Author: Lee, Yu Jin ; Kim, Kyung Won ; Lee, Soon Min ; Kim, Min Jung ; Kim, Eun Gyul ; Song, Tae Won ; Ko, Byung Chan ; Park, Chang Hyun ; Cho, Joo Yeon ; Kim, Yoon Hee ; Sohn, Myung Hyun ; Kim, Mi Na

PURPOSEOxygen therapy is helpful for patients with breathing difficulties; however, sustained supplementation with high-concentration oxygen can cause hyperoxic acute lung injury. Sirtuin 2 (SIRT2), a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, has been shown to be involved in pulmonary fibrosis, apoptosis, and inflammation. Here, we elucidated the role of SIRT2 in hyperoxic acute lung injury.METHODSWild-type (WT) mice and SIRT2-deficient (SIRT2^-/-) mice were exposed to room air or hyperoxia for 72 h. Thereafter, changes in hyperoxia-induced responses were evaluated in WT and SIRT2^-/- mice.RESULTSSIRT2 expression was elevated in WT mice after hyperoxic exposure. We also observed that the levels of SIRT2 were higher in tracheal aspirates from newborns with bronchopulmonary dysplasia (BPD) than in those without BPD. Hyperoxia-induced inflammation and apoptosis were more considerably attenuated in SIRT2^-/- mice than in WT mice. We also observed an interaction between SIRT2 and forkhead box O3 (FOXO3), and that SIRT2 deficiency was associated with altered acetylation levels of FOXO3 and changes in the expression of its downstream targets. Further investigation of the therapeutic effect of SIRT2 showed that hyperoxic acute lung injury was alleviated when AGK2, a SIRT2 inhibitor, was administered.CONCLUSIONTaken together, SIRT2 plays a critical role in the pathogenesis of hyperoxic acute lung injury by regulating apoptotic signaling. These findings indicated that SIRT2 is potentially a novel therapeutic strategy for hyperoxic acute lung injury.

01 May 2025·Biochemical and Biophysical Research Communications

Hunting potential SIRT2 inhibitors towards cancer treatment: Drug repurposing, molecular dynamics, and binding energy computations

Article

Author: Arzumanyan, Grigory ; Abdeljawaad, Khlood A A ; Abdelbacki, Ashraf M M ; Ibrahim, Mahmoud A A ; Hegazy, Mohamed-Elamir F ; Mekhemer, Gamal A H ; Sidhom, Peter A ; Abdelrahman, Alaa H M ; Sayed, Shaban R M

The histone deacetylase group of proteins, which includes the sirtuins, contributes to several cellular processes and is intimately involved in cancer development. Sirtuins type two (SIRT2) is a constituent of the human sirtuin family, which modulates a range of biological functions and is recognized as a potential biomarker for numerous cancers. The impact of SIRT2 knockout on tumorigenesis is debated and varies with the type of tumor; nonetheless, pharmacological inhibition of SIRT2 results exclusively in growth inhibition of diverse cancer cell lines. As a result, SIRT2 regulation is thought to be a viable protein for treating cancer. Herein, the DrugBank database, containing >14,000 drug molecules, was repurposed to find potential anticancer medications that have the capacity to inhibit the SIRT2 protein utilizing in-silico techniques. In light of the experimental findings, the capability of AutoDock Vina1.1.2 software to anticipate the docking scores and poses of the SIRT2 inhibitors was assessed. SirReal2, a potential SIRT2 inhibitor, was the controller for this study. Notably, drugs with docking scores less than SiReal2 were chosen and introduced to molecular dynamics (MD) simulations, accompanied by binding affinities estimations utilizing the MM-GBSA approach. Interestingly, MM-GBSA calculations demonstrated that five drugs, namely DB11526, DB11977, DB15133, DB04739, and DB04632, revealed potential affinities as SIRT2 inhibitors exhibiting ΔG_binding less than -50.0 kcal/mol. The post-MD analyses were inspected for DB11526, DB11977, DB15133, DB04739, and DB04632, indicating excellent steadiness of these drugs bound to SIRT2 protein throughout the 200 ns MD. The ADMET features were also examined and were acceptable. These findings suggested that more attention should be paid to DB11526, DB11977, DB15133, DB04739, and DB04632 as SIRT2 inhibitors utilizing in-vitro/in-vivo assays to treat cancer disease.

01 Apr 2025·Analytical Chemistry

Novel Cyclopropene Probes as Chemical Reporters for Bioorthogonal Metabolic Labeling of Benzoylated Post-Translational Modification

Article

Author: Zhang, Qingqing ; Li, Yan ; Li, Ruixi ; Luo, Yongxiang ; Chen, Lei ; Luo, Qinggen ; He, Bin ; Liu, Ting ; Jin, Fei

Lysine benzoylation (Kbz) is a recently identified post-translational modification on a histone that plays a crucial role in regulating cellular processes. Current detection methods primarily rely on mass spectrometry, which limits the ability to dynamically track lysine benzoylation within living cells. Although azide/alkyne small-sized probes have enabled in vitro labeling of various protein acylated modifications, their use in dynamic tracking in cellular levels is limited. Herein, we report a novel 1-methylcyclopropene chemical reporter that undergoes an IEDDA reaction with S-tetrazine-BODIPY 8, which was evaluated for its optical properties, kinetic constants, and bio-orthogonality, revealing it to be the most efficient benzoic acid probe 2. In addition, when SIRT2 acts on the peptides labeled with probe 2, the kinetic parameters of these peptides are comparable to those of endogenously benzoylated peptides. Finally, the metabolic labeling of lysine benzoylation was successfully validated in RAW and HepG2 cells using probe 2. Furthermore, by using a SIRT2 inhibitor, it was confirmed that this metabolic labeling can be applied to dynamically detect changes in lysine benzoylation levels in cells. These findings provide a solid foundation for the development of novel metabolic labeling strategies for dynamically tracking post-translational modifications, particularly in live cells.

100 Deals associated with SIRT2 inhibitors(University of Freiburg)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Discovery	United States	University of Freiburg	07 Jun 2024

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

SIRT2 inhibitors(University of Freiburg)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation