Hyperoxia-induced acute lung injury (HALI) is a serious pulmonary disease, and its therapeutic effect is greatly limited by disordered oxidative stress microenvironment. Safe and efficient antioxidant-immunomodulatory therapy may be a promising strategy to maintain redox homeostasis in HALI. Herein, a novel therapeutic strategy (PCT) composed size-dependent melanin-like polydopamine nanocapsules (PC) and IKK-2 inhibitor TPCA-1 is developed to alleviate HALI. By flexibly tuning the size of nanocapsules, the lung-to-liver ratio could be finely optimized, which facilitates to delivery adequate dose of TPCA-1 to pulmonary lesions and improve the bioavailability. Notably, these nanocapsules exhibit superior biosafety in vitro and in vivo. The selected PCT sharply scavenges intracellular reactive oxygen species (ROS) and protects mitochondrial function, subsequently reprogramming the repolarization of macrophages. Moreover, injection of PCT eliminates elevated ROS and oxidative stress products against the redox imbalance in HALI mice. Mechanistically, benefiting from much ROS depletion, PCT plays a positive role in inhibiting immune cell infiltration, down-regulating multiple inflammatory factors, and promoting macrophage polarization toward anti-inflammatory M2 phenotype through activating the Keap-1/Nrf2 pathway, thus remarkably breaking the vicious cycle of inflammation and oxidative stress in HALI. Overall, these findings provide a secure and effective therapy combining antioxidation and immunoregulation for HALI and other pulmonary diseases.

01 Mar 2025·Journal of Biotechnology

Interferon inhibitors increase rAAV production in HEK293 cells

Article

Author: Yoon, Seongkyu ; Fu, Qiang ; Sha, Sha ; Wang, Yongdan

Recombinant adeno-associated viruses (rAAVs) comprise a promising viral vector for therapeutic gene delivery to treat disease. However, the current manufacturing capability of rAAVs must be improved to meet commercial demand. Previously published omics studies indicate that rAAV production through transient transfection triggers antiviral responses and endoplasmic reticulum stress responses in the host cell. Both responses negatively regulate viral production. We demonstrate that the modulation of the antiviral immune response (by blocking interferon signaling pathways) can effectively lower the production of interferon and enhance viral genome production. The use of interferon inhibitors before transfection can significantly increase rAAV production in HEK293 cells, with up to a 2-fold increase in productivity and up to a 6-fold increase in specific productivity. Compared to the untreated groups, the addition of these small molecules generally reduced viable cell density but increased vector productivity. The positive candidates were BX795 (a TBK inhibitor), TPCA-1 (an IKK2 inhibitor), Cyt387 (a JAK1 inhibitor), and ruxolitinib (another JAK1 inhibitor). These candidates were identified using deep well screening, and reproducible titer improvement was achieved in a 30 mL shake flask scale. Additionally, genome titer improvement is feasible and scalable in two different media, but the extent of improvement may vary.

01 Feb 2025·Bioactive Materials

Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling

Article

Author: Chen, Jialin ; Zhang, Wei ; Lu, Zhiyuan ; Qi, Yu ; Zheng, Haotian ; Zhang, Yanan ; Cao, Zhicheng ; Backman, Ludvig J. ; Backman, Ludvig J ; Mo, Qingyun ; Rui, Yunfeng ; Long, Qiuzi ; Liu, Chuanquan ; Cao, Mumin ; Chen, Zhixuan ; Sheng, Renwang

Tendon repair remains challenging due to its poor intrinsic healing capacity, and stem cell therapy has emerged as a promising strategy to promote tendon regeneration. Nevertheless, the inflammatory environment following acute tendon injuries disrupts stem cell differentiation, leading to unsatisfied outcomes. Our study recognized the critical role of NF-κB signaling in activating inflammation and suppressing tenogenic differentiation of stem cells after acute tendon injury via multiomics analysis. TPCA-1, a selective inhibitor of IKKβ/NF-κB signaling, efficiently restored the impaired tenogenesis of stem cells in the inflammatory environment. By developing a microsphere-incorporated hydrogel system for stem cell delivery and controlled release of TPCA-1, we successfully engineered a pro-tenogenic niche to initiate tenogenesis for tendon regeneration. Collectively, we recognize NF-κB signaling as a critical target to tailor a pro-tenogenic niche and propose the combined delivery of stem cells and TPCA-1 as a potential strategy for acute tendon injuries.

100 Deals associated with TPCA-1

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Rheumatoid Arthritis	Preclinical	United Kingdom	GSK Plc	17 Aug 2004

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

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

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

TPCA-1

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation