benzooxazole | Drug Info | [16] | |||
| 29 | 2-[4-(2-Piperidin-1-ylethyl)phenoxy]benzothiazole | Drug Info | [16] | |||
| 30 | 3-(Benzyloxy)Pyridin-2-Amine | Drug Info | [19] | |||
| 31 | 4-(2-amino-1,3-thiazol-4-yl)phenol | Drug Info | [11] | |||
| 32 | 4-(4-(pentyloxy)phenoxy)phenol | Drug Info | [15] | |||
| 33 | 4-(4-butoxyphenoxy)phenol | Drug Info | [15] | |||
| 34 | 4-(4-propoxyphenoxy)phenol | Drug Info | [15] | |||
| 35 | 4-amino-N-[4-(benzyloxy)phenyl]butanamide | Drug Info | [11], [18] | |||
| 36 | 4-[2-(4-Benzylphenoxy)ethyl]pyridine | Drug Info | [12] | |||
| 37 | 4S-4,5-Diamino-N-(4-phenoxyphenyl)pentanamide | Drug Info | [18] | |||
| 38 | 5-[2-(1H-pyrrol-1-yl)ethoxy]-1H-indole | Drug Info | [11] | |||
| 39 | 5-[2-(4-hydroxyphenyl)ethyl]benzene-1,3-diol | Drug Info | [11] | |||
| 40 | 8(S)-amino-2(R)-methyl-7-oxononanoic acid | Drug Info | [20] | |||
| 41 | Acetate Ion | Drug Info | [19] | |||
| 42 | JNJ-10392980 | Drug Info | [16] | |||
| 43 | N-(pyridin-3-ylmethyl)aniline | Drug Info | [11] | |||
| 44 | N-methyl-1-(2-thiophen-2-ylphenyl)methanamine | Drug Info | [11] | |||
| 45 | N1-[4-(Phenylmethoxy)phenyl]-D-aspartamine | Drug Info | [18] | |||
| 46 | N1-[4-(Phenylmethoxy)phenyl]-D-glutamine | Drug Info | [18] | |||
| 47 | N1-[4-(Phenylmethoxy)phenyl]-L-aspartamine | Drug Info | [18] | |||
| 48 | N1-[4-(Phenylmethoxy)phenyl]-L-glutamine | Drug Info | [18] | |||
| 49 | N4-[4-(Phenylmethoxy)phenyl]-L-aspartamine | Drug Info | [18] | |||
| 50 | N5-(4-Phenoxyphenyl)-L-glutamine | Drug Info | [18] | |||
| 51 | N5-[(4-Phenoxy)-3-pyridyl]-L-glutamamide | Drug Info | [18] | |||
| 52 | N5-[4-(1H-pyrrol-1-yl)phenyl]-L-glutamamide | Drug Info | [18] | |||
| 53 | N5-[4-(2-methylphenoxy)phenyl]-L-glutamamide | Drug Info | [18] | |||
| 54 | N5-[4-(2-Oxo-3-phenylpropoxy)phenyl]-L-glutamine | Drug Info | [18] | |||
| 55 | N5-[4-(2-phenylethoxy)phenyl]-L-glutamine | Drug Info | [18] | |||
| 56 | N5-[4-(3-methylphenoxy)phenyl]-L-glutamamide | Drug Info | [18] | |||
| 57 | N5-[4-(3-Phenylpropoxy)phenyl]-L-glutamine | Drug Info | [18] | |||
| 58 | N5-[4-(4-(3-Furyl)phenoxy)phenyl]-L-glutamamide | Drug Info | [18] | |||
| 59 | N5-[4-(4-methylphenoxy)phenyl]-L-glutamamide | Drug Info | [18] | |||
| 60 | N5-[4-(N-Phenylamino)phenyl]-L-glutamine | Drug Info | [18] | |||
| 61 | N5-[4-(Phenylmethoxy)phenyl]-D-glutamine | Drug Info | [18] | |||
| 62 | N5-[4-(Phenylmethoxy)phenyl]-L-glutamamide | Drug Info | [18] | |||
| 63 | N5-[4-(Phenylmethoxy)phenyl]-L-glutamine | Drug Info | [18] | |||
| 64 | N5-[4-Benzylphenyl]-L-glutamamide | Drug Info | [18] | |||
| 65 | N6-[4-(4-methylphenoxy)phenyl]-L-homoglutamine | Drug Info | [18] | |||
| 66 | SA-6541 | Drug Info | [21] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Bestatin | Ligand Info | |||||
| Structure Description | Leukotriene A4 hydrolase in complex with fragment 5-hydroxyindole and bestatin | PDB:3FUH | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [14] |
