A Phase IIa, Proof of Concept Study to Evaluate the Reduction in Inflammatory Biomarkers and Assess Airway Function Following Administration of IMD-1041 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

COPD is a lung disease in which the lung is damaged, making it hard to breathe. In COPD, the airways/tubes that carry air in and out of the lungs are partly obstructed, making it difficult to get air in and out. COPD gets gradually worse over time. At the moment there is no cure for COPD. The best way to slow the disease is to stop smoking. Current medications are used to alleviate shortness of breath and cough, and to treat infections of the lungs that can worsen COPD.
Institute of Medicinal Molecular Design, Inc. (IMMD), a Japanese Drug Discovery Company is developing a compound code named IMD-1041. IMD-1041 is an investigational drug, meaning it is not yet on the market. It is an IKKb inhibitor developed for the treatment of COPD. Unlike most other medications used for COPD currently, IMD-1041 is in capsule form and needs to be taken twice a day. It is also unlike all other drugs in use because it treats the underlying cause of the symptoms.
The purpose of this study is to see if IMD-1041 has the ability to reduce inflammatory derived symptoms and airway remodelling (changes) by looking at certain changes in chemical levels in the blood and sputum (phlegm).

Start Date01 Jul 2008

Sponsor / Collaborator

IMMD, Inc.

EUCTR2008-001889-81-GB / Not yet recruitingNot Applicable

A Phase IIa, Proof of Concept Study to Evaluate the Reduction in Inflammatory Biomarkers and Assess Airway Function Following Administration of IMD-1041 in Patients with Chronic Obstructive Pulmonary Disease (COPD)

Start Date24 Jun 2008

Sponsor / Collaborator

IMMD, Inc.

EUCTR2007-000190-28-GB / Not yet recruitingNot Applicable

A Single Centre, Double-blind, Randomised Study To Investigate a Single Oral Dose of IMD-1041 in A Nasal Allergen Challenge (NAC) Model

Start Date22 Mar 2007

Sponsor / Collaborator

IMMD, Inc.

100 Clinical Results associated with IKKβ x NFKB1

100 Translational Medicine associated with IKKβ x NFKB1

0 Patents (Medical) associated with IKKβ x NFKB1

366

Literatures (Medical) associated with IKKβ x NFKB1

01 Jul 2024·Experimental and Clinical Endocrinology & Diabetes

Protective Role of MerTK in Diabetic Peripheral Neuropathy via Inhibition of the NF-κB Signaling Pathway

Article

Author: Mao, Fugang ; Yang, Qiuping ; Zhao, Yan ; Lan, Danfeng ; Fu, Yidan ; Wu, Bian ; Chen, Wenting ; Su, Xiaoyang

Abstract Introduction Diabetic peripheral neuropathy (DPN) impacts patient quality of life. In such patients, increased expression of mer tyrosine kinase (MerTK) has been demonstrated; however, its mechanism of action remains unclear. In this study, type 2 diabetes mellitus (T2DM) and DPN models were established in Sprague Dawley rats via low-dose streptozotocin and a high-fat diet and the mode of action of MerTK was examined. Methods MerTK-specific inhibitors were administered by gavage once daily for 2 weeks. Sciatic nerve conduction velocity and nerve structure were measured. The levels of MerTK, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and relevant biochemical indexes were detected. Results The study revealed upregulation of MerTK expression in T2DM and more so in DPN groups. Inhibiting MerTK led to reduced nerve conduction velocity and further deterioration of sciatic nerve structure, as evidenced by structural morphology. Concurrently, serum levels of total cholesterol, glycated hemoglobin, and triglyceride significantly increased. Moreover, levels of NF-κB increased in both serum and nerve tissue, alongside a significant rise in TNF-α and IL-1β expressions. MerTK could bind to the inhibitor of kappa B kinase beta (Ikbkb) in Schwann cells, establishing Ikbkb as a precursor to NF-κB activation. Discussion Inhibition of MerTK exacerbates neuropathy, indicating its protective role in DPN by suppressing the NF-κB pathway, highlighting a potential new target for its diagnosis and treatment.

01 May 2024·FEBS Open Bio

N6‐isopentenyladenosine inhibits aerobic glycolysis in glioblastoma cells by targeting PKM2 expression and activity

Article

Author: Savarese, Beatrice ; Piemonte, Erica ; Coppola, Laura ; Torelli, Giovanni ; Bifulco, Maurizio ; Galgani, Mario ; Bruzzaniti, Sara ; Laezza, Chiara ; Pagano, Cristina ; Avilia, Giorgio ; Navarra, Giovanna

Glioblastoma (GBM) is a primary tumor in the central nervous system with poor prognosis. It exhibits elevated glucose uptake and lactate production. This metabolic state of aerobic glycolysis is known as the Warburg effect. N6‐isopentenyladenosine (iPA), a natural cytokine modified with an isopentenyl moiety derived from the mevalonate pathway, has well‐established anti‐tumor activity. It inhibits cell proliferation in glioma cells, inducing cell death by apoptosis and/or necroptosis. In the present study, we found that iPA inhibits aerobic glycolysis in unmodified U87MG cells and in the same cell line engineered to over‐express wild‐type epidermal growth factor receptor (EGFR) or EGFR variant III (vIII), as well as in a primary GBM4 patient‐derived cell line. The detection of glycolysis showed that iPA treatment suppressed ATP and lactate production. We also evaluated the response of iPA treatment in normal human astrocyte primary cells, healthy counterpart cells of the brain. Aerobic glycolysis in treated normal human astrocyte cells did not show significant changes compared to GBM cells. To determine the mechanism of iPA action on aerobic glycolysis, we investigated the expression of certain enzymes involved in this metabolic pathway. We observed that iPA reduced the expression of pyruvate kinase M2 (PKM2), which plays a key role in the regulation of aerobic glycolysis, promoting tumor cell proliferation. The reduction of PKM2 expression is a result of the inhibition of the inhibitor of nuclear factor kappa‐B kinase subunit, beta/nuclear factor‐kappa B pathway upon iPA treatment. In conclusion, these experimental results show that iPA may inhibit aerobic glycolysis of GBM in stabilized cell lines and primary GBM cells by targeting the expression and activity of PKM2.

09 Jan 2024·Current Computer-Aided Drug Design

Exploration of Pharmacological Mechanisms of Dapagliflozin against Type 2 Diabetes Mellitus through PI3K-Akt Signaling Pathway based on Network Pharmacology Analysis and Deep Learning Technology

Article

Author: Chen, Yufan ; Liu, Junru ; Li, Xingxing ; Zhang, Fen ; Liu, Xizhi ; Dong, Yang ; Wu, Jie ; Hu, Guoliang ; Shi, Shuai

Background::Dapagliflozin is commonly used to treat type 2 diabetes mellitus (T2DM). However, research into the specific anti-T2DM mechanisms of dapagliflozin remains scarce.Objective::This study aimed to explore the underlying mechanisms of dapagliflozin against T2DM.Methods::Dapagliflozin-associated targets were acquired from CTD, SwissTargetPrediction, and SuperPred. T2DM-associated targets were obtained from GeneCards and DigSee. VennDiagram was used to obtain the overlapping targets of dapagliflozin and T2DM. GO and KEGG analyses were performed using clusterProfiler. A PPI network was built by STRING database and Cytoscape, and the top 30 targets were screened using the degree, maximal clique centrality (MCC), and edge percolated component (EPC) algorithms of CytoHubba. The top 30 targets screened by the three algorithms were intersected with the core pathway-related targets to obtain the key targets. DeepPurpose was used to evaluate the binding affinity of dapagliflozin with the key targets.Results::In total, 155 overlapping targets of dapagliflozin and T2DM were obtained. GO and KEGG analyses revealed that the targets were primarily enriched in response to peptide, membrane microdomain, protein serine/threonine/tyrosine kinase activity, PI3K-Akt signaling pathway, MAPK signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. AKT1, PIK3CA, NOS3, EGFR, MAPK1, MAPK3, HSP90AA1, MTOR, RELA, NFKB1, IKBKB, ITGB1, and TP53 were the key targets, mainly related to oxidative stress, endothelial function, and autophagy. Through the DeepPurpose algorithm, AKT1, HSP90AA1, RELA, ITGB1, and TP53 were identified as the top 5 anti-targets of dapagliflozin.Conclusion::Dapagliflozin might treat T2DM mainly by targeting AKT1, HSP90AA1, RELA, ITGB1, and TP53 through PI3K-Akt signaling.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis