A high-throughput screening assay for dipeptidyl peptidase-IV inhibitors using human plasma

2021 ◽  
Author(s):  
Liwei Zou ◽  
Jing Zhang ◽  
Xingkai Qian ◽  
Peifang Song ◽  
Xiaodong Li ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Fluorescence Probe ◽  
Critical Role ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Screening Assay ◽  
Dpp Iv ◽  
High Throughput Screening Assay ◽  
Dipeptidyl Peptidase Iv Inhibitors ◽  
Two Photon Fluorescence

Dipeptidyl peptidase-IV (DPP-IV) plays a critical role in glucose metabolism and has become an important target for type 2 diabetes mellitus. We previously reported a two-photon fluorescence probe glycyl-prolyl-N-butyl-4-amino-1,8-naphthalimide (GP-BAN)...

Dipeptidyl Peptidase IV Inhibitors for Nonalcoholic Fatty Liver Disease – Systematic Review and Metanalysis

2020 ◽  
Vol 16 ◽  
Author(s):  
Lucas Ribeiro dos Santos ◽  
Marcio Luis Duarte ◽  
Maria Stella Peccin ◽  
Antônio Ricardo de Toledo Gagliardi ◽  
Tamara Melnik
Keyword(s):  
Hepatic Steatosis ◽  
Grey Literature ◽  
Specific Treatment ◽  
Reducing Power ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Cochrane Library ◽  
Vast Number ◽  
Dpp Iv ◽  
Dipeptidyl Peptidase Iv Inhibitors

Introduction:: Hepatic steatosis is a frequent condition, that afflicts, especially, obese and insulin resistant patients; diagnosis is made, usually, through imaging tests. Despite the high prevalence and risk of complications, there is no specific treatment approved, though a vast number of medications have been tested. Objective:: To determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP-IV) in the treatment of NAFLD. Methods:: We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE and LILACS, as well as reference lists of the included studies and grey literature; 9 studies were selected for inclusion. Results:: 7 studies were used for metanalysis, for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83 [95% CI 35.23 to 13.57] at 3 months and MD -9.27 [95% CI 10.92 to -7.62] at 6 months of intervention, as well as reduction of hepatic steatosis via MRI of SMD 0.10 [95% CI 0.31 to 0.50]; the overall incidence of adverse events was very low. The studies were considered of low and very low quality by the GRADE evaluation. Conclusion:: Because of the poor overall quality of the studies and heterogeneity of the population analyzed, i DPP-IV did not show efficacy on inflammatory markers or fibrosis in patients with NAFLD.

Critical Role of Dipeptidyl Peptidase IV: A Therapeutic Target for Diabetes and Cancer

2018 ◽  
Vol 19 (2) ◽  
pp. 88-97 ◽  
Author(s):  
Sourav De ◽  
Subhasis Banerjee ◽  
S.K. Ashok Kumar ◽  
Priyankar Paira
Keyword(s):  
Drug Targets ◽  
Critical Role ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dpp Iv ◽  
Protease Enzyme ◽  
Target Disease ◽  
Dimeric Form ◽  
Epithelium Cells

Diabetes mellitus is an emerging predator and affecting around 422 million adults worldwide. Higher levels of circulating insulin and increased pressure on the pancreas to produce insulin have been inferred as possible etiology for diabetes leading to a higher risk of pancreatic cancer. Out of several drug targets in hypoglycemic discovery, Dipeptidyl peptidase-IV (DPP-IV) has been considered an emerging target. It is a protease enzyme which inactivates incretin hormones i.e., Glucagonlike peptide 1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP). Inhibition of DPP-4 results in the longer action of GLP-1 and GIP, therefore, DPP-4 inhibitors play an important role in maintaining glucose homeostasis. In comparison to early oral hypoglycemic, DPP-IV inhibitors are well tolerated and provide a better glycemic control over a longer period. These enzymes are expressed in a dimeric form on the surface of different cells such as prostate, liver and small intestinal epithelium cells. Disruption of the local signaling environment is an emerging factor in cancer development. Till date, not even a single DPP-IV inhibitor as anticancer has been developed. This review focuses on various features of the enzyme and their suitable inhibitors for target disease.