| PDB Sequence |
VDTCSLASPA
13 SVCRTKHLHL23 RCSVDFTRRT33 LTGTAALTVQ43 SQEDNLRSLV53 LDTKDLTIEK 63 VVINGQEVKY73 ALGERQSYKG83 SPMEISLPIA93 LSKNQEIVIE103 ISFETSPKSS 113 ALQWLTPEQT123 SGKEHPYLFS133 QCQAIHCRAI143 LPCQDTPSVK153 LTYTAEVSVP 163 KELVALMSAI173 RDGETPDPED183 PSRKIYKFIQ193 KVPIPCYLIA203 LVVGALESRQ 213 IGPRTLVWSE223 KEQVEKSAYE233 FSETESMLKI243 AEDLGGPYVW253 GQYDLLVLPP 263 SFPYGGMENP273 CLTFVTPTLL283 AGDKSLSNVI293 AHEISHSWTG303 NLVTNKTWDH 313 FWLNEGHTVY323 LERHICGRLF333 GEKFRHFNAL343 GGWGELQNSV353 KTFGETHPFT 363 KLVVDLTDID373 PDVAYSSVPY383 EKGFALLFYL393 EQLLGGPEIF403 LGFLKAYVEK 413 FSYKSITTDD423 WKDFLYSYFK433 DKVDVLNQVD443 WNAWLYSPGL453 PPIKPNYDMT 463 LTNACIALSQ473 RWITAKEDDL483 NSFNATDLKD493 LSSHQLNEFL503 AQTLQRAPLP 513 LGHIKRMQEV523 YNFNAINNSE533 IRFRWLRLCI543 QSKWEDAIPL553 ALKMATEQGR 563 MKFTRPLFKD573 LAAFDKSHDQ583 AVRTYQEHKA593 SMHPVTAMLV603 GKDLKVD |
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GLN134
3.663
GLN136
2.780
ALA137
4.077
TYR267
3.300
GLY268
2.750
GLY269
3.239
MET270
3.368
GLU271
2.609
ASN291
3.873
VAL292
4.003
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Captopril | Ligand Info | |||||
| Structure Description | Structure of human Leukotriene A4 hydrolase in complex with inhibitor captopril | PDB:4DPR | ||||
| Method | X-ray diffraction | Resolution | 2.02 Å | Mutation | No | [22] |
| PDB Sequence |
VDTCSLASPA
13 SVCRTKHLHL23 RCSVDFTRRT33 LTGTAALTVQ43 SQEDNLRSLV53 LDTKDLTIEK 63 VVINGQEVKY73 ALGERQSYKG83 SPMEISLPIA93 LSKNQEIVIE103 ISFETSPKSS 113 ALQWLTPEQT123 SGKEHPYLFS133 QCQAIHCRAI143 LPCQDTPSVK153 LTYTAEVSVP 163 KELVALMSAI173 RDGETPDPED183 PSRKIYKFIQ193 KVPIPCYLIA203 LVVGALESRQ 213 IGPRTLVWSE223 KEQVEKSAYE233 FSETESMLKI243 AEDLGGPYVW253 GQYDLLVLPP 263 SFPYGGMENP273 CLTFVTPTLL283 AGDKSLSNVI293 AHEISHSWTG303 NLVTNKTWDH 313 FWLNEGHTVY323 LERHICGRLF333 GEKFRHFNAL343 GGWGELQNSV353 KTFGETHPFT 363 KLVVDLTDID373 PDVAYSSVPY383 EKGFALLFYL393 EQLLGGPEIF403 LGFLKAYVEK 413 FSYKSITTDD423 WKDFLYSYFK433 DKVDVLNQVD443 WNAWLYSPGL453 PPIKPNYDMT 463 LTNACIALSQ473 RWITAKEDDL483 NSFNATDLKD493 LSSHQLNEFL503 AQTLQRAPLP 513 LGHIKRMQEV523 YNFNAINNSE533 IRFRWLRLCI543 QSKWEDAIPL553 ALKMATEQGR 563 MKFTRPLFKD573 LAAFDKSHDQ583 AVRTYQEHKA593 SMHPVTAMLV603 GKDLKVD |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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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| Arachidonic acid metabolism | hsa00590 | Affiliated Target |
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| Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.60E-01 | Radiality | 1.24E+01 | Clustering coefficient | 1.00E+00 |
| Neighborhood connectivity | 4.50E+00 | Topological coefficient | 6.43E-01 | Eccentricity | 14 |
| 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 Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 1 BioCyc Pathways | + | ||||
| 1 | Leukotriene biosynthesis | |||||
| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Arachidonic acid metabolism | |||||
| 2 | Metabolic pathways | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Arachidonic Acid Metabolism | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Arachidonic acid metabolism | |||||
| 2 | Eicosanoid Synthesis | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 2 | 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: 5151). | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | ClinicalTrials.gov (NCT04074590) A Randomized, Multi-center, Subject and Investigator-blinded, Placebo-controlled, Parallel-group Study to Assess the Efficacy Safety and Tolerability of LYS006 in Patients With Mild to Moderate Ulcerative Colitis. U.S.National Institutes of Health. | |||||
| REF 5 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 6 | 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: 6548). | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024010) | |||||
| REF 8 | Discovery of LYS006, a Potent and Highly Selective Inhibitor of Leukotriene A(4) Hydrolase. J Med Chem. 2021 Feb 25;64(4):1889-1903. | |||||
| REF 9 | BAY x 1005 attenuates atherosclerosis in apoE/LDLR - double knockout mice. J Physiol Pharmacol. 2007 Sep;58(3):583-8. | |||||
| REF 10 | Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA. 2005 May 11;293(18):2245-56. | |||||
| REF 11 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 12 | Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of ... J Med Chem. 2010 Jan 28;53(2):573-85. | |||||
| REF 13 | Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds. Bioorg Med Chem Lett. 2010 May 1;20(9):2851-4. | |||||
| REF 14 | Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography. J Med Chem. 2009 Aug 13;52(15):4694-715. | |||||
| REF 15 | Activation and inhibition of leukotriene A4 hydrolase aminopeptidase activity by diphenyl ether and derivatives. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6549-52. | |||||
| REF 16 | Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69. | |||||
| REF 17 | Discovery of multitarget inhibitors by combining molecular docking with common pharmacophore matching. J Med Chem. 2008 Dec 25;51(24):7882-8. | |||||
| REF 18 | Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase. Bioorg Med Chem. 2008 May 1;16(9):4963-83. | |||||
| REF 19 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 20 | Isolation and structure of leukotriene-A4 hydrolase inhibitor: 8(S)-amino-2(R)-methyl-7-oxononanoic acid produced by Streptomyces diastaticus. J Nat Prod. 1996 Oct;59(10):962-4. | |||||
| REF 21 | Synthesis and biological evaluation of N-mercaptoacylcysteine derivatives as leukotriene A4 hydrolase inhibitors. Bioorg Med Chem Lett. 2009 Jan 15;19(2):442-6. | |||||
| REF 22 | Capturing LTA(4) hydrolase in action: Insights to the chemistry and dynamics of chemotactic LTB(4) synthesis. Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):9689-9694. | |||||
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