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.
Click to Show/Hide
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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] | |||
| 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 | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| 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 | |||||
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| 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. | |||||
| REF 42 | Quantitative analytical methods for the determination of a new hypertension drug, CGS 25462, and its metabolites (CGS 25659 and CGS 24592) in human plasma by high-performance liquid chromatography. JChromatogr B Biomed Sci Appl. 1998 Mar 20;706(2):287-94. | |||||
| REF 43 | Antihypertensive effects of fasidotril, a dual inhibitor of neprilysin and angiotensin-converting enzyme, in rats and humans. Hypertension. 2000 May;35(5):1148-53. | |||||
| REF 44 | Omapatrilat.Bristol-Myers Squibb.Curr Opin Investig Drugs.2001 Oct;2(10):1414-22. | |||||
| REF 45 | Effects of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase on the vasopressor response to exogenous angiot... J Cardiovasc Pharmacol. 1998 Mar;31(3):408-17. | |||||
| REF 46 | Comparative effects of the dual ACE-NEP inhibitor MDL-100,240 and ramipril on hypertension and cardiovascular disease in endogenous angiotensin II-... Am J Hypertens. 2002 Feb;15(2 Pt 1):181-8. | |||||
| REF 47 | The antinociceptive effects of SCH-32615, a neutral endopeptidase (enkephalinase) inhibitor, microinjected into the periaqueductal, ventral medulla and amygdala. Brain Res. 1990 Jun 18;520(1-2):123-30. | |||||
| REF 48 | Pharmacology of SCH 34826, an orally active enkephalinase inhibitor analgesic. J Pharmacol Exp Ther. 1988 Jun;245(3):829-38. | |||||
| REF 49 | Endopeptidase 24.11 inhibition by SCH 42495 in essential hypertension. Hypertension. 1993 Jul;22(1):119-26. | |||||
| REF 50 | Candoxatril, an orally active neutral endopeptidase inhibitor, raises plasma atrial natriuretic factor and is natriuretic in essential hypertension. J Hypertens. 1992 Mar;10(3):271-7. | |||||
| REF 51 | Potent non-peptidic dual inhibitors of endothelin-converting enzyme and neutral endopeptidase 24.11, Bioorg. Med. Chem. Lett. 7(8):1059-1064 (1997). | |||||
| REF 52 | Oral administration of an inhibitor of endothelin-converting enzyme attenuates cerebral vasospasm following experimental subarachnoid haemorrhage in rabbits. Clin Sci (Lond). 2002 Aug;103 Suppl 48:414S-417S. | |||||
| REF 53 | Phosphinic tripeptides as dual angiotensin-converting enzyme C-domain and endothelin-converting enzyme-1 inhibitors. J Med Chem. 2010 Jan 14;53(1):208-20. | |||||
| REF 54 | Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43. | |||||
| REF 55 | Evaluation of SQ 28,603, an inhibitor of neutral endopeptidase, in conscious monkeys. Can J Physiol Pharmacol. 1991 Oct;69(10):1609-17. | |||||
| REF 56 | Design and synthesis of an orally active macrocyclic neutral endopeptidase 24.11 inhibitor. J Med Chem. 1993 Nov 26;36(24):3821-8. | |||||
| REF 57 | Modelling of aldose reductase inhibitory activity of pyrrol-1-yl-acetic acid derivatives by means of multivariate statistics. Med Chem. 2005 Jul;1(4):321-6. | |||||
| REF 58 | 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: 1611). | |||||
| REF 59 | Neprilysin, a novel target for ultraviolet B regulation of melanogenesis via melanocortins. J Invest Dermatol. 2000 Sep;115(3):381-7. | |||||
| REF 60 | Thiol-based angiotensin-converting enzyme 2 inhibitors: P1 modifications for the exploration of the S1 subsite. Bioorg Med Chem Lett. 2008 Jan 15;18(2):732-7. | |||||
| REF 61 | Reversal of cardiac hypertrophy and fibrosis by S21402, a dual inhibitor of neutral endopeptidase and angiotensin converting enzyme in SHRs. J Hypertens. 2000 Jun;18(6):749-55. | |||||
| REF 62 | Renal and vascular effects of S21402, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase, in healthy subjects with hypovol... Clin Pharmacol Ther. 2002 Jun;71(6):468-78. | |||||
| REF 63 | Beneficial renal and cardiac effects of vasopeptidase inhibition with S21402 in heart failure. Hypertension. 2000 Dec;36(6):1105-11. | |||||
| REF 64 | Thiorphan enhances bradykinin-induced vascular relaxation in hypoxic/hyperkalaemic porcine coronary artery. J Pharm Pharmacol. 2003 Mar;55(3):339-45. | |||||
| REF 65 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
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