Related Experiment Video
Updated: Mar 29, 2026
Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
Published on: October 4, 2017
Covalent targeting of acquired cysteines in cancer
Marieke Visscher1, Michelle R Arkin2, Tobias B Dansen1
1Center for Molecular Medicine, Molecular Cancer Research, University Medical Center Utrecht, The Netherlands.
Abstract:
The thiolate side chain of cysteine has a unique functionality that drug hunters and chemical biologists have begun to exploit. For example, targeting cysteine residues in the ATP-binding pockets of kinases with thiol-reactive molecules has afforded increased selectivity and potency to drugs like imbrutinib, which inhibits the oncogene BTK, and CO-1686 and AZD9291 that target oncogenic mutant EGFR. Recently, disulfide libraries and targeted GDP-mimetics have been used to selectively label the G12C oncogenic mutation in KRAS. We reasoned that other oncogenes contain mutations to cysteine, and thus screened the Catalog of Somatic Mutations in Cancer for frequently acquired cysteines. Here, we describe the most common mutations and discuss how these mutations could be potential targets for cysteine-directed personalized therapeutics.
Insights
Cysteine mutations in oncogenes offer new therapeutic targets. Researchers identified common cysteine mutations in cancer, paving the way for targeted personalized medicines.
Area of Science:
- Biochemistry
- Oncology
- Medicinal Chemistry
Background:
- Cysteine's unique thiolate chemistry is increasingly exploited in drug discovery.
- Targeting cysteine residues in kinases has led to potent drugs like imbrutinib (BTK inhibitor) and EGFR inhibitors.
Purpose of the Study:
- To identify frequently mutated cysteines in oncogenes beyond KRAS.
- To explore the potential of these mutations as targets for novel, cysteine-directed therapeutics.
Main Methods:
- Screening the Catalog of Somatic Mutations in Cancer (COSMIC) for frequently acquired cysteine mutations.
- Analyzing mutation data to identify common cysteine alterations in oncogenes.
Main Results:
- Identification of several frequently mutated cysteine residues across various oncogenes.
- Characterization of these mutations as potential targets for selective drug development.
Conclusions:
- Mutations in cysteine residues represent a promising, yet underexplored, class of oncogenic targets.
- Cysteine-directed personalized therapeutics could offer new treatment strategies for cancer patients.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:57Targeted Cancer Therapies
02:04Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
02:56Treatment Resistant Cancers
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...