Attenuation of NLRP3 Inflammasome Activation by Indirubin-Derived PROTAC Targeting HDAC6

Cao, Zhengxuan; Gu, Zhicheng; Lin, Shuxian; Chen, Di; Wang, Jie; Zhao, Yong‐Long; Li, Yan; Liu, Ting; Li, Yongjun; Wang, Yi; Lin, Hening; He, Bin

doi:10.1021/acschembio.1c00681

Cited by 37 publications

(41 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Leukocytosis is associated with atherosclerotic disease severity, which is also reported to be related to unstable plaques and elicits acute thrombotic events [ 26 ]. Endothelial responses are featured by elevated expressions of proinflammatory cytokines and cellular adhesion molecules in atherosclerotic lesions, which promote activation and accumulation of leukocytes [ 27 ]. An inflammatory reaction is elicited by tissue hypoxia in the brain parenchyma of cases with acute ischemic stroke [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Value of the Prognostic Nutrition Index in the Assessment of Prognosis in Critically Ill Patients with Stroke: A Retrospective Analysis

Liu

Yang

Kadasah

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Purpose. The purpose of study was to evaluate the association between prognostic nutritional index (PNI) and all-cause mortality of critically ill patients with stroke. Methods. Clinical data derived from Multiparameter Intelligent Monitoring in Intensive Care were analyzed. The primary endpoint was 30-day all-cause mortality; secondary endpoints were 90-day mortality and one-year cause mortality. The potential prognostic roles of PNI were analyzed by Cox proportional hazard models. The independent prognostic roles of PNI in the cases were analyzed by smooth curve fitting. Results. Concerning 30-day mortality, the HR (95% CI) for a high PNI (≥39.7) was 0.700 (0.544, 0.900; P = 0.00539 ), compared to a low PNI (<39.7). After adjusting for multiple confounders, the HR (95% CI) for a high PNI (≥39.7) was 0.732 (0.547, 0.978; P = 0.03514 ), compared to a low PNI (<39.7). Regarding 90-day and one-year mortality, a similar trend was observed. In addition, a nonlinear association between PNI and 30-day mortality was found. Using recursive algorithm and two-piecewise linear regression model, inflection point (IP) was calculated, which was 49.4. On the right side of the IP, there was a positive relationship between PNI and 30-day mortality, and the effect size, 95% CI, and P value were 1.04 (1.01, 1.07), P = 0.0429 , respectively. On the left of the IP, the effect size, 95% CI, and P value were 0.97 (0.96, 0.99) and 0.0011, respectively. Conclusions. The PNI was an independent predicting factor of 30-day, 90-day, and 1-year mortality of the critically ill patients with stroke. In addition, there was a U-shaped relationship between PNI and all-cause mortality of stroke patients. PNI was a risk factor for the outcome of stroke when PNI was >49.4, while PNI was a protective factor for outcome of stroke when PNI was <49.4.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical Value of the Prognostic Nutrition Index in the Assessment of Prognosis in Critically Ill Patients with Stroke: A Retrospective Analysis

Liu

Yang

Kadasah

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

show abstract

“…Concurrent degradation of several HDACs still has a risk of unsatisfactory effects [ 56 ]. Hence, targeted degradation of the key pathogenic HDAC subtypes becomes a preferable option [ 56 , 131 , 132 ]. Unlike conventional HDAC proteins that localize in the nucleus, HDAC6 mainly distributes in the cytoplasm and interacts with multiple cytosolic nonhistone proteins, including α-tubulin, and heat shock protein 90 (HSP90) and cortactin [ 133 ].…”

Section: Small-molecule Protacs For Vital Regulatory Proteinsmentioning

confidence: 99%

Small-Molecule PROTACs for Cancer Immunotherapy

Liu¹,

Zhang²,

Xiang³

et al. 2022

Molecules

View full text Add to dashboard Cite

Unsatisfactory physicochemical properties of macromolecular drugs seriously hinder their application in tumor immunotherapy. However, these problems can be effectively solved by small-molecule compounds. In the promising field of small-molecule drug development, proteolysis targeting chimera (PROTAC) offers a Cancer Patients. Bosn. J. Basic novel mode of action in the interactions between small molecules and therapeutic targets (mainly proteins). This revolutionary technology has shown considerable impact on several proteins related to tumor survival but is rarely exploited in proteins associated with immuno-oncology up until now. This review attempts to comprehensively summarize the well-studied and less-developed immunological targets available for PROTAC technology, as well as some targets to be explored, aiming to provide more options and opportunities for the development of small-molecule-based tumor immunotherapy. In addition, some novel directions that can magnify and broaden the protein degradation efficiency are mentioned to improve PROTAC design in the future.

show abstract

“…In 2021, He group also reported another HDAC6 degrader based on CDK/HDAC6 inhibitor derived from Indirubin. 242 They evaluated the degradation activities of HDAC6 in K562 cells. Interestingly, the PROTAC 144 (Fig.…”

Section: Protacs Targeting Cancer-related Targetsmentioning

confidence: 99%

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

Cao

et al. 2022

Sig Transduct Target Ther

112

View full text Add to dashboard Cite

PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin–proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article “PROTACs: great opportunities for academia and industry” in the journal, summarizing the representative compounds of PROTACs reported before the end of 2019. In the past 2 years, the entire field of protein degradation has experienced rapid development, including not only a large increase in the number of research papers on protein-degradation technology but also a rapid increase in the number of small-molecule degraders that have entered the clinical and will enter the clinical stage. In addition to PROTAC and molecular glue technology, other new degradation technologies are also developing rapidly. In this article, we mainly summarize and review the representative PROTACs of related targets published in 2020–2021 to present to researchers the exciting developments in the field of protein degradation. The problems that need to be solved in this field will also be briefly introduced.

show abstract

Attenuation of NLRP3 Inflammasome Activation by Indirubin-Derived PROTAC Targeting HDAC6

Cited by 37 publications

References 38 publications

Clinical Value of the Prognostic Nutrition Index in the Assessment of Prognosis in Critically Ill Patients with Stroke: A Retrospective Analysis

Clinical Value of the Prognostic Nutrition Index in the Assessment of Prognosis in Critically Ill Patients with Stroke: A Retrospective Analysis

Small-Molecule PROTACs for Cancer Immunotherapy

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

Contact Info

Product

Resources

About