Evidence map›Paper›PMID 40801664›Full record

ArticleJournal of medicinal chemistry2025

Profiling and Optimizing Targeted Covalent Inhibitors through EGFR-Guided Studies.

Tahereh Damghani, Surbhi P Chitnis, Omobolanle A Abidakun, Kishan B Patel, Kaly S Lin, Emily A Ouellette, Abigail M Lantry, David E Heppner

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Tahereh DamghaniDepartment of Chemistry, The State University of New York at Buffalo, Buffalo, New York 14260, United States.
Surbhi P ChitnisDepartment of Chemistry, The State University of New York at Buffalo, Buffalo, New York 14260, United States.ORCID 0000-0002-5050-2338
Omobolanle A AbidakunDepartment of Chemistry, The State University of New York at Buffalo, Buffalo, New York 14260, United States.ORCID 0000-0002-2009-947X
Kishan B PatelDepartment of Chemistry, The State University of New York at Buffalo, Buffalo, New York 14260, United States.
Kaly S LinDepartment of Chemistry, The State University of New York at Buffalo, Buffalo, New York 14260, United States.
Emily A OuelletteDepartment of Chemistry, The State University of New York at Buffalo, Buffalo, New York 14260, United States.
Abigail M LantryDepartment of Chemistry, The State University of New York at Buffalo, Buffalo, New York 14260, United States.
David E HeppnerDepartment of Chemistry, The State University of New York at Buffalo, Buffalo, New York 14260, United States.ORCID 0000-0002-0722-5160

Funding

X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Vivian Stojanoff · 2019 to 2026
$38.6M
University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8M
Improving Drug Development Through Studies of Protein Kinase InhibitorsR35GM155353 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI David E. Heppner · 2024 to 2026
$1.2M
NCATS NIH HHS UL1 TR001412NIGMS NIH HHS P30 GM133893NIGMS NIH HHS R35 GM155353
6 · The paper itself

Abstract

Targeted covalent inhibitors (TCIs) are actively pursued in drug discovery due to their prolonged target engagement and clinical efficacy. Although kinetic parameters provide a path to their optimization, systematic design strategies and practical guidance remain underexplored. In this study, the EGFR kinase is deployed as a model system to elucidate structural and functional determinants critical for directing the optimization of irreversible TCIs. Functional analyses reveal a two-phase optimization process, underscoring the importance of balancing─rather than maximizing─the inactivation efficiency rate (

Indexed as

ErbB ReceptorsProtein Kinase InhibitorsHumansHydrophobic and Hydrophilic InteractionsKineticsModels, MolecularMutationStructure-Activity RelationshipEGFR protein, humanErbB ReceptorsProtein Kinase Inhibitors

Identifiers

PMID40801664
PMCPMC12400582

What OpenQuestion holds

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Registered