Role of SCO-792, A Novel Enteropeptidase Inhibitor, In the Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis

Rashid, Mohammed Yousif; Noor, Asfa; Patel, Viral; Henin, Shereen; Cuello-Ramírez, Alejandrina; Kaabi, Anoud S Al; Gnawali, Anupa; Mostafa, Jihan A

doi:10.7759/cureus.13724

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…The reflux of EP into the gland could trigger the inappropriate activation of the stored zymogens, which may be associated with acute necrotizing pancreatitis ( 5 ). Additionally, endoscopic retrograde cholangiopancreatography (ERCP) will interject duodenal juice that rich in EP, into the pancreatic-biliary tract, which causes inappropriately activation of trypsinogen, thereby initiating acute pancreatitis ( 65 ). However, all the above studies are based on increasing EP in the intestinal or pancreatic-biliary tract and absence of clinical evidence that EP activates trypsinogen in situ in the pancreas.…”

Section: Discussionmentioning

confidence: 99%

The Global Status and Trends of Enteropeptidase: A Bibliometric Study

et al. 2022

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BackgroundEnteropeptidase (EP) is a type II transmembrane serine protease and a physiological activator of trypsinogen. Extensive studies related to EP have been conducted to date. However, no bibliometric analysis has systematically investigated this theme. Our study aimed to visualize the current landscape and frontier trends of scientific achievements on EP, provide an overview of the past 120 years and insights for researchers and clinicians to facilitate future collaborative research and clinical intervention.MethodsQuantitative analysis of publications relating to EP from 1900 to 2020 was interpreted and graphed through the Science Citation Index Expanded of Web of Science Core Collection (limited to SCIE). Microsoft office 2019, GraphPad Prism 8, VOSviewer, and R-bibliometrix were used to conduct the bibliometric analysis.ResultsFrom 1900 to 2020, a total of 1,034 publications were retrieved. The USA had the largest number of publications, making the greatest contribution to the topic (n = 260, 25.15%). Active collaborations between countries/regions were also enrolled. Grant and Hermontaylor were perhaps the most impactful researchers in the landscape of EP. Protein Expression and Purification and the Journal of Biological Chemistry were the most prevalent (79/1,034, 7.64%) and cited journals (n = 2,626), respectively. Using the top 15 citations and co-citations achievements clarified the theoretical basis of the EP research field. Important topics mainly include the structure of EP, the affective factors for activating substrates by EP, EP-related disorders, and inhibitors of EP.ConclusionBased on the bibliometric analysis, we have gained a comprehensive analysis of the global status and research frontiers of studies investigating EP, which provides some guidance and reference for researchers and clinicians engaged in EP research.

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Section: Discussionmentioning

confidence: 99%

The Global Status and Trends of Enteropeptidase: A Bibliometric Study

et al. 2022

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“…Furthermore, duodenopancreatic reflux of activated EP can trigger the pancreatic enzyme cascade, leading to acute necrotizing pancreatitis 2,[16][17][18][19] . Additionally, translocation of EP into the pancreatic-biliary tract has been shown to associated with pancreatitis 20 . Therefore, EP has attracted intense interests as a drug target 10,21,22 .…”

Section: Introductionmentioning

confidence: 99%

Cryo-EM structures reveal the activation and substrate recognition mechanism of human enteropeptidase

Huang

Yang

et al. 2022

Preprint

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The enteropeptidase (EP) initiates the intestinal digestion by proteolytic processing of trypsinogen, generating catalytic active trypsin. The dysfunction of EP will cause a series of pancreatic diseases, the most severe of which is acute necrotizing pancreatitis. However, the molecular mechanism of EP activation and substrate recognition remain elusive due to the lack of structural information, hampering the structure-based research of EP and even further EP-targeted drug design. Here we report cryo-EM structures of human EP in multiple states, covering the functional cycle spanning from inactive to active state and eventually to the substrate binding state, with the inactive core region reached an atomic resolution of 2.7 angstrom. The heavy chain of EP exhibits a clamping configuration with the CUB2 domain serving for substrate recognition. The N-terminus of light chain induces the surface loop remodeling from inactive to active conformation, resulting in a highly dynamic and active EP. Then the heavy chain performs like a hinge to ensure the flexibility of light chain for substrate recruitment and subsequent cleavage. Our study provides structural insights of EP remodeling and heavy chain dynamics while performing enzymatic function, facilitating our understanding of the pathogenies of EP-related pancreatitis and the EP-targeted treatment of pancreatitis.

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“…Enteropeptidase inhibition may prevent and lessen the severity of postendoscopic retrograde cholangiopancreatography pancreatitis because enterokinase plays a crucial role in the pathophysiology of pancreatitis. 13 There have only been 13 cases of enterokinase insufficiency recorded since it was originally characterized in 1969. Vomiting, diarrhoea, hypoproteinemia, and failure to thrive were among the persistent symptoms.…”

Section: Introductionmentioning

confidence: 99%

Intestinal Enterokinase Deficiency in Pediatrics

Fadl¹,

Alabdullatif²,

S³

et al. 2022

Int J Life Sci Pharm Res

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Congenital enteropeptidase deficiency (CEP), also known as enterokinase deficiency. CEP is an uncommon autosomal recessive genetic disorder mostly characterized by severe chronic diarrhoea after delivery, hypoproteinemia, and failure to grow. Enteropeptidase activity is anticipated to play a significant role in protein digestion. For growth and appropriate development in newborns with a congenital lack of the enzyme, pancreatic enzyme replacement treatment or an amino acid combination must be given. Only 13 cases of enterokinase insufficiency have been recorded since it was originally characterized in 1969. Couples should be informed that prenatal screening is an option and that EKD has a favourable prognosis. However, if an EKD patient is born, parents should be aware of the feeding issue and offer the proper pancreatic exocrine secretion medication. One research found that all patients had been diagnosed as newborns 25 years ago. Even when the pancreatic-enzyme replacement was stopped, they appeared to lead regular lives as adults, free of gastrointestinal issues and with normal body weight. This can be explained by the fact that trypsin, once liberated from its precursor, encourages additional trypsinogen activation in a positive-feedback manner. Better pharmaceutical preparations such as enteric-coated minimicrospheres and delayed-release capsules are used for better results as it maintains the enzyme and prevents its breakdown by stomach acidity. This review aims to summarise current knowledge of pathophysiology, causes, and treatment of Intestinal Enterokinase Deficiency in Pediatrics

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Role of SCO-792, A Novel Enteropeptidase Inhibitor, In the Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis

Cited by 4 publications

References 31 publications

The Global Status and Trends of Enteropeptidase: A Bibliometric Study

The Global Status and Trends of Enteropeptidase: A Bibliometric Study

Cryo-EM structures reveal the activation and substrate recognition mechanism of human enteropeptidase

Intestinal Enterokinase Deficiency in Pediatrics

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