ArticleACS central science2024
Molecular Bidents with Two Electrophilic Warheads as a New Pharmacological Modality.
Article in ACS central science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed.
- Towards better outcomes for epidermal growth factor receptor L858R+ lung cancer patients: mutant-selective allosteric inhibitors and the potential for double-drugging.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- Design and development of novel EGFR inhibitors spanning all subgroups of EGFR mutations in non-small cell lung cancer.Innovation (Cambridge (Mass.)) · 2026Article
- Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Covalent Alkynylpyridopyrimidinones Targeting Cysteine 775 of the Epidermal Growth Factor Receptor Overcome Resistance to Current Therapies.Journal of medicinal chemistry · 2026Article
- Targeted NAT10 Degradation by PROTAC NP1192 Suppresses Hypoxia-Adaptive Glycolysis and Reinvigorates CD8ACS central science · 2025Article
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Exploring Extended Warheads toward Developing Cysteine-Targeted Covalent Kinase Inhibitors.Journal of chemical information and modeling · 2024Article
- Open-source electrophilic fragment screening platform to identify chemical starting points for UCHL1 covalent inhibitors.SLAS discovery : advancing life sciences R & D · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
A systematic strategy to develop dual-warhead inhibitors is introduced to circumvent the limitations of conventional covalent inhibitors such as vulnerability to mutations of the corresponding nucleophilic residue. Currently, all FDA-approved covalent small molecules feature one electrophile, leaving open a facile route to acquired resistance. We conducted a systematic analysis of human proteins in the protein data bank to reveal ∼400 unique targets amendable to dual covalent inhibitors, which we term "molecular bidents". We demonstrated this strategy by targeting two kinases: MKK7 and EGFR. The designed compounds, ZNL-8162 and ZNL-0056, are ATP-competitive inhibitors that form two covalent bonds with cysteines and retain potency against single cysteine mutants. Therefore, molecular bidents represent a new pharmacological modality with the potential for improved selectivity, potency, and drug resistance profile.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.