-
Jul 28, 2024 | 
nature.com | Moritz Hunkeler |Mingxing Teng |Justine C. Rutter |Anna M Schmoker |Rebecca Metivier |Woong Sub Byun | +9 more
AbstractMolecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed ‘template-assisted covalent modification’.
-
Jun 19, 2024 | 
mdpi.com | Chuankai Chen |Ya-Ping Jiang |Inchul You |Nathanael S. Gray
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
-
Jun 18, 2024 | 
nature.com | Han-Yuan Liu |Theresia Reindl |Ryan Golden |Katherine A. Donovan |Eric S. Fischer |Nathanael S. Gray
AbstractViral genetic diversity presents significant challenges in developing antivirals with broad-spectrum activity and high barriers to resistance. Here we report development of proteolysis targeting chimeras (PROTACs) targeting the dengue virus envelope (E) protein through coupling of known E fusion inhibitors to ligands of the CRL4CRBN E3 ubiquitin ligase.
-
May 5, 2024 | 
biorxiv.org | Ya-Ping Jiang |Inchul You |Nathanael S. Gray |Chuankai Chen
AbstractSerine/threonine kinase AKT isoforms play a well-established role in cell metabolism and growth. Most pancreatic adenocarcinoma (PDAC) harbors activation mutations of KRAS, which activates the PI3K/AKT signaling pathway. However, AKT inhibitors are not effective in the treatment of pancreatic cancer.
-
Apr 29, 2024 | 
nature.com | Raymond Carter |Baranda S. Hansen |Katherine A. Donovan |Moritz Hunkeler |Wojciech Rosikiewicz |Meghan G. McReynolds | +8 more
Correction to: Nature https://doi.org/10.1038/s41586-024-07250-1 Published online 27 March 2024In the version of the article initially published, the far-right labels in Fig. 4h (now reading “Viable cells” and “Lethal in SMARCB1-deficient RT cells”) were swapped and have now been corrected in the HTML and PDF versions of the article. About this articleRadko-Juettner, S., Yue, H., Myers, J.A. et al. Author Correction: Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF.
-
Apr 15, 2024 | 
nature.com | Fabin Dang |Lin Wang |Wenxue Li |Felipe Batalini |Jaymin Patel |John G. Clohessy | +4 more
AbstractInduced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/CCDH1) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/CCDH1 activity to treat cancer.
-
Mar 27, 2024 | 
nature.com | Raymond Carter |Baranda S. Hansen |Katherine A. Donovan |Moritz Hunkeler |Wojciech Rosikiewicz |Nada Mageed | +8 more
AbstractWhereas oncogenes can potentially be inhibited with small molecules, the loss of tumour suppressors is more common and is problematic because the tumour-suppressor proteins are no longer present to be targeted. Notable examples include SMARCB1-mutant cancers, which are highly lethal malignancies driven by the inactivation of a subunit of SWI/SNF (also known as BAF) chromatin-remodelling complexes.
-
Mar 7, 2024 | 
nature.com | Guang Yang |Sara J. Buhrlage |Jinhua Wang |Nathanael S. Gray |Marie José Kersten |Steven P. Treon
AbstractAlthough Bruton’s tyrosine kinase (BTK) inhibitors (BTKi) have significantly improved patient prognosis, mantle cell lymphoma (MCL) is still considered incurable due to primary and acquired resistance. We have recently shown that aberrant expression of the Src-family tyrosine kinase hematopoietic cell kinase (HCK) in MCL correlates with poor prognosis, and that genetic HCK perturbation impairs growth and integrin-mediated adhesion of MCL cells.
-
Feb 27, 2024 | 
science.org | Emily Erickson |Hao Cai |Leslie K. Ferrarelli |Inchul You |Grace Perry |Aurelien Dugourd | +11 more
Research ResourceCANCEREmily C. Erickson https://orcid.org/0000-0003-3494-2605, Inchul You, [...] , Grace Perry https://orcid.org/0000-0002-0404-9237, Aurelien Dugourd https://orcid.org/0000-0002-0714-028X, [...] , Katherine A. Donovan https://orcid.org/0000-0002-8539-5106, Claire Crafter https://orcid.org/0000-0001-6566-0868, Jeffrey W. Johannes https://orcid.org/0000-0001-7242-6682, Stuart Williamson https://orcid.org/0000-0002-5209-4796, Jennifer I.
-
Feb 27, 2024 | science.org | Emily Erickson |Hao Cai |Leslie K. Ferrarelli |Inchul You |Grace Perry |Aurelien Dugourd | +11 more
Research ResourceCANCEREmily C. Erickson https://orcid.org/0000-0003-3494-2605, Inchul You, [...] , Grace Perry https://orcid.org/0000-0002-0404-9237, Aurelien Dugourd https://orcid.org/0000-0002-0714-028X, [...] , Katherine A. Donovan https://orcid.org/0000-0002-8539-5106, Claire Crafter https://orcid.org/0000-0001-6566-0868, Jeffrey W. Johannes https://orcid.org/0000-0001-7242-6682, Stuart Williamson https://orcid.org/0000-0002-5209-4796, Jennifer I.