scholarly journals Development of High-Throughput Screening Assay for Antihantaviral Therapeutics

2017 ◽  
Vol 22 (6) ◽  
pp. 767-774
Author(s):  
Anuradha Roy ◽  
Mohammad A. Mir
Keyword(s):  
High Throughput ◽  
Therapeutic Intervention ◽  
Nucleocapsid Protein ◽  
High Throughput Screening ◽  
Critical Role ◽  
Hantavirus Infection ◽  
Screening Assay ◽  
Chemical Libraries ◽  
Conserved Sequence ◽  
High Throughput Screening Assay

Humans acquire hantavirus infection by the inhalation of aerosolized excreta of infected rodent hosts. There is no treatment for hantavirus diseases at present. Therapeutic intervention during early stages of viral infection can improve the outcome of this zoonotic viral illness. The interaction between an evolutionary conserved sequence at the 5′ terminus of hantaviral genomic RNA and hantavirus nucleocapsid protein plays a critical role in the hantavirus replication cycle. This unique interaction is a novel target for therapeutic intervention of hantavirus disease. We developed a very sensitive, tractable, and cost-effective fluorescence-based assay to monitor the interaction between the nucleocapsid protein and the target RNA sequence. The assay was optimized for high-throughput screening of chemical libraries to identify molecules that interrupt this RNA–protein interaction. The assay was validated using a library of 6880 chemical compounds. This validation screen demonstrated the reproducibility and validity of required statistical criteria for high-throughput screening. The assay is ready to use for high-throughput screening of large chemical libraries to identify antihantaviral therapeutic molecules and can be amenable to similar targets in other viruses.

scholarly journals Streptokinase Promotes Development of Dipeptidyl Peptidase IV (CD26) Autoantibodies after Fibrinolytic Therapy in Myocardial Infarction Patients

2002 ◽  
Vol 9 (6) ◽  
pp. 1253-1259 ◽  
Author(s):  
Miguel Cuchacovich ◽  
Héctor Gatica ◽  
Paula Vial ◽  
Jorge Yovanovich ◽  
Salvatore V. Pizzo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Lupus Erythematosus ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Serum Levels ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Necrosis Factor Alpha ◽  
Dpp Iv ◽  
Tnf Α

ABSTRACT Dipeptidyl peptidase IV (DPP IV) (CD26) plays a critical role in the modulation and expression of autoimmune and inflammatory diseases. We recently reported that sera from patients with rheumatoid arthritis and systemic lupus erythematosus contained low levels of DPP IV and high titers of anti-DPP IV autoantibodies of the immunoglobulin A (IgA) and IgG classes and found a correlation between the low circulating levels of DPP IV and the high titers of anti-DPP IV autoantibodies of the IgA class. Since streptokinase (SK) is a potent immunogen and binds to DPP IV, we speculated that patients with autoimmune diseases showed higher DPP IV autoantibody levels than healthy controls as a consequence of an abnormal immune stimulation triggered by SK released during streptococcal infections. We assessed this hypothesis in a group of patients suffering from acute myocardial infarction, without a chronic autoimmune disease, who received SK as part of therapeutic thrombolysis. Concomitant with the appearance of anti-SK antibodies, these patients developed anti-DPP IV autoantibodies. These autoantibodies bind to DPP IV in the region which is also recognized by SK, suggesting that an SK-induced immune response is responsible for the appearance of DPP IV autoantibodies. Furthermore, we determined a correlation between high titers of DPP IV autoantibodies and an augmented clearance of the enzyme from the circulation. Serum levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) increased significantly after 30 days of SK administration, while the levels of soluble IL-2 receptor remained unchanged during the same period, suggesting a correlation between the lower levels of circulating DPP IV and higher levels of TNF-α and IL-6 in serum in these patients.

Sign in / Sign up

Export Citation Format

Share Document