Covalent inhibitor targets KRasG12C: A new paradigm for drugging the undruggable and challenges ahead

Covalent inhibitor targets KRasG12C: A new paradigm for drugging the undruggable and challenges ahead

KRAS is one of the most commonly mutated oncogenes in cancers and therapeutics directly targeting the KRas have been challenging. Among the different known mutants, KRasG12C has been proved to be successfully targeted recently. Several covalent inhibitors selectively targeting KRasG12C have shown pr...

Full description

Bibliographic Details
Main Authors:	Hui-yu Li, Wei-liang Qi, Yu-xiang Wang, Ling-hua Meng
Format:	Article
Language:	English
Published:	KeAi Communications Co., Ltd. 2023-03-01
Series:	Genes and Diseases
Subjects:	Biomarkers Covalent KRasG12Cinhibitors Drug resistance Human cancers KRASG12Cmutation
Online Access:	http://www.sciencedirect.com/science/article/pii/S2352304221001094

Similar Items

Naproxen inhibits spontaneous lung adenocarcinoma formation in KrasG12V mice
by: Gaurav Kumar, et al.
Published: (2021-06-01)

Multiscale calculations reveal new insights into the reaction mechanism between KRASG12C and α, β-unsaturated carbonyl of covalent inhibitors
by: Xiao Yan, et al.
Published: (2024-12-01)

Outcomes following KRASG12C inhibitor treatment in patients with KRASG12C-mutated solid tumors: A systematic review and meta-analysis
by: Qi-An Chen, et al.
Published: (2024-02-01)

Efficacy and Safety of KRASG12C Inhibitors in Advanced Solid Tumors with KRASG12C-mutated: A Single-arm Meta-analysis
by: TAN Dengxu, et al.
Published: (2023-07-01)

Discovery of potent and noncovalent KRASG12D inhibitors: Structure-based virtual screening and biological evaluation
by: Yuting Wang, et al.
Published: (2022-12-01)

The path to the clinic: a comprehensive review on direct KRASG12C inhibitors
by: Albert K. Kwan, et al.
Published: (2022-01-01)

BCL-XL PROTAC degrader DT2216 synergizes with sotorasib in preclinical models of KRASG12C-mutated cancers
by: Sajid Khan, et al.
Published: (2022-03-01)

Establishing the mutational effect on the binding susceptibility of AMG510 to KRAS switch II binding pocket: Computational insights
by: Abdul Rashid Issahaku, et al.
Published: (2022-01-01)

Development of a biotin–streptavidin-enhanced enzyme-linked immunosorbent assay (BA-ELISA) for high-throughput screening of KRASG12C inhibitors
by: Shuang Liu, et al.
Published: (2022-03-01)

Understanding the influence of AMG 510 on the structure of KRASG12C empowered by molecular dynamics simulation
by: Yu Li, et al.
Published: (2022-01-01)

KRAS inhibitors: going noncovalent
by: Matthias Drosten, et al.
Published: (2022-12-01)

Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels
by: Bo eKong, et al.
Published: (2013-09-01)

Targeting Mutant Kirsten Rat Sarcoma Viral Oncogene Homolog in Non-Small Cell Lung Cancer: Current Difficulties, Integrative Treatments and Future Perspectives
by: Jia-Xin Li, et al.
Published: (2022-04-01)

Spotlight on Sotorasib (AMG 510) for KRASG12C Positive Non-Small Cell Lung Cancer
by: Zhang S, et al.
Published: (2021-10-01)

KSR induces RAS‐independent MAPK pathway activation and modulates the efficacy of KRAS inhibitors
by: Guillem Paniagua, et al.
Published: (2022-09-01)

Early detection of pre-malignant lesions in a KRASG12D-driven mouse lung cancer model by monitoring circulating free DNA
by: Callum P. Rakhit, et al.
Published: (2019-02-01)

CodeBreak 200: Sotorasib Has Not Broken the KRASG12C Enigma Code
by: Zhang SS, et al.
Published: (2023-04-01)

Apoptosis-inducing activity of synthetic hydrocarbon-stapled peptides in H358 cancer cells expressing KRASG12C
by: Cuicui Li, et al.
Published: (2021-09-01)

Targeting ST8SIA6-AS1 counteracts KRASG12C inhibitor resistance through abolishing the reciprocal activation of PLK1/c-Myc signaling
by: Yafang Wang, et al.
Published: (2023-12-01)

Pancreatic HIF2α Stabilization Leads to Chronic Pancreatitis and Predisposes to Mucinous Cystic Neoplasm
by: Heather K. Schofield, et al.
Published: (2018-01-01)

Co-occurring KRAS mutation/LKB1 loss in non-small cell lung cancer cells results in enhanced metabolic activity susceptible to caloric restriction: an in vitro integrated multilevel approach
by: Elisa Caiola, et al.
Published: (2018-12-01)

Targeting KRAS mutant lung cancer: light at the end of the tunnel
by: Matthias Drosten, et al.
Published: (2022-03-01)

Pharmacokinetics of the KRASG12C inhibitor adagrasib is limited by CYP3A and ABCB1, and influenced by binding to mouse plasma carboxylesterase 1c
by: Nancy H.C. Loos, et al.
Published: (2023-10-01)

Computer-aided drug design of some KRAS G12C inhibitors: Targeting the covalent and allosteric binding site for cancer therapy
by: Abdeen Tunde Ogunlana, et al.
Published: (2022-01-01)

KRAS G12D targeted therapies for pancreatic cancer: Has the fortress been conquered?
by: Sahar F. Bannoura, et al.
Published: (2022-11-01)

Kristen rat sarcoma virus (KRAS) G12F‐positive non‐small cell lung cancer mimicking KRAS G12C positivity: A case report
by: Issei Oi, et al.
Published: (2024-01-01)

Targeting oncogenic KRasG13C with nucleotide-based covalent inhibitors
by: Lisa Goebel, et al.
Published: (2023-03-01)

Drugging the Undruggable: Advances on RAS Targeting in Cancer
by: Miriam Molina-Arcas, et al.
Published: (2021-06-01)

Mechanisms of Resistance to KRAS<sup>G12C</sup> Inhibitors
by: Victoria Dunnett-Kane, et al.
Published: (2021-01-01)

Morphological and Molecular Characterization of KRAS G12C-Mutated Lung Adenocarcinomas
by: Radu Pirlog, et al.
Published: (2022-02-01)

KRASG12C inhibition using MRTX1257: a novel radio-sensitizing partner
by: Pierre-Antoine Laurent, et al.
Published: (2023-10-01)

<i>A First-Class Degrader Candidate Targeting Both</i> KRAS G12D and G12V Mediated by CANDDY Technology Independent of Ubiquitination
by: Etsuko Miyamoto-Sato, et al.
Published: (2023-07-01)

A Breakthrough Brought about by Targeting KRAS<sup>G12C</sup>: Nonconformity Is Punished
by: Wenjuan Ning, et al.
Published: (2022-01-01)

KRAS G12C Mutations in NSCLC: From Target to Resistance
by: Alfredo Addeo, et al.
Published: (2021-05-01)

Design, synthesis, and evaluation of purine and pyrimidine-based KRAS G12D inhibitors: Towards potential anticancer therapy
by: So-Youn Park, et al.
Published: (2024-04-01)

KRAS Codon 12 and 13 Mutations in Gastric Cancer in the Northeast Iran
by: Hossein Ayatollahi, et al.
Published: (2018-04-01)

Targeting KRAS in NSCLC: Old Failures and New Options for “Non-G12c” Patients
by: Francesca Jacobs, et al.
Published: (2021-12-01)

Bispecific T cell engagers kill resistant cells during KRAS-G12C blockade therapy
by: Xinxin Song, et al.
Published: (2022-12-01)

How to manage KRAS G12C-mutated advanced non-small-cell lung cancer
by: Biagio Ricciuti, et al.
Published: (2022-11-01)

Light at the end of the tunnel: Clinical features and therapeutic prospects of KRAS mutant subtypes in non-small-cell lung cancer
by: Liyuan Gao, et al.
Published: (2022-10-01)