Cargando…

Targeting oncogenic KRasG13C with nucleotide-based covalent inhibitors

Mutations within Ras proteins represent major drivers in human cancer. In this study, we report the structure-based design, synthesis, as well as biochemical and cellular evaluation of nucleotide-based covalent inhibitors for KRasG13C, an important oncogenic mutant of Ras that has not been successfu...

Descripción completa

Detalles Bibliográficos
Autores principales:	Goebel, Lisa, Kirschner, Tonia, Koska, Sandra, Rai, Amrita, Janning, Petra, Maffini, Stefano, Vatheuer, Helge, Czodrowski, Paul, Goody, Roger S, Müller, Matthias P, Rauh, Daniel
Formato:	Online Artículo Texto
Lenguaje:	English
Publicado:	eLife Sciences Publications, Ltd 2023
Materias:	Biochemistry and Chemical Biology
Acceso en línea:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10042540/ https://www.ncbi.nlm.nih.gov/pubmed/36972177 http://dx.doi.org/10.7554/eLife.82184

Ejemplares similares

KRasG12C inhibitors in clinical trials: a short historical perspective
por: Goebel, Lisa, et al.
Publicado: (2020)

Role and regulation of Yap in KrasG12D-induced lung cancer
por: Mao, Yaopan, et al.
Publicado: (2017)

Covalent disruptor of YAP-TEAD association suppresses defective Hippo signaling
por: Fan, Mengyang, et al.
Publicado: (2022)

Mechanisms of nucleotide selection by telomerase
por: Schaich, Matthew A, et al.
Publicado: (2020)

Nucleotide based covalent inhibitors of KRas can only be efficient in vivo if they bind reversibly with GTP-like affinity
por: Müller, Matthias P., et al.
Publicado: (2017)

Addition of metabolomics to the omics spectrum for cancer biomarker development– demonstration with the KrasG12D mouse model for pancreatic carcinoma
por: Laiakis, Evagelia C, et al.
Publicado: (2014)

bMERB domains are bivalent Rab8 family effectors evolved by gene duplication
por: Rai, Amrita, et al.
Publicado: (2016)

PH domain-mediated autoinhibition and oncogenic activation of Akt
por: Bae, Hwan, et al.
Publicado: (2022)

FOXP2 confers oncogenic effects in prostate cancer
por: Zhu, Xiaoquan, et al.
Publicado: (2023)

Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma
por: Brien, Gerard L, et al.
Publicado: (2018)

An acquired scaffolding function of the DNAJ-PKAc fusion contributes to oncogenic signaling in fibrolamellar carcinoma
por: Turnham, Rigney E, et al.
Publicado: (2019)

Covalent inhibition of endoplasmic reticulum chaperone GRP78 disconnects the transduction of ER stress signals to inflammation and lipid accumulation in diet-induced obese mice
por: Luo, Dan, et al.
Publicado: (2022)

Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation
por: Rousová, Dorota, et al.
Publicado: (2021)

Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion
por: Shin, Donghyuk, et al.
Publicado: (2017)

Diverse functions of homologous actin isoforms are defined by their nucleotide, rather than their amino acid sequence
por: Vedula, Pavan, et al.
Publicado: (2017)

The dynamic interplay of host and viral enzymes in type III CRISPR-mediated cyclic nucleotide signalling
por: Athukoralage, Januka S, et al.
Publicado: (2020)

Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice
por: Xu, Mu, et al.
Publicado: (2018)

MicroRNA 3′-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position
por: McGeary, Sean E, et al.
Publicado: (2022)

Electroporated recombinant proteins as tools for in vivo functional complementation, imaging and chemical biology
por: Alex, Amal, et al.
Publicado: (2019)

A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1
por: Vercoulen, Yvonne, et al.
Publicado: (2017)

A point mutation in the nucleotide exchange factor eIF2B constitutively activates the integrated stress response by allosteric modulation
por: Boone, Morgane, et al.
Publicado: (2022)

VSFlow: an open-source ligand-based virtual screening tool
por: Jung, Sascha, et al.
Publicado: (2023)

Covalent Immobilization of Proteins for the Single Molecule Force Spectroscopy
por: Becke, Tanja D., et al.
Publicado: (2018)

Saccharomyces cerevisiae DJ-1 paralogs maintain genome integrity through glycation repair of nucleic acids and proteins
por: Susarla, Gautam, et al.
Publicado: (2023)

Incidence of pancreatic cancer is dramatically increased by a high fat, high calorie diet in KrasG12D mice
por: Chang, Hui-Hua, et al.
Publicado: (2017)

Molecular mechanism of active Cas7-11 in processing CRISPR RNA and interfering target RNA
por: Goswami, Hemant N, et al.
Publicado: (2022)

Immunoproteasome functions explained by divergence in cleavage specificity and regulation
por: Winter, Michael B, et al.
Publicado: (2017)

The orphan ligand, activin C, signals through activin receptor-like kinase 7
por: Goebel, Erich J, et al.
Publicado: (2022)

Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model
por: Chang, Hui-Hua, et al.
Publicado: (2018)

Glypican-1 drives unconventional secretion of fibroblast growth factor 2
por: Sparn, Carola, et al.
Publicado: (2022)

Oncogenic KRAS G12C: Kinetic and redox characterization of covalent inhibition
por: Huynh, Minh V., et al.
Publicado: (2022)

Agl24 is an ancient archaeal homolog of the eukaryotic N-glycan chitobiose synthesis enzymes
por: Meyer, Benjamin H, et al.
Publicado: (2022)

Autoregulatory control of microtubule binding in doublecortin-like kinase 1
por: Agulto, Regina L, et al.
Publicado: (2021)

The role of Cdc42 and Gic1 in the regulation of septin filament formation and dissociation
por: Sadian, Yashar, et al.
Publicado: (2013)

Molecular and Functional Characteristics of Ovarian Surface Epithelial Cells Transformed by KrasG12D and loss of Pten in a Mouse Model in vivo
por: Mullany, Lisa K., et al.
Publicado: (2011)

Low dosage combination treatment with metformin and simvastatin inhibits obesity-promoted pancreatic cancer development in male KrasG12D mice
por: Teper, Yaroslav, et al.
Publicado: (2023)

Analyzing native membrane protein assembly in nanodiscs by combined non-covalent mass spectrometry and synthetic biology
por: Henrich, Erik, et al.
Publicado: (2017)

Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop
por: Aykul, Senem, et al.
Publicado: (2020)

Identification of FEZ2 as a potential oncogene in pancreatic ductal adenocarcinoma
por: Yang, Chaozhi, et al.
Publicado: (2022)

Oncogenic KRAS supports pancreatic cancer through regulation of nucleotide synthesis
por: Santana-Codina, Naiara, et al.
Publicado: (2018)

Cannot write session to /tmp/vufind_sessions/sess_nl4k9leh5qhk3t7cqcv5fqckp1