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Article ; Online: Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus.

Tang, Wei-Jen

Trends in endocrinology and metabolism: TEM

2015 Volume 27, Issue 1, Page(s) 24–34

Abstract: Insulin-degrading enzyme (IDE) selectively degrades peptides, such as insulin, amylin, and amyloid β (Aβ) that form toxic aggregates, to maintain proteostasis. IDE defects are linked to the development of type 2 diabetes mellitus (T2DM) and Alzheimer's ... ...

Abstract	Insulin-degrading enzyme (IDE) selectively degrades peptides, such as insulin, amylin, and amyloid β (Aβ) that form toxic aggregates, to maintain proteostasis. IDE defects are linked to the development of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). Structural and biochemical analyses revealed the molecular basis for IDE-mediated destruction of amyloidogenic peptides and this information has been exploited to develop promising inhibitors of IDE to improve glucose homeostasis. However, the inhibition of IDE can also lead to glucose intolerance. In this review, I focus on recent advances regarding our understanding of the structure and function of IDE and the discovery of IDE inhibitors, as well as challenges in developing IDE-based therapy for human diseases, particularly T2DM.
MeSH term(s)	Alzheimer Disease/enzymology ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Diabetes Mellitus, Type 2/enzymology ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Glucose Intolerance ; Humans ; Insulin/metabolism ; Insulysin/metabolism ; Islet Amyloid Polypeptide/metabolism
Chemical Substances	Amyloid beta-Peptides ; Insulin ; Islet Amyloid Polypeptide ; Insulysin (EC 3.4.24.56)
Language	English
Publishing date	2015-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/j.tem.2015.11.003
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Zs.A 2999: Show issues

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Article ; Online: Impact of smoking on one year functional outcomes after thrombectomy for young stroke patients.

Peng, Szu-Hsiang / Lai, Yen-Jun / Lai, Wei-Jen / Li, Ai-Hsien / Yen, Ho-Hsian / Huang, Lih-Wen / Tang, Chih-Wei

Journal of neurointerventional surgery

2023 Volume 15, Issue e3, Page(s) e343–e348

Abstract: Background: The incidence of stroke in young patients (20-50 years old) has increased in recent decades. Unlike the use of good functional outcomes to evaluate prognosis, excellent functional outcomes are a better indicator of return to work among ... ...

Abstract	Background: The incidence of stroke in young patients (20-50 years old) has increased in recent decades. Unlike the use of good functional outcomes to evaluate prognosis, excellent functional outcomes are a better indicator of return to work among younger patients. The rate of return to work increases with time after stroke. This study investigated the short term (3 months) and long term (1 year) predictors of excellent functional outcomes in young patients after endovascular thrombectomy (EVT). Methods: We included young patients who underwent EVT for acute ischemic stroke (AIS) due to large vessel occlusion within 6 hours after stroke onset between 2015 and 2021. Patients with intracerebral hemorrhage on pretreatment CT were excluded. The associations between clinical, imaging, and procedure variables, and excellent functional outcomes were analyzed using univariate and multivariable logistic regression analyses. An excellent functional outcome was defined as a modified Rankin Scale score of ≤1. Results: Of the 361 patients with AIS eligible for EVT, 55 young patients (aged 24-50 years) were included. Of these, 36.4% and 41.8% achieved excellent functional outcomes at 3 and 12 months, respectively. Multivariate analysis revealed that smoking was the independent negative predictor of both 3 month (adjusted OR (aOR) 0.232, 95% CI 0.058 to 0.928; p=0.039) and 12 month (aOR 0.180, 95% CI 0.044 to 0.741; p=0.018) excellent functional outcomes. Conclusions: Current or former smoking habit was an independent negative predictor of both short term and long term excellent functional outcomes in young adults with AIS.
MeSH term(s)	Young Adult ; Humans ; Adult ; Middle Aged ; Ischemic Stroke/diagnostic imaging ; Ischemic Stroke/surgery ; Ischemic Stroke/etiology ; Brain Ischemia/diagnostic imaging ; Brain Ischemia/surgery ; Brain Ischemia/drug therapy ; Treatment Outcome ; Stroke/diagnostic imaging ; Stroke/surgery ; Stroke/drug therapy ; Thrombectomy/methods ; Endovascular Procedures/methods ; Smoking/adverse effects ; Smoking/epidemiology
Language	English
Publishing date	2023-12-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2514982-9
ISSN	1759-8486 ; 1759-8478
ISSN (online)	1759-8486
ISSN	1759-8478
DOI	10.1136/jnis-2022-019815
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Zs.A 6845: Show issues

