Delving into the Latest Updates on Netazepide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CCKB

Action

antagonists

Mechanism

CCKB antagonists(Cholecystokinin B receptor antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Barrett EsophagusZollinger-Ellison Syndrome

Inactive Indication

Barretts esophagus with high grade dysplasiaCarcinoid TumorDyspepsia+ [5]

Originator Organization

Ferring BV

Active Organization

Ferring BV

Inactive Organization

Trio Medicines Ltd.

Ferring Pharmaceuticals A/S

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC28H30N6O3

InChIKeyYDZYKNJZCVIKPP-VWLOTQADSA-N

CAS Registry155488-25-8

BACKGROUNDAmong bariatric techniques, sleeve gastrectomy (SG) stands out owing to its efficiency. The role of the stomach as a secretory organ of many substances, such as gastrin, related to insulin secretion is well known. Gastrin induces insulin release in isolated pancreatic islets, limiting somatostatin-14 intraislet release, and has been associated with blood glucose level improvement in diabetic models after SG. SG involves gastric resection along the greater curvature. This study aimed to determine the role of gastrin in glucose metabolism improvement after SG with the aid of the gastrin antagonist netazepide.METHODSIn 12 sham-operated, 12 SG-operated, and 12 SG-operated/netazepide-treated Wistar rats, we compared medium- and long-term plasma insulin, oral glucose tolerance test (OGTT) results, and plasma gastrin levels. In addition, gastrin expression was assessed in the gastric remnant, and the beta-cell mass was measured.RESULTSSG induced a medium-term elevation of the insulin response and plasma gastrin levels without modification of the OGTT results. However, long-term depletion of the insulin response with elevated OGTT areas under the curve and plasma gastrin levels appeared after SG. Netazepide prevented the SG effect on these parameters. Gastrin tissue expression was greater in SG animals than in SG/netazepide-treated or control animals. The beta-cell mass was lower in the SG group than in the control or SG/netazepide group.CONCLUSIONGastrin plays a central role in glucose improvement after SG. It stimulates a medium-term strong insulin response but also causes long-term beta-cell mass depletion and a loss of insulin response. These effects are prevented by gastrin antagonists such as netazepide.

01 Oct 2023·Molecular Diversity

Identification of small molecules as potential inhibitors of interleukin 6: a multi-computational investigation

Article

Author: Thai, Khac-Minh ; Le, Minh-Tri ; Nguyen, Quoc-Thai ; Tran, Viet-Hung ; Tran, Que-Huong ; Trinh, Dieu-Thuong Thi ; Tran, Thanh-Dao ; Tran, Van-Thanh ; Tran, Thi-Thuy Nga

IL(interleukin)-6 is a multifunctional cytokine crucial for immunological, hematopoiesis, inflammation, and bone metabolism. Strikingly, IL-6 has been shown to significantly contribute to the initiation of cytokine storm-an acute systemic inflammatory syndrome in Covid-19 patients. Recent study has showed that blocking the IL-6 signaling pathway with an anti-IL-6 receptor monoclonal antibody (mAb) can reduce the severity of COVID-19 symptoms and enhance patient survival. However, the mAb has several drawbacks, such as high cost, potential immunogenicity, and invasive administration due to the large-molecule protein product. Instead, these issues could be mitigated using small molecule IL-6 inhibitors, but none are currently available. This study aimed to discover IL-6 inhibitors based on the PPI with a novel camelid Fab fragment, namely 68F2, in a crystal protein complex structure (PDB ID: 4ZS7). The pharmacophore models and molecular docking were used to screen compounds from DrugBank databases. The oral bioavailability of the top 24 ligands from the screening was predicted by the SwissAMDE tool. Subsequently, the selected molecules from docking and MD simulation illustrated a promising binding affinity in the formation of stable complexes at the active binding pocket of IL-6. Binding energies using the MM-PBSA technique were applied to the top 4 hit compounds. The result indicated that DB08402 and DB12903 could form strong interactions and build stable protein-ligand complexes with IL-6. These potential compounds may serve as a basis for further developing small molecule IL-6 inhibitors in the future.

26 Sep 2021·World Journal of Clinical CasesQ4 · MEDICINE

Gastric neuroendocrine neoplasms: A review

Q4 · MEDICINE

Review

Author: Sezikli, Mesut ; Köseoğlu, Hüseyin ; Duzenli, Tolga

Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.

100 Deals associated with Netazepide

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12355

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Barrett Esophagus	Phase 2	-	Ferring BV	-
Zollinger-Ellison Syndrome	Phase 2	-	Ferring BV	-
Carcinoid Tumor	Phase 1	United Kingdom	Trio Medicines Ltd.	04 Jan 2011
Gastritis, Atrophic	Phase 1	United Kingdom	Trio Medicines Ltd.	04 Jan 2011
Increased gastrin secretion	Phase 1	United Kingdom	Trio Medicines Ltd.	04 Jan 2011
Barretts esophagus with high grade dysplasia	Phase 1	United Kingdom	Trio Medicines Ltd.	01 Jun 2010
Barretts esophagus with high grade dysplasia	Phase 1	United States	Trio Medicines Ltd.	01 Jun 2010
Carcinoid Tumor	Discovery	United Kingdom	Trio Medicines Ltd.	04 Jan 2011
Gastritis, Atrophic	Discovery	United Kingdom	Trio Medicines Ltd.	04 Jan 2011
Increased gastrin secretion	Discovery	United Kingdom	Trio Medicines Ltd.	04 Jan 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01298999 (CTgov)	Phase 2	Barrett Esophagus \| Barretts esophagus with high grade dysplasia	27	YF476 (YF476)	toplyuzffh(ywgfczbwgh) = kyvrvsqxrv mkmwyifmyv (aczirkwjpa, ycfwhxirkv - tswnfvczko) View more	-	23 Nov 2021
				Placebo (Placebo)	toplyuzffh(ywgfczbwgh) = xgxomqtisu mkmwyifmyv (aczirkwjpa, oiqfuouhbf - firtmincag) View more
NCT02597712 (CTgov)	Phase 2	Barrett Esophagus	27	YF476 (Treatment)	tnigkfsmjf(nkugfrtqla) = vnerxrennl djsokpqxsc (hbtganbctf, gaxbpkkoyl - skzybbokfz) View more	-	12 Apr 2021
				YF476 placebo (YF476 Placebo)	tnigkfsmjf(nkugfrtqla) = rnotmxzxwg djsokpqxsc (hbtganbctf, rxdfelkevw - wdxuhssaum) View more
NCT01298999 (Pubmed \| Cancer Prev Res (Phila))	Phase 2	Barrett Esophagus	20	Netazepide	suxhvnuilz(pietxwqoct) = eaawlriajq gzykrxwptw (nkspcqhgey, 620.7)	-	29 Mar 2021
				Placebo	suxhvnuilz(pietxwqoct) = dnkekakqiw gzykrxwptw (nkspcqhgey, 640.3)
NCT02454075 (CTgov)	Phase 2	Zollinger-Ellison Syndrome \| Gastric Neuroendocrine Tumor G1	3	YF476	ivtztrndyo(wjngtvzyyc) = bxgndwgvxa uukcobnyej (ovmmrjqtvn, msjptcobxi - jkpejulvbf) View more	-	29 Jan 2021