Discovery of potential novel CRBN modulators by virtual screening and bioassay.
Sign Up to like & getrecommendations! Published in 2022 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2022.114355
Abstract: The incidence of malignant tumor with high mortality is increasing yearly. CRBN E3 ubiquitin ligase was proved to be an antitumor target. It was found that thalidomide and its analogs could bind to CRBN E3… read more here.
Keywords: modulators virtual; crbn; virtual screening; crbn modulators ... See more keywords
Novel CRBN-Recruiting Proteolysis-Targeting Chimeras as Degraders of Stimulator of Interferon Genes with In Vivo Anti-Inflammatory Efficacy.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c01948
Abstract: The activation of the cyclic GMP-AMP synthase-stimulator of interferon gene (STING) pathway has been associated with the pathogenesis of many autoimmune and inflammatory disorders, and small molecules targeting STING have emerged as a new therapeutic… read more here.
Keywords: crbn; stimulator interferon; anti inflammatory; proteolysis targeting ... See more keywords
De-Novo Design of Cereblon (CRBN) Effectors Guided by Natural Hydrolysis Products of Thalidomide Derivatives
Sign Up to like & getrecommendations! Published in 2019 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.9b00454
Abstract: Targeted protein degradation via cereblon (CRBN), a substrate receptor of an E3 ubiquitin ligase complex, is an increasingly important strategy in various clinical settings, in which the substrate specificity of CRBN is altered via the… read more here.
Keywords: crbn effectors; crbn; cereblon crbn; substrate ... See more keywords
Cereblon gene variants and clinical outcome in multiple myeloma patients treated with lenalidomide
Sign Up to like & getrecommendations! Published in 2019 at "Scientific Reports"
DOI: 10.1038/s41598-019-51446-9
Abstract: Carfilzomib-lenalidomide-dexamethasone (KRd) therapy has yielded promising results in patients with newly diagnosed multiple myeloma (NDMM). Cereblon (CRBN) is the direct molecular target of lenalidomide and genetic polymorphisms in CRBN have been associated with lenalidomide efficacy.… read more here.
Keywords: therapy; cereblon; multiple myeloma; crbn ... See more keywords
PLZF and its fusion proteins are pomalidomide-dependent CRBN neosubstrates
Sign Up to like & getrecommendations! Published in 2021 at "Communications Biology"
DOI: 10.1038/s42003-021-02801-y
Abstract: Pomalidomide and lenalidomide are immunomodulatory agents that were derived from thalidomide. Cereblon (CRBN) is a common direct target of thalidomide and related compounds and works as a Cullin Ring 4 E3 ubiquitin ligase (CRL4) with… read more here.
Keywords: crbn; fusion proteins; proteins pomalidomide; pomalidomide dependent ... See more keywords
Discovery of CRBN as a target of thalidomide: a breakthrough for progress in the development of protein degraders.
Sign Up to like & getrecommendations! Published in 2022 at "Chemical Society reviews"
DOI: 10.1039/d2cs00116k
Abstract: Progress in strategies aimed at breaking down therapeutic target proteins has led to a paradigm shift in drug discovery. Thalidomide and its derivatives are the only protein degraders currently used in clinical practice. Our understanding… read more here.
Keywords: thalidomide derivatives; crbn; progress; protein degraders ... See more keywords
Cereblon contributes to cardiac dysfunction by degrading Cav1.2α.
Sign Up to like & getrecommendations! Published in 2022 at "European heart journal"
DOI: 10.1093/eurheartj/ehac072
Abstract: AIMS Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that was reported to target ion channel proteins. L-type voltage-dependent Ca2+ channel (LTCC) density and dysfunction is a critical player in heart… read more here.
Keywords: cereblon; cav1; hfref; cardiac dysfunction ... See more keywords
Molecular glue CELMoD compounds are regulators of cereblon conformation
Sign Up to like & getrecommendations! Published in 2022 at "Science"
DOI: 10.1126/science.add7574
Abstract: Cereblon (CRBN) is a ubiquitin ligase (E3) substrate receptor protein co-opted by CRBN E3 ligase modulatory drug (CELMoD) agents that target therapeutically relevant proteins for degradation. Prior crystallographic studies defined the drug-binding site within CRBN’s… read more here.
Keywords: cereblon; celmod compounds; conformation; drug ... See more keywords
A Novel Functional Role for Cereblon in Cardiac Cell-Cell Junction Protein Homeostasis, Function and Arrhythmias
Sign Up to like & getrecommendations! Published in 2023 at "Physiology"
DOI: 10.1152/physiol.2023.38.s1.5734511
Abstract: Desmosomes are cell-cell adhesion junctions that function as mechanical anchors between cardiomyocytes. Loss of desmosomal protein levels and integrity due to desmosomal gene mutations are classically linked to arrhythmogenic cardiomyopathy (AC), an inherited cardiac disease… read more here.
Keywords: cell; protein homeostasis; physiology; cell cell ... See more keywords
Abstract B002: Development of bifunctional CRBN-SOS1 degraders for treatment of mutant KRAS cancers
Sign Up to like & getrecommendations! Published in 2023 at "Molecular Cancer Research"
DOI: 10.1158/1557-3125.ras23-b002
Abstract: Although oncogenic Kirsten rat sarcoma virus (KRAS) was once deemed undruggable, recent advances have revealed promising anti-tumor effects with pan-KRAS and KRAS-mutant specific inhibitors in both preclinical and clinical settings. Despite the success of these… read more here.
Keywords: sos1; sos1 degraders; kras mutant; degradation ... See more keywords
Discovery of a Novel Mechanism of Resistance to Thalidomide Derivatives
Sign Up to like & getrecommendations! Published in 2018 at "Blood"
DOI: 10.1182/blood-2018-99-115110
Abstract: Pharmacologic agents that induce protein degradation represent an emerging and important class of therapeutic agents. Thalidomide and thalidomide derivatives (TDs) function by bringing target proteins and the E3 ubiquitin ligase substrate adaptor CRBN into proximity… read more here.
Keywords: degradation; resistance; crbn; activity ... See more keywords