Target Information
| Target General Information | Top | |||||
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| Target ID |
T05409
(Former ID: TTDS00449)
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| Target Name |
Neutral endopeptidase (MME)
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| Synonyms |
Skin fibroblast elastase; SFE; Neutral endopeptidase 24.11; Neprilysin; NEP protein; Enkephalinase; EPN; Common acute lymphocytic leukemia antigen; CD10; CALLA; Atriopeptidase
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| Gene Name |
MME
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Heart failure [ICD-11: BD10-BD1Z] | |||||
| Function |
Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers. Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.24.11
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| Sequence |
MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSS
DCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKD VLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGA SWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKE ACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLY NKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILT KYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNME NAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERI GYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAA VVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKD GDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYR AYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRII GTLQNSAEFSEAFHCRKNSYMNPEKKCRVW Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A02149 | |||||
| HIT2.0 ID | T06MXL | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | LCZ696 | Drug Info | Approved | Heart failure | [1] | |
| Clinical Trial Drug(s) | [+] 13 Clinical Trial Drugs | + | ||||
| 1 | Candoxatril | Drug Info | Phase 3 | Hypertension | [2], [3] | |
| 2 | Gallopamil | Drug Info | Phase 2 | Asthma | [4] | |
| 3 | Sampatrilat | Drug Info | Phase 2 | Hypotension | [5] | |
| 4 | SLV 306 | Drug Info | Phase 2 | Acute decompensated heart failure | [6], [7] | |
| 5 | SLV-334 | Drug Info | Phase 2 | Brain injury | [8] | |
| 6 | VX-15 | Drug Info | Phase 2 | Huntington disease | [9] | |
| 7 | CART-10 cells | Drug Info | Phase 1 | Acute lymphoblastic leukaemia | [10] | |
| 8 | CD10-CART | Drug Info | Phase 1 | leukaemia | [11] | |
| 9 | Debio 0827 | Drug Info | Phase 1 | Chronic pain | [12] | |
| 10 | GW-796406 | Drug Info | Phase 1 | Hypotension | [13] | |
| 11 | Pfizer 4 | Drug Info | Phase 1 | Female sexual arousal dysfunction | [14] | |
| 12 | SLV-338 | Drug Info | Phase 1 | Cardiovascular disease | [15] | |
| 13 | TD-0714 | Drug Info | Phase 1 | Heart failure | [16] | |
| Discontinued Drug(s) | [+] 15 Discontinued Drugs | + | ||||
| 1 | Ilepatril | Drug Info | Discontinued in Phase 2/3 | Diabetic nephropathy | [17] | |
| 2 | CGS-25462 | Drug Info | Discontinued in Phase 2 | Hypertension | [18] | |
| 3 | Fasidotril | Drug Info | Discontinued in Phase 2 | Hypotension | [19], [20] | |
| 4 | Gemopatrilat | Drug Info | Discontinued in Phase 2 | Hypotension | [21] | |
| 5 | M-100240 | Drug Info | Discontinued in Phase 2 | Hypotension | [22] | |
| 6 | SCH-32615 | Drug Info | Discontinued in Phase 2 | Pain | [23] | |
| 7 | Sch-34826 | Drug Info | Discontinued in Phase 2 | Hypertension | [24] | |
| 8 | SCH-42495 | Drug Info | Discontinued in Phase 2 | Hypotension | [25] | |
| 9 | Candoxatrilat | Drug Info | Discontinued in Phase 1 | Heart failure | [26], [27] | |
| 10 | BMS-182657 | Drug Info | Terminated | Cardiovascular disease | [28] | |
| 11 | CGS-26393 | Drug Info | Terminated | Heart disease | [29] | |
| 12 | CGS-30440 | Drug Info | Terminated | Hypertension | [30] | |
| 13 | GW-660511 | Drug Info | Terminated | Hypertension | [31] | |
| 14 | Omapatrilat | Drug Info | Terminated | Hypertension | [32] | |
| 15 | SQ-28603 | Drug Info | Terminated | Hypertension | [33] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Modulator | [+] 19 Modulator drugs | + | ||||
| 1 | LCZ696 | Drug Info | [1] | |||
| 2 | Sampatrilat | Drug Info | [5], [37] | |||
| 3 | SLV 306 | Drug Info | [8], [38] | |||
| 4 | SLV-334 | Drug Info | [39] | |||
| 5 | GW-796406 | Drug Info | [36] | |||
| 6 | SLV-338 | Drug Info | [15], [41] | |||
| 7 | Ilepatril | Drug Info | [17] | |||
| 8 | CGS-25462 | Drug Info | [42] | |||
| 9 | Fasidotril | Drug Info | [43] | |||
| 10 | Gemopatrilat | Drug Info | [44] | |||
| 11 | M-100240 | Drug Info | [45], [46] | |||
| 12 | Sch-34826 | Drug Info | [48] | |||
| 13 | BMS-182657 | Drug Info | [28] | |||
| 14 | CGS-26393 | Drug Info | [52] | |||
| 15 | CGS-30440 | Drug Info | [30] | |||
| 16 | GW-660511 | Drug Info | [31] | |||
| 17 | Omapatrilat | Drug Info | [32] | |||
| 18 | SQ-28603 | Drug Info | [55] | |||
| 19 | RB-105 | Drug Info | [61], [62], [63] | |||
| Inhibitor | [+] 20 Inhibitor drugs | + | ||||
| 1 | Candoxatril | Drug Info | [34], [35] | |||
| 2 | Gallopamil | Drug Info | [36] | |||
| 3 | VX-15 | Drug Info | [40] | |||
| 4 | Debio 0827 | Drug Info | [12] | |||
| 5 | Pfizer 4 | Drug Info | [14] | |||
| 6 | TD-0714 | Drug Info | [16] | |||
| 7 | SCH-32615 | Drug Info | [8], [47] | |||
| 8 | SCH-42495 | Drug Info | [8], [49] | |||
| 9 | Candoxatrilat | Drug Info | [8], [50] | |||
| 10 | CGS-26303 | Drug Info | [51] | |||
| 11 | SCH-54470 | Drug Info | [53] | |||
| 12 | SQ-26332 | Drug Info | [54] | |||
| 13 | 9-Mercaptomethyl-10-oxo-azecane-2-carboxylic acid | Drug Info | [56] | |||
| 14 | CGS-314447 | Drug Info | [51] | |||
| 15 | fasidotrilat | Drug Info | [57] | |||
| 16 | LBQ657 | Drug Info | [58] | |||
| 17 | Phosphoramidon | Drug Info | [59] | |||
| 18 | PMID18078750C1b | Drug Info | [60] | |||
| 19 | Thiorphan | Drug Info | [64] | |||
| 20 | [2(R,S)-2-Sulfanylheptanoyl]-Phe-Ala | Drug Info | [65] | |||
| CAR-T-Cell-Therapy | [+] 1 CAR-T-Cell-Therapy drugs | + | ||||
| 1 | CART-10 cells | Drug Info | [10] | |||
| CAR-T-Cell-Therapy(Dual specific) | [+] 1 CAR-T-Cell-Therapy(Dual specific) drugs | + | ||||
| 1 | CD10-CART | Drug Info | [11] | |||
| 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: Sampatrilat | Ligand Info | |||||
| Structure Description | Crystal structure of Neprilysin in complex with Sampatrilat. | PDB:6XVP | ||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [66] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
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ARG102
2.293
TYR103
4.830
GLY104
4.777
PHE106
3.044
ASP107
2.897
ARG110
3.045
ILE535
4.358
ASN542
2.189
ALA543
2.856
PHE544
3.066
TYR545
3.509
SER546
4.914
ILE558
4.209
PHE563
4.714
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| Ligand Name: Omapatrilat | Ligand Info | |||||
| Structure Description | Crystal structure of Neprilysin in complex with Omapatrilat. | PDB:6SUK | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [66] |
| PDB Sequence |
DDGICKSSDC
61 IKSAARLIQN71 MDATTEPCTD81 FFKYACGGWL91 KRNVIPETSS101 RYGNFDILRD 111 ELEVVLKDVL121 QEPKTEDIVA131 VQKAKALYRS141 CINESAIDSR151 GGEPLLKLLP 161 DIYGWPVATE171 NWEQKYGASW181 TAEKAIAQLN191 SKYGKKVLIN201 LFVGTDDKNS 211 VNHVIHIDQP221 RLGLPSRDYY231 ECTGIYKEAC241 TAYVDFMISV251 ARLIRQEERL 261 PIDENQLALE271 MNKVMELEKE281 IANATAKPED291 RNDPMLLYNK301 MTLAQIQNNF 311 SLEINGKPFS321 WLNFTNEIMS331 TVNISITNEE341 DVVVYAPEYL351 TKLKPILTKY 361 SARDLQNLMS371 WRFIMDLVSS381 LSRTYKESRN391 AFRKALYGTT401 SETATWRRCA 411 NYVNGNMENA421 VGRLYVEAAF431 AGESKHVVED441 LIAQIREVFI451 QTLDDLTWMD 461 AETKKRAEEK471 ALAIKERIGY481 PDDIVSNDNK491 LNNEYLELNY501 KEDEYFENII 511 QNLKFSQSKQ521 LKKLREKVDK531 DEWISGAAVV541 NAFYSSGRNQ551 IVFPAGILQP 561 PFFSAQQSNS571 LNYGGIGMVI581 GHEITHGFDD591 NGRNFNKDGD601 LVDWWTQQSA 611 SNFKEQSQCM621 VYQYGNFSWD631 LAGGQHLNGI641 NTLGENIADN651 GGLGQAYRAY 661 QNYIKKNGEE671 KLLPGLDLNH681 KQLFFLNFAQ691 VWCGTYRPEY701 AVNSIKTDVH 711 SPGNFRIIGT721 LQNSAEFSEA731 FHCRKNSYMN741 PEKKCRVW
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ARG102
2.321
PHE106
1.872
ARG110
2.259
VAL541
4.402
ASN542
2.152
ALA543
2.659
PHE544
4.229
ILE558
2.741
PHE563
2.746
MET579
2.638
VAL580
2.656
HIS583
2.406
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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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| Renin-angiotensin system | hsa04614 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Hematopoietic cell lineage | hsa04640 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Protein digestion and absorption | hsa04974 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 1.18E-04 |
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| Closeness centrality | 2.18E-01 | Radiality | 1.38E+01 | Clustering coefficient | 1.67E-01 |
| Neighborhood connectivity | 3.03E+01 | Topological coefficient | 2.63E-01 | Eccentricity | 11 |
| 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-regulating Transcription Factors | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Renin-angiotensin system | |||||
| 2 | Hematopoietic cell lineage | |||||
| 3 | Protein digestion and absorption | |||||
| 4 | Alzheimer's disease | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | EGFR1 Signaling Pathway | |||||
| 2 | TGF_beta_Receptor Signaling Pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Metabolism of Angiotensinogen to Angiotensins | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | Metabolism of Angiotensinogen to Angiotensins | |||||
| 2 | Primary Focal Segmental Glomerulosclerosis FSGS | |||||
| 3 | Alzheimers Disease | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. | |||||
| 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: 6492). | |||||
| REF 3 | Drug information of Candoxatril, 2008. eduDrugs. | |||||
| REF 4 | ClinicalTrials.gov (NCT00896428) Effects of Gallopamil in Severe Asthma (REMODEL'ASTHME) in University Hospital, Bordeaux. | |||||
| REF 5 | Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects. Am J Hypertens. 1999 Jun;12(6):563-71. | |||||
| 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: 6506). | |||||
| REF 7 | ClinicalTrials.gov (NCT00160225) Study to Evaluate the Efficacy and Safety of Daglutril Compared to Placebo on Top of Losartan in Type 2 Diabetics With Overt Nephropathy and Well Controlled Hypertension. U.S. National Institutes of Health. | |||||
| REF 8 | The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans. Life Sci. 2012 Oct 15;91(13-14):743-8. | |||||
| REF 9 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 10 | ClinicalTrials.gov (NCT03291444) CAR-T Cells Combined With Peptide Specific Dendritic Cell in Relapsed/Refractory Leukemia/MDS | |||||
| REF 11 | ClinicalTrials.gov (NCT03407859) Sequential Treatment With CD20/CD22/CD10-CART After CD19-CART Treatment Base on MRD in Relapsed/Refractory B-ALL | |||||
| REF 12 | Clinical pipeline report, company report or official report of Debiopharm (2011). | |||||
| REF 13 | Mechanism of vasopeptidase inhibitor-induced plasma extravasation: comparison of omapatrilat and the novel neutral endopeptidase 24.11/angiotensin-... J Pharmacol Exp Ther. 2005 Dec;315(3):1306-13. | |||||
| REF 14 | Designing drugs for the treatment of female sexual dysfunction. Drug Discov Today. 2007 Sep;12(17-18):757-66. | |||||
| REF 15 | Renoprotective effects of combined endothelin-converting enzyme/neutral endopeptidase inhibitor SLV338 in acute and chronic experimental renal damage. Clin Lab. 2011;57(7-8):507-15. | |||||
| REF 16 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 17 | Ilepatril (AVE-7688), a vasopeptidase inhibitor for the treatment of hypertension. Curr Opin Investig Drugs. 2008 Mar;9(3):301-9. | |||||
| REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002979) | |||||
| REF 19 | 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: 6501). | |||||
| REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003997) | |||||
| REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009581) | |||||
| REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002832) | |||||
| REF 23 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002402) | |||||
| REF 24 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000196) | |||||
| REF 25 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002070) | |||||
| REF 26 | 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: 6491). | |||||
| REF 27 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001740) | |||||
| REF 28 | Cardiovascular effects of the novel dual inhibitor of neutral endopeptidase and angiotensin-converting enzyme BMS-182657 in experimental hypertension and heart failure. J Pharmacol Exp Ther. 1995 Nov;275(2):745-52. | |||||
| REF 29 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005940) | |||||
| REF 30 | Antihypertensive and natriuretic effects of CGS 30440, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase 24.11. J Pharmacol Exp Ther. 1998 Mar;284(3):974-82. | |||||
| REF 31 | The effects of Z13752A, a combined ACE/NEP inhibitor, on responses to coronary artery occlusion; a primary protective role for bradykinin. Br J Pharmacol. 2000 Feb;129(4):671-80. | |||||
| REF 32 | Omapatrilat, a dual angiotensin-converting enzyme and neutral endopeptidase inhibitor, prevents fatty streak deposit in apolipoprotein E-deficient mice. Atherosclerosis. 2001 Apr;155(2):291-5. | |||||
| REF 33 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000347) | |||||
| REF 34 | Neutral endopeptidase inhibitor suppresses the early phase of atrial electrical remodeling in a canine rapid atrial pacing model. Indian Pacing Electrophysiol J. 2008 Apr 1;8(2):102-13. | |||||
| REF 35 | Dual inhibition of angiotensin converting enzyme and neutral endopeptidase produces effective blood pressure control in spontaneously hypertensive rats. Bratisl Lek Listy. 2005;106(12):407-11. | |||||
| REF 36 | Mechanism of vasopeptidase inhibitor-induced plasma extravasation: comparison of omapatrilat and the novel neutral endopeptidase 24.11/angiotensin-converting enzyme inhibitor GW796406. J Pharmacol Exp Ther. 2005 Dec;315(3):1306-13. | |||||
| REF 37 | Sampatrilat Shire. Curr Opin Investig Drugs. 2002 Apr;3(4):578-81. | |||||
| REF 38 | Effect of single doses of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on pulmonary pressures in congestive heart failure. Am J Cardiol. 2004 Jul 15;94(2):237-9. | |||||
| REF 39 | Clinical trials in traumatic brain injury: past experience and current developments.Neurotherapeutics.2010 Jan;7(1):115-26. | |||||
| REF 40 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 41 | Endothelin-converting enzyme/neutral endopeptidase inhibitor SLV338 prevents hypertensive cardiac remodeling in a blood pressure-independent manner.Hypertension.2011 Apr;57(4):755-63. | |||||
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