Exploiting Cancer Vulnerabilities by Blocking of the DHODH and GPX4 Pathways: A Multifunctional Bodipy/PROTAC Nanoplatform for the Efficient Synergistic Ferroptosis Therapy.
Sign Up to like & getrecommendations! Published in 2023 at "Advanced healthcare materials"
DOI: 10.1002/adhm.202300871
Abstract: Ferroptosis is a form of programmed cell death and plays an important role in many diseases. Dihydroorotate dehydrogenase (DHODH) and glutathione peroxidase 4 (GPX4) play major roles in cell resistance to ferroptosis. Therefore, inactivation of… read more here.
Keywords: ferroptosis therapy; dhodh; protac; gpx4 ... See more keywords
Development of selective mono or dual PROTAC degrader probe of CDK isoforms.
Sign Up to like & getrecommendations! Published in 2019 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2019.111952
Abstract: Cyclin-dependent kinase (CDK) family members are promising molecular targets in discovering potent inhibitors in disease settings, they function differentially. CDK2, CDK4 and CDK6, directly regulate the cell cycle, while CDK9 primarily modulates the transcription regulation.… read more here.
Keywords: degrader; development selective; protac; selective mono ... See more keywords
Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity.
Sign Up to like & getrecommendations! Published in 2020 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2020.112186
Abstract: Anti-apoptotic protein BCL-XL plays a key role in tumorigenesis and cancer chemotherapy resistance, rendering it an attractive target for cancer treatment. However, BCL-XL inhibitors such as ABT-263 cannot be safely used in the clinic because… read more here.
Keywords: abt 263; protac; bcl degraders; target ... See more keywords
Induced protein degradation of histone deacetylases 3 (HDAC3) by proteolysis targeting chimera (PROTAC).
Sign Up to like & getrecommendations! Published in 2020 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2020.112800
Abstract: Histone deacetylases (HDACs) play important roles in inflammatory diseases like asthma and chronic obstructive pulmonary disease (COPD). Unravelling of and interfering with the functions of specific isoenzymes contributing to inflammation provides opportunities for drug development.… read more here.
Keywords: proteolysis targeting; protac; degradation; histone deacetylases ... See more keywords
The state of the art of PROTAC technologies for drug discovery.
Sign Up to like & getrecommendations! Published in 2022 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2022.114290
Abstract: Protein degradation technology has progressed dramatically since 2001 when proteolysis targeting chimera (PROTAC) was first reported. Various of distinctive degradation technologies based on PROTAC have been developed for the degradation of kinases, nuclear receptors, epigenetic… read more here.
Keywords: technologies drug; protac; protac technologies; degradation ... See more keywords
Targeting the C481S Ibrutinib-Resistance Mutation in Bruton's Tyrosine Kinase Using PROTAC-Mediated Degradation.
Sign Up to like & getrecommendations! Published in 2018 at "Biochemistry"
DOI: 10.1021/acs.biochem.8b00391
Abstract: Inhibition of Bruton's tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has emerged as a transformative treatment option for patients with chronic lymphocytic leukemia (CLL) and other B-cell malignancies, yet >80% of CLL patients develop… read more here.
Keywords: degradation; protac; btk; bruton tyrosine ... See more keywords
PRosettaC: Rosetta Based Modeling of PROTAC Mediated Ternary Complexes
Sign Up to like & getrecommendations! Published in 2020 at "Journal of Chemical Information and Modeling"
DOI: 10.1021/acs.jcim.0c00589
Abstract: Proteolysis-targeting chimeras (PROTACs), which induce degradation by recruitment of an E3 ligase to a target protein, are gaining much interest as a new pharmacological modality. However, designing PROTACs is challenging. Formation of a ternary complex… read more here.
Keywords: protein; ternary complex; ternary complexes; protac ... See more keywords
Improved Accuracy for Modeling PROTAC-Mediated Ternary Complex Formation and Targeted Protein Degradation via New In Silico Methodologies.
Sign Up to like & getrecommendations! Published in 2020 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.0c00897
Abstract: Extending upon our previous publication (Drummond, M., Williams, C., In Silico Modeling of PROTAC-mediated Ternary Complexes: Validation and Application, J. Chem. Inf. Model., 2019, 59, 1634-1644), in this work two additional computational methods are presented… read more here.
Keywords: ternary complex; protac mediated; protac; mediated ternary ... See more keywords
Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91.
Sign Up to like & getrecommendations! Published in 2021 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.0c01897
Abstract: Napabucasin, undergoing multiple clinical trials, was reported to inhibit the signal transducer and transcription factor 3 (STAT3). To better elucidate its mechanism of action, we designed a napabucasin-based proteolysis targeting chimera (PROTAC), XD2-149 that resulted… read more here.
Keywords: discovery napabucasin; zfp91; xd2 149; ligase zfp91 ... See more keywords
Discovery of a Potent, Cooperative, and Selective SOS1 PROTAC ZZ151 with In Vivo Antitumor Efficacy in KRAS-Mutant Cancers.
Sign Up to like & getrecommendations! Published in 2023 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.3c00075
Abstract: The linker moiety of a proteolysis-targeting chimera (PROTAC) molecule plays a critical role in modulating the degradation activity, target selectivity, and physico-chemical properties. However, the basics and underlying mechanisms of chemical modifications of the linker… read more here.
Keywords: selective sos1; kras mutant; sos1 protac; protac zz151 ... See more keywords
Native Mass Spectrometry Can Effectively Predict PROTAC Efficacy
Sign Up to like & getrecommendations! Published in 2020 at "ACS Central Science"
DOI: 10.1021/acscentsci.0c00049
Abstract: Protein degraders, also known as proteolysis targeting chimeras (PROTACs), are bifunctional small molecules that promote cellular degradation of a protein of interest (POI). PROTACs act as molecular mediators, bringing an E3 ligase and a POI… read more here.
Keywords: spectrometry effectively; protac; native mass; mass spectrometry ... See more keywords