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Article ; Online: The compensatory hypertrophy of transferred flexor hallucis longus tendon for insertional Achilles tendinopathy: a retrospective MRI study.

Liao, Wei-Jen / Tang, Shih-Chieh / Shih, Han-Ting / Su, Kuo-Chih / Tu, Kao-Chang / Wang, Shun-Ping

Scientific reports

2023 Volume 13, Issue 1, Page(s) 20475

Abstract: Flexor hallucis longus (FHL) transfer is an effective surgery in treating insertional Achilles tendinopathy (IAT). However, limited data exist regarding the post-surgery changes in the transferred FHL. The study aimed to compare the sequential changes ... ...

Abstract	Flexor hallucis longus (FHL) transfer is an effective surgery in treating insertional Achilles tendinopathy (IAT). However, limited data exist regarding the post-surgery changes in the transferred FHL. The study aimed to compare the sequential changes and hypertrophy of FHL after isolated FHL transfer (FHLT). We retrospectively enrolled patients who underwent isolated FHLT for insertional Achilles pathology from 2015 to 2020 and divided them into two groups based on whether reattachment of the residue Achilles stump to the FHL was performed or not. We recorded demographic characteristics, MRI parameters, and functional outcome. We also analyzed the correlation between the collected data and FHL hypertrophy. Results revealed no significant differences in most MRI parameters of FHL and functional outcomes between the groups. However, the fat distribution within the FHL showed significant reduction and notable 20.2% hypertrophy after FHLT. Interestingly, the hypertrophy of the FHL was significantly more pronounced in the non-reattached group. Furthermore, we observed a positive correlation between the follow-up period and FHL hypertrophy. In conclusion, the FHL demonstrated significant enlargement over time following FHLT. The compensatory hypertrophy of the transferred FHL was particularly evident and the cumulative incidences of FHL enlargement over time were higher in the non-reattached groupcompared to reattached group. However, both reattachment and non-reattachment of Achilles stump on FHL transfer for insertional Achilles tendinopathy carried similar postoperative functional outcomes.
MeSH term(s)	Humans ; Retrospective Studies ; Achilles Tendon/diagnostic imaging ; Achilles Tendon/surgery ; Tendon Transfer/methods ; Tendinopathy/diagnostic imaging ; Tendinopathy/surgery ; Magnetic Resonance Imaging ; Hypertrophy
Language	English
Publishing date	2023-11-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-47725-1
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Article: Impacts of COVID-19 pandemic on the collection and use of blood and blood components in Taiwan.

Hsu, Ling-I / Chen, Jen-Wei / Wei, Sheng-Tang / Hou, Sheng-Mou

Journal of the Formosan Medical Association = Taiwan yi zhi

2024

Abstract: Background: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the supply and transfusion of blood components. This study aims to evaluate changes in blood collection and transfusions during the period following the nationwide ... ...

Abstract	Background: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the supply and transfusion of blood components. This study aims to evaluate changes in blood collection and transfusions during the period following the nationwide Level 3 alert (May-July 2021). Methods: We retrieved usage data for red blood cells (RBC) from the Taiwan National Health Insurance (NHI) database 2019-2021. Results: During the Level 3 alert period, approximately 85% of COVID-19 cases (11,455/13,624) were in Taipei. In Taipei, blood collection declined by 26.34% and RBC transfusions decreased by 17.14% compared to pre-pandemic levels. RBC usage decreased across all service types, with a significant decrease observed in hematology/oncology by 15.62% (-483 patients, -2,425 units). In non-Taipei regions, blood collection declined by 12.54%, rebounding around one month earlier than in Taipei. The decline in RBC transfusions occurred one month later than in Taipei, with a much lower magnitude (4.57%). Strain on the blood supply occurred in May and June in both Taipei and non-Taipei regions. Among 7,532 hospitalized COVID-19 patients, approximately 6.9% patients required a total of 1,873 RBC transfusions. The rapid increase in COVID-19 inpatients did not significantly increase the burden of blood demands. Summary: During the Level 3 alert, the most significant decline in both RBC collection and transfusions was observed in Taipei. In non-Taipei regions, the decrease in RBC use was only marginal. Notably, there was a significant decrease in RBC use in hematology/oncology in Taipei. This study supports transfusion specialists in seeking efficient ways to address similar future challenges.
Language	English
Publishing date	2024-03-27
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2096659-3
ISSN	1876-0821 ; 0929-6646
ISSN (online)	1876-0821
ISSN	0929-6646
DOI	10.1016/j.jfma.2024.03.017
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Zs.B 1041: Show issues

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Article ; Online: Structural analysis of Mycobacterium tuberculosis M13 metalloprotease Zmp1 open states.

Liang, Wenguang G / Mancl, Jordan M / Zhao, Minglei / Tang, Wei-Jen

Structure (London, England : 1993)

2020 Volume 29, Issue 7, Page(s) 709–720.e3

Abstract: Zinc metalloprotease 1 (Zmp1), a Mycobacterium tuberculosis 75 kDa secreted enzyme, mediates key stages of tuberculosis disease progression. The biological activity of Zmp1 presumably stems from its ability to degrade bacterium- and/or host-derived ... ...

Abstract	Zinc metalloprotease 1 (Zmp1), a Mycobacterium tuberculosis 75 kDa secreted enzyme, mediates key stages of tuberculosis disease progression. The biological activity of Zmp1 presumably stems from its ability to degrade bacterium- and/or host-derived peptides. The crystal structures of Zmp1 and related M13 metalloproteases, such as neprilysin and endothelin-converting enzyme-1 were determined only in the closed conformation, which cannot capture substrates or release proteolytic products. Thus, the mechanisms of substrate binding and selectivity remain elusive. Here we report two open-state cryo-EM structures of Zmp1, revealed by our SAXS analysis to be the dominant states in solution. Our structural analyses reveal how ligand binding induces a conformational switch in four linker regions to drive the rigid body motion of the D1 and D2 domains, which form the sizable catalytic chamber. Furthermore, they offer insights into the catalytic cycle and mechanism of substrate recognition of M13 metalloproteases for future therapeutic innovations.
MeSH term(s)	Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Cryoelectron Microscopy ; Ligands ; Metalloproteases/chemistry ; Metalloproteases/metabolism ; Models, Molecular ; Mycobacterium tuberculosis/enzymology ; Protein Binding ; Protein Conformation ; Protein Domains ; Scattering, Small Angle ; X-Ray Diffraction
Chemical Substances	Bacterial Proteins ; Ligands ; Metalloproteases (EC 3.4.-) ; Zmp1 protein, Mycobacterium tuberculosis (EC 3.4.-)
Language	English
Publishing date	2020-12-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1213087-4
ISSN	1878-4186 ; 0969-2126
ISSN (online)	1878-4186
ISSN	0969-2126
DOI	10.1016/j.str.2020.12.002
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Zs.A 4141: Show issues

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Article ; Online: Degradation of Alzheimer's Amyloid-β by a Catalytically Inactive Insulin-Degrading Enzyme.

Sahoo, Bikash R / Panda, Pritam Kumar / Liang, Wenguang / Tang, Wei-Jen / Ahuja, Rajeev / Ramamoorthy, Ayyalusamy

Journal of molecular biology

2021 Volume 433, Issue 13, Page(s) 166993

Abstract: It is known that insulin-degrading-enzyme (IDE) plays a crucial role in the clearance of Alzheimer's amyloid-β (Aβ). The cysteine-free IDE mutant (cf-E111Q-IDE) is catalytically inactive against insulin, but its effect on Aβ degradation is unknown that ... ...

Abstract	It is known that insulin-degrading-enzyme (IDE) plays a crucial role in the clearance of Alzheimer's amyloid-β (Aβ). The cysteine-free IDE mutant (cf-E111Q-IDE) is catalytically inactive against insulin, but its effect on Aβ degradation is unknown that would help in the allosteric modulation of the enzyme activity. Herein, the degradation of Aβ(1-40) by cf-E111Q-IDE via a non-chaperone mechanism is demonstrated by NMR and LC-MS, and the aggregation of fragmented peptides is characterized using fluorescence and electron microscopy. cf-E111Q-IDE presented a reduced effect on the aggregation kinetics of Aβ(1-40) when compared with the wild-type IDE. Whereas LC-MS and diffusion ordered NMR spectroscopy revealed the generation of Aβ fragments by both wild-type and cf-E111Q-IDE. The aggregation propensities and the difference in the morphological phenotype of the full-length Aβ(1-40) and its fragments are explained using multi-microseconds molecular dynamics simulations. Notably, our results reveal that zinc binding to Aβ(1-40) inactivates cf-E111Q-IDE's catalytic function, whereas zinc removal restores its function as evidenced from high-speed AFM, electron microscopy, chromatography, and NMR results. These findings emphasize the catalytic role of cf-E111Q-IDE on Aβ degradation and urge the development of zinc chelators as an alternative therapeutic strategy that switches on/off IDE's function.
MeSH term(s)	Alzheimer Disease/metabolism ; Amino Acid Sequence ; Amyloid beta-Peptides/chemistry ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Peptides/ultrastructure ; Biocatalysis ; Chromatography, High Pressure Liquid ; Humans ; Insulysin/chemistry ; Insulysin/genetics ; Insulysin/metabolism ; Mass Spectrometry ; Microscopy, Electron, Transmission ; Molecular Dynamics Simulation ; Mutant Proteins/chemistry ; Mutant Proteins/genetics ; Mutant Proteins/metabolism ; Mutation, Missense ; Peptide Fragments/chemistry ; Peptide Fragments/metabolism ; Peptide Fragments/ultrastructure ; Protein Binding ; Proteolysis ; Substrate Specificity ; Zinc/chemistry ; Zinc/metabolism
Chemical Substances	Amyloid beta-Peptides ; Mutant Proteins ; Peptide Fragments ; amyloid beta-protein (1-40) ; Insulysin (EC 3.4.24.56) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2021-04-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2021.166993
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Zs.A 867: Show issues

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Article ; Online: Novel Radiographic Measurements for Operatively Treated Haglund's Deformity.

Tang, Shih-Chieh / Tu, Kao-Chang / Liao, Wei-Jen / Hsu, Chang-Te / Shih, Han-Ting / Tung, Kuan-Kai / Wu, Min-Huan / Wang, Shun-Ping

Tomography (Ann Arbor, Mich.)

2022 Volume 8, Issue 1, Page(s) 284–292

Abstract: Background: Haglund's deformity, which is characterized by a bony prominence of the posterosuperior aspect of the calcaneus, causes posterior heel pain. To date, there is no standard radiographic parameter to diagnose symptomatic Haglund's deformity. ... ...

Abstract	Background: Haglund's deformity, which is characterized by a bony prominence of the posterosuperior aspect of the calcaneus, causes posterior heel pain. To date, there is no standard radiographic parameter to diagnose symptomatic Haglund's deformity. Herein, we proposed novel radiographic measurements to distinguish between patients with and without symptomatic Haglund's deformity. Methods: We retrospectively evaluated ankle radiographs of 43 patients who underwent surgery for symptomatic Haglund's deformity (Haglund group) and 41 healthy individuals (control group) free of heel complaints. Fowler-Phillip angle (FPA), Heneghan-Pavlov parallel pitch lines (PPL), Haglund's deformity height, bump height, and bump-calcaneus ratio were measured and compared between the groups. Furthermore, the reliability and cut-off value of each parameter were validated via ICC and ROC curve analysis, respectively. Results: The bump height ( Conclusions: This study proposes two novel radiographic parameters to identify operatively treated Haglund's deformity, namely bump height and bump-calcaneus ratio. They are easy to measure and intuitive. Both of them are effective diagnostic parameters for Haglund's deformity. Furthermore, bump-calcaneus ratio is more reliable diagnostic parameter than bump height.
MeSH term(s)	Achilles Tendon/surgery ; Exostoses ; Heel Spur/diagnosis ; Humans ; Reproducibility of Results ; Retrospective Studies
Language	English
Publishing date	2022-02-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-139X
ISSN (online)	2379-139X
DOI	10.3390/tomography8010023
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Article ; Online: Catalytic Mechanism of Amyloid-β Peptide Degradation by Insulin Degrading Enzyme: Insights from Quantum Mechanics and Molecular Mechanics Style Møller-Plesset Second Order Perturbation Theory Calculation.

Lai, Rui / Tang, Wei-Jen / Li, Hui

Journal of chemical information and modeling

2018 Volume 58, Issue 9, Page(s) 1926–1934

Abstract: Insulin degrading enzyme (IDE), a metalloprotease that degrades amyloid-β (Aβ) peptides and insulin, is associated with Alzheimer's disease and diabetes. The mechanism of IDE catalyzed degrading of Aβ peptides, which is of fundamental importance in the ... ...

Abstract	Insulin degrading enzyme (IDE), a metalloprotease that degrades amyloid-β (Aβ) peptides and insulin, is associated with Alzheimer's disease and diabetes. The mechanism of IDE catalyzed degrading of Aβ peptides, which is of fundamental importance in the design of therapeutic methods for Alzheimer's disease, has not been fully understood. In this work, combined quantum mechanics and molecular mechanics (QM/MM) style Møller-Plesset second order perturbation theory (MP2) geometry optimization calculations are performed to investigate the catalytic mechanism of the Aβ40 Phe19-Phe20 peptide bond cleavage by human IDE. The analyses using QM/MM MP2 optimization suggest that a neutral water molecule is at the active site of the enzyme-substrate (ES) complex. The water molecule is in hydrogen bonding with the nearby anionic Glu111 of IDE but not directly bound to the catalytic Zn ion. This is confirmed by QM/MM DFTB3 molecular dynamics simulation. Our studies also reveal that the hydrolysis of the Aβ40 Phe19-Phe20 peptide bond by IDE consists of four key steps. The neutral water is first activated by moving toward and binding to the Zn ion. A gem-diol intermediate is then formed by the activated neutral water molecule attacking the C atom of the Phe19-Phe20 peptide bond. The next is the protonation of the N atom of Phe19-Phe20 peptide bond to form an intermediate with an elongated C-N bond. The final step is the breaking of the Phe19-Phe20 C-N bond. The final step is the rate-determining step with a calculated Gibbs free energy of activation of 17.34 kcal/mol, in good agreement with the experimental value 16.7 kcal/mol. This mechanism provides the basis for the design of biochemical methods to modulate the activity of IDE in humans.
MeSH term(s)	Amyloid beta-Peptides/chemistry ; Catalysis ; Insulysin/metabolism ; Kinetics ; Models, Molecular ; Protein Binding ; Protein Conformation ; Proteolysis ; Quantum Theory ; Software ; Water ; Zinc
Chemical Substances	Amyloid beta-Peptides ; Water (059QF0KO0R) ; Insulysin (EC 3.4.24.56) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2018-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	190019-5
ISSN	1549-960X ; 0095-2338
ISSN (online)	1549-960X
ISSN	0095-2338
DOI	10.1021/acs.jcim.8b00406
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Zs.A 1230: Show issues

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Article ; Online: Pseudomonas aeruginosa

Mancl, Jordan M / Suarez, Cristian / Liang, Wenguang G / Kovar, David R / Tang, Wei-Jen

The Journal of biological chemistry

2020 Volume 295, Issue 11, Page(s) 3506–3517

Abstract: Pseudomonas ... ...

Abstract	Pseudomonas aeruginosa
MeSH term(s)	Actin Cytoskeleton/metabolism ; Actin Cytoskeleton/ultrastructure ; Actin Depolymerizing Factors/metabolism ; Actins/chemistry ; Actins/metabolism ; Actins/ultrastructure ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bacterial Proteins/ultrastructure ; Glucosyltransferases/chemistry ; Glucosyltransferases/genetics ; Glucosyltransferases/metabolism ; Glucosyltransferases/ultrastructure ; Membrane Glycoproteins/metabolism ; Microfilament Proteins/metabolism ; Models, Molecular ; Mutation/genetics ; Protein Binding ; Protein Multimerization ; Pseudomonas aeruginosa/enzymology
Chemical Substances	Actin Depolymerizing Factors ; Actins ; Bacterial Proteins ; Membrane Glycoproteins ; Microfilament Proteins ; plastin ; ExoY protein, bacteria (EC 2.4.-) ; Glucosyltransferases (EC 2.4.1.-)
Language	English
Publishing date	2020-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA119.012320
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Article ; Online: Reinvestigating the synthesis and efficacy of small benzimidazole derivatives as presequence protease enhancers.

Li, Nan-Sheng / Liang, Wenguang / Piccirilli, Joseph A / Tang, Wei-Jen

European journal of medicinal chemistry

2019 Volume 184, Page(s) 111746

Abstract: Presequence protease (PreP) is a proteostatic enzyme that plays a key role in the maintenance of mitochondrial health. Defects in PreP stability are associated with neurological disorders in humans, and altered activity of this enzyme modulates the ... ...

Abstract	Presequence protease (PreP) is a proteostatic enzyme that plays a key role in the maintenance of mitochondrial health. Defects in PreP stability are associated with neurological disorders in humans, and altered activity of this enzyme modulates the progress of Alzheimer's disease-like pathology in mice. As agonists that boost PreP proteolytic activity represent a promising therapeutic avenue, we sought to determine the structural basis for the action of benzimidazole derivatives (3c and 4c), first reported by Vangavaragu et al. (Eur. J. Med. Chem. 76 (2014) 506-516) that enhance the activity of PreP. However, we found the published procedure for the synthesis of 3c yielded aldimine A instead. We then developed an alternative synthesis and obtained 3c, termed compound C, and an alternative benzimidazole derivative, termed compound B. We tested compounds A, B and C for their ability to enhance the activities of human PreP. In contrast to the previous report, we observed that none of the compounds A, B, or C (3c) modulated the catalytic activity of human PreP. Here we report our findings on the mis-identification of the reported benzimidazoles and the lack of biological activity of such compounds on human PreP. Thus, PreP modulators for PreP-based therapies remain to be discovered.
MeSH term(s)	Benzimidazoles/chemical synthesis ; Benzimidazoles/chemistry ; Benzimidazoles/pharmacology ; Dose-Response Relationship, Drug ; Humans ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/isolation & purification ; Mitochondrial Proteins/metabolism ; Molecular Structure ; Serine Endopeptidases/genetics ; Serine Endopeptidases/isolation & purification ; Serine Endopeptidases/metabolism ; Small Molecule Libraries/chemical synthesis ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; Structure-Activity Relationship
Chemical Substances	Benzimidazoles ; Mitochondrial Proteins ; Small Molecule Libraries ; benzimidazole (E24GX49LD8) ; PREP protein, human (EC 2.4.21.25) ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2019-10-01
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2019.111746
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