TNF-α x NK1R

Last update 08 May 2025

Basic Info

Related Targets

TNF-αNK1R

Drugs associated with TNF-α x NK1R

KY-21

Target

NK1R x TNF-α

Mechanism

NK1R antagonists [+1]

Active Org.

OLYS Pharma Srl

Originator Org.

OLYS Pharma Srl

Active Indication

Pain

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TNF-α x NK1R

100 Translational Medicine associated with TNF-α x NK1R

0 Patents (Medical) associated with TNF-α x NK1R

273

Literatures (Medical) associated with TNF-α x NK1R

10 Mar 2025·Investigative Ophthalmology & Visual Science

Reversal of Diabetic Dry Eye by Topical Opioid Receptor Blockade Follows Dual Pathways

Article

Author: Sassani, Joseph W. ; Diaz, David ; Zagon, Ian S. ; McLaughlin, Patricia J.

PurposeTo determine pathways in the trigeminal ganglion and corneal epithelium that are targeted by topical naltrexone (NTX) treatment for dry eye.MethodsNTX drops were administered topically daily for 15 days to the corneal surface of male and female adult type 1 diabetic rats. Schirmer scores and corneal sensitivity were measured at baseline, 5, 10, and 15 days. Trigeminal ganglion and corneal epithelium were processed for immunohistochemistry to detect expression of opioid growth factor receptor (OGFr), Ki67, nerve growth factor, insulin-like growth factor-1, calcitonin gene-related peptide, substance P, and TNF-α. A proteomic study determined protein changes in the cornea.ResultsCorneal sensitivity and tear production in diabetic rats were restored to normal levels within 5 days after topical NTX. Assessment of corneal tissue after 15 days of treatment revealed that defects in OGFr expression, epithelial cell number, and Ki67+ expression were restored to normal by NTX. Inflammation markers (e.g., TNF-α) were reduced in tissue from diabetic rats treated with NTX. Proteomic data suggest diabetes causes dysregulation in inflammatory biological processes. The percentages of calcitonin gene-related peptide-positive neurons, but not substance P-positive neurons, in the trigeminal ganglion were increased after NTX treatment. Diabetic male and female rats responded to NTX in a comparable manner.ConclusionsType 1 diabetes results in decreased tear production and altered corneal surface sensitivity. These complications coincide with dysregulated OGFr that maintains ocular homeostasis. Reversal of dry eye and restoration of corneal sensitivity in diabetic male and female rats after 15 days of topical treatment with NTX occur following dual pathways of increased cellular proliferation and reduction of inflammation.

01 Feb 2025·Neuromodulation: Technology at the Neural Interface

Effects of Auricular Stimulation on Inflammatory Parameters: Results of a Systematic Review and Meta-Analysis of Randomized Controlled Trials

Review

Author: Dietzel, Joanna ; Cummings, Mike ; Scheibenbogen, Carmen ; Usichenko, Taras ; Willich, Stefan N ; Brinkhaus, Benno ; Hua, Kevin ; Bernatik, Miriam

BACKGROUNDThe number of randomized controlled trials (RCTs) using auricular stimulation (AS) techniques, such as transauricular vagus nerve stimulation, auricular electrostimulation, auricular acupuncture, and acupressure in experimental and clinical settings has increased markedly over the last three decades. This systematic review evaluates the effects of AS on biomarkers of inflammation and stress responses.MATERIALS AND METHODSThe following data bases were searched: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and Scopus Data base. Data collection and analysis were conducted independently by two reviewers. Quality and risk assessments of the included studies were performed, and a meta-analysis of the effects of the most frequently assessed biomarkers was conducted using RevMan statistical software.RESULTSA total of 1122 patients and healthy volunteers from 27 RCTs were included in this systematic review; 81% of the participants were female, with a median age of 51 years. Pooled data of 18 studies showed a significant effect of AS regarding a reduction of serum C-reactive protein, tumor necrosis factor-α, interleukin (IL)-6, and IL-10. Although IL-4, IL1β, cortisol, substance P and calcitonin gene-related peptide, and adrenocorticotropic hormone did not show any changes, salivary amylase increased under AS.CONCLUSIONSThe influence of inflammatory cytokines seems to be mediated by AS. More research is needed to investigate the effects of AS on the immunologic system in addition to its clinical significance in high-quality RCT.

01 Feb 2025·Journal of Biochemical and Molecular Toxicology

NK1R Antagonist, CP‐99,994 Ameliorates Dry Eye Disease via Inhibiting the Plk1‐Cdc25c‐Cdk1 Axis

Article

Author: Zou, Yuhao ; Gong, Bo ; Zhang, Ruifan ; Li, Huan ; Liu, Yi ; Li, Dongfeng ; Yu, Man

ABSTRACTSubstance P/high‐affinity neurokinin‐1 receptor (SP/NK1R) system plays a crucial role in the pathogenesis of dry eye disease (DED). NK1R antagonist can improve DED, but the mechanism of NK1R antagonist treating DED remains unclear. We examined the role of NK1R antagonist, CP‐99,994 in DED model by possessing the phenol red cotton thread test, corneal fluorescein staining, and hematoxylin and eosin staining. Enzyme linked immunosorbent assay was performed to determine the concentration of inflammatory factors. Additionally, RNA sequencing, enrichment analysis and protein‐protein interaction network were employed to identify the key targets. Real‐time quantitative PCR and western blot analysis were utilized to determine the expression of hub genes. Plk1 inhibitor, GSK461364 was applied to explore the treatment mechanism of CP‐99,994. The NK1R antagonist CP‐99,994 alleviated dry eye symptoms and the concentrations of IL‐6, IL‐1β, and TNF‐α were significantly decreased after CP‐99,994 treatment. We obtained 68 differentially expressed genes after CP‐99,994 treatment by RNA sequencing and pyroptosis‐related genes (Plk1, Cdc25c, Cdk1) were identified from protein‐protein interaction network as key targets of CP‐99,994 treating DED. The expression levels of the Plk1, Cdc25c, and Cdk1 were significantly upregulated in the DED group, and CP‐99,994 downregulated the expression of Plk1, Cdc25c, and Cdk1. Moreover, Plk1 inhibitor considerably promoted the therapeutic effect of CP‐99,994 on DED model by reducing the release of IL‐6, IL‐1β, and TNF‐α. The NK1R antagonist, CP‐99,994 mitigated DED symptoms via inhibiting Plk1‐Cdc25c‐Cdk1 axis, which served as a novel therapeutic target for DED treatment.

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