IKKε inhibitors(inhibitor of nuclear factor kappa B kinase subunit epsilon inhibitors), QIK subfamily inhibitors, TBK1 inhibitors(Serine/threonine-protein kinase TBK1 inhibitors)

+ [2]

Therapeutic Areas

NeoplasmsImmune System DiseasesOther Diseases

Active Indication-

Inactive Indication

Autoimmune DiseasesInflammationNeoplasms

Originator Organization

University Of Dundee

Active Organization-

Inactive Organization

University Of Dundee

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC26H36N6O2

InChIKeyUKBGBACORPRCGG-UHFFFAOYSA-N

CAS Registry1190378-57-4

100 Clinical Results associated with MRT67307

100 Translational Medicine associated with MRT67307

100 Patents (Medical) associated with MRT67307

Literatures (Medical) associated with MRT67307

01 May 2025·Veterinary Microbiology

Serum amyloid P component suppresses porcine epidemic diarrhea virus replication through TLR4-mediated IFN-β signaling pathway

Article

Author: Zhu, Huixin ; Xu, Yufan ; Liu, Mingyu ; Lu, Xinchang ; Wang, Xianwei ; Bai, Juan ; Jiang, Ping ; Yang, Zhen

Porcine epidemic diarrhea virus (PEDV) is a porcine enteropathogenic coronavirus that causes significant economic losses in many Asian and European countries. It is characterized by lethal watery diarrhea and high mortality rate in piglets. Serum amyloid P component (SAP), a member of acute response phase protein (APP) family, has been reported to play a crucial role in innate immune response against various microbial pathogens. However, its antiviral activities are little known. In this study, the antiviral activity of SAP during PEDV infection was investigated. In virus-infected IPEC cells, it was found that SAP expression was significantly upregulated. To study the role of SAP in PEDV replication, the expression of SAP was regulated in cells using eukaryotic expression plasmids expressing the SAP protein and sgRNA. PEDV replication was then assessed through real-time PCR, Western blotting, and TCID₅₀ assays. The result showed that PEDV replication was inhibited in cells overexpressing SAP and promoted in cells with SAP knocking out. To further investigate the mechanism by which SAP inhibits PEDV replication, Interferon Beta (IFN-β) and its related signaling pathway proteins were detected. The results demonstrated that SAP activates the promoter of (IFN-β) and IFN regulatory factor 3 (IRF3) mediated by Toll-Like Receptor 4 (TLR4) signaling. During PEDV infection, SAP enhances TLR4-mediated IFN-β signaling, leading to increased IFN-β expression, which subsequently suppresses PEDV replication. By using TBK1/IKBKE inhibitor MRT67307 in PEDV-infected cells, the antiviral activity of SAP was inhibited. This suggests that the antiviral effect of SAP may rely on the activation of the TBK1/IKBKE signaling pathway, which is critical for the induction of type I interferons and other antiviral responses. Moreover, the interaction between SAP and PEDV N protein and the functional domain of SAP were investigated. From the results of this study, it can be concluded that the interaction between SAP and PEDV N protein activates the TLR4-mediated IFN signaling pathway, thereby inhibiting PEDV replication.

01 Jan 2025·iScience

Heme regulates protein interactions and phosphorylation of BACH2 intrinsically disordered region in humoral response

Article

Author: Nakagawa, Tadashi ; Ikeda, Mariko ; Matsumoto, Mitsuyo ; Igarashi, Kazuhiko ; Kadoya, Shun ; Watanabe-Matsui, Miki ; Nagasawa, Yuko ; Ochiai, Kyoko ; Shirouzu, Mikako ; Hayashi, Shuichiro ; Segawa, Kei ; Doh-Ura, Katsumi ; Nakayama, Keiko ; Nguyen, Long C ; Shima, Hiroki ; Muto, Akihiko ; Murayama, Kazutaka

Heme is known to bind to the intrinsically disordered region (IDR) to regulate protein function. The binding of heme to the IDR of transcription factor BACH2 promotes plasma cell differentiation, but the molecular basis is unknown. Heme was found to increase BACH2 IDR interaction with TANK-binding kinase 1 (TBK1). TBK1 inactivated BACH2 by phosphorylation of its IDR, whereas BACH2 repressed TBK1 gene expression. BACH2 phosphorylation by TBK1 inhibited its interaction with the co-repressor NCOR1 and promoted plasma cell differentiation. Heme also induced BACH2 binding to ubiquitin E3 ligase adaptor FBXO22, which polyubiquitinated BACH2 only in the presence of heme in vitro. Mutations of some of the TBK1-mediated phosphorylation sites promoted BACH2-FBXO22 interaction, while additional mutations abrogated their interaction, suggesting that TBK1 can both inhibit and promote BACH2-FBXO22 interaction. Therefore, heme regulates phosphorylation of BACH2 IDR by TBK1 and its interaction with NCOR1 and FBXO22, leading to de-repression of BACH2 target genes in humoral immunity.

14 Oct 2024·Journal of Chemical Information and Modeling

In Silico Insights: QSAR Modeling of TBK1 Kinase Inhibitors for Enhanced Drug Discovery

Article

Author: Ivanov, Julian M. ; Iyer, Kavita A. ; Zhou, Qiongqiong Angela ; Agarwal, Shivangi ; Ralhan, Krittika ; Tenchov, Rumiana

TBK1, or TANK-binding kinase 1, is an enzyme that functions as a serine/threonine protein kinase. It plays a crucial role in various cellular processes, including the innate immune response to viruses, cell proliferation, apoptosis, autophagy, and antitumor immunity. Dysregulation of TBK1 activity can lead to autoimmune diseases, neurodegenerative disorders, and cancer. Due to its central role in these critical pathways, TBK1 is a significant focus of research for therapeutic drug development. In this paper, we explore data from the CAS Content Collection regarding TBK1 and its implication in a large assortment of diseases and disorders. With the demand for developing efficient TBK1 inhibitors being outlined, we focus on utilizing a machine learning approach for developing predictive models for TBK1 inhibition, derived from the fragment-functional analysis descriptors. Using the extensive CAS Content Collection, we assembled a training set of TBK1 inhibitors with experimentally measured IC50 values. We explored several machine learning techniques combined with various molecular descriptors to derive and select the best TBK1 inhibitor QSAR models. Certain significant structural alerts that potentially contribute to inhibition of TBK1 are outlined and discussed. The merit of the article stems from identifying the most adequate TBK1 QSAR models and subsequent successful development of advanced positive training data to facilitate and enhance drug discovery for an important therapeutic target such as TBK1 inhibitors, based on an extensive, wide-ranging set of scientific information provided by the CAS Content Collection.

100 Deals associated with MRT67307

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Autoimmune Diseases	Preclinical	United Kingdom	University Of Dundee	02 Oct 2012
Inflammation	Preclinical	United Kingdom	University Of Dundee	02 Oct 2012
Neoplasms	Preclinical	United Kingdom	University Of Dundee	27 Jan 2011

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

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


No Data

MRT67307

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation