Histone Deacetylases as Epigenetic Targets for Treating Parkinson’s Disease DOI Creative Commons

Yan Li,

Zhicheng Gu, Shuxian Lin

et al.

Brain Sciences, Journal Year: 2022, Volume and Issue: 12(5), P. 672 - 672

Published: May 21, 2022

Parkinson’s disease (PD) is a chronic progressive neurodegenerative that increasingly becoming global threat to the health and life of elderly worldwide. Although there are some drugs clinically available for treating PD, these treatments can only alleviate symptoms PD patients but cannot completely cure disease. Therefore, exploring other potential mechanisms develop more effective modify course still highly desirable. Over last two decades, histone deacetylases, as an important group epigenetic targets, have attracted much attention in drug discovery. This review focused on current knowledge about deacetylases involved pathophysiology their inhibitors used studies. Further perspectives related small molecules inhibit or degrade treat were also discussed.

Language: Английский

Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy DOI Creative Commons
Yujeong Moon, Seong Ik Jeon, Man Kyu Shim

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(2), P. 411 - 411

Published: Jan. 26, 2023

Proteolysis-targeting chimeras (PROTACs) are rapidly emerging as a potential therapeutic strategy for cancer therapy by inducing the degradation of tumor-overexpressing oncogenic proteins. They can specifically catalyze target proteins recruiting E3 ligases and utilizing ubiquitin-proteasome pathway. Since their mode action is universal, irreversible, recyclable, long-lasting, applicable to ‘undruggable’ proteins, PROTACs gradually replacing role conventional small molecular inhibitors. Moreover, application areas being expanded immunotherapy various types that involved in immunosuppressive tumor microenvironments. However, poor water solubility low cell permeability considerably restrict pharmacokinetic (PK) property, which necessitates use appropriate delivery systems immunotherapy. In this review, general characteristics, developmental status, PK first briefly covered. Next, recent studies on passive or active targeting introduced, effects tumor-targeting ability described. Finally, drug summarized. The adoption an adequate system PROTAC expected accelerate clinical translation PROTACs, well improve its efficacy therapy.

Language: Английский

Citations

22
Recent advances in targeted protein degraders as potential therapeutic agents DOI Open Access
Na Yang, Bo Kong,

Zhaohong Zhu

et al.

Molecular Diversity, Journal Year: 2023, Volume and Issue: 28(1), P. 309 - 333

Published: Feb. 15, 2023

Language: Английский

Citations

22
Targeting the Epidermal Growth Factor Receptor with Molecular Degraders: State-of-the-Art and Future Opportunities DOI

Pritam Maity,

Joydeep Chatterjee,

Kiran T. Patil

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(5), P. 3135 - 3172

Published: Feb. 22, 2023

Epidermal growth factor receptor (EGFR) is an oncogenic drug target and plays a critical role in several cellular functions including cancer cell growth, survival, proliferation, differentiation, motility. Several small-molecule tyrosine kinase inhibitors (TKIs) monoclonal antibodies (mAbs) have been approved for targeting intracellular extracellular domains of EGFR, respectively. However, heterogeneity, mutations the catalytic domain persistent resistance limited their use. Different novel modalities are gaining position limelight anti-EGFR therapeutics to overcome such limitations. The current perspective reflects upon newer modalities, importantly molecular degraders as PROTACs, LYTACs, AUTECs, ATTECs, etc., beginning with snapshot traditional existing therapies small molecule inhibitors, mAbs, antibody conjugates (ADCs). Further, special emphasis has made on design, synthesis, successful applications, state-of-the-art, emerging future opportunities each discussed modality.

Language: Английский

Citations

21
Novel strategies and promising opportunities for targeted protein degradation: An innovative therapeutic approach to overcome cancer resistance DOI

Huanjie Zhu,

Jin Wang, Qingqing Zhang

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 244, P. 108371 - 108371

Published: March 5, 2023

Language: Английский

Citations

20
Structure-activity relationship study of RSL3-based GPX4 degraders and its potential noncovalent optimization DOI

Cangxin Zheng,

Chao Wang, Dan Sun

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 255, P. 115393 - 115393

Published: April 21, 2023

Language: Английский

Citations

20
The recent advance of Interleukin-1 receptor associated kinase 4 inhibitors for the treatment of inflammation and related diseases DOI

Yi‐Ru Bai,

Weiguang Yang, Xuehui Hou

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 258, P. 115606 - 115606

Published: June 28, 2023

Language: Английский

Citations

20
Discovery of BWA-522, a First-in-Class and Orally Bioavailable PROTAC Degrader of the Androgen Receptor Targeting N-Terminal Domain for the Treatment of Prostate Cancer DOI
Bowen Zhang,

Chang Liu,

Zhenqian Yang

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(16), P. 11158 - 11186

Published: Aug. 9, 2023

We report small molecular PROTAC compounds targeting the androgen receptor N-terminal domain (AR-NTD), which were obtained by tethering AR-NTD antagonists and different classes of E3 ligase ligands through chemical linkers. A representative compound, BWA-522, effectively induces degradation both AR-FL AR-V7 is more potent than corresponding antagonist against prostate cancer (PC) cells in vitro. have shown that proteins BWA-522 can suppress expression AR downstream induce PC cell apoptosis. achieves 40.5% oral bioavailability mice 69.3% beagle dogs. In a LNCaP xenograft model study, was also proved to be an efficacious degrader, resulting 76% tumor growth inhibition after administration dose 60 mg/kg. This study indicates promising for treatment AR-FL- AR-V7-dependent tumors.

Language: Английский

Citations

20
Targeted protein degradation in drug development: Recent advances and future challenges DOI
Jian H. Song, Mingzheng Hu, Jun Zhou

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 261, P. 115839 - 115839

Published: Sept. 27, 2023

Language: Английский

Citations

18
Research progress of PROTACs for neurodegenerative diseases therapy DOI

Zhifang Cai,

Zunhua Yang,

Huilan Li

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 147, P. 107386 - 107386

Published: April 18, 2024

Language: Английский

Citations

8
Recent Progress in DNA Damage Response-Targeting PROTAC Degraders DOI
Binbin Cheng, Xiaoting Fei, Zongbao Ding

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(9), P. 6906 - 6921

Published: April 25, 2024

DNA damage response (DDR) defects in cells play a crucial role tumor development by promoting mutations. These mutations create vulnerabilities specific to cancer cells, which can be effectively targeted through synthetic lethality-based therapies. To date, numerous small molecule DDR inhibitors have been identified, and some of them already approved for clinical use. However, due the complexity microenvironment, may occur amino acid residues targets. affect efficacy targeting pathways. Therefore, researchers turned their attention next-generation repair modulators, particularly those based on PROTAC technology. From this perspective, we overviewed recent progress DDR-targeting degraders therapy. In addition, also summarized biological functions different Finally, challenges future directions DDR-target are discussed detail.

Language: Английский

Citations

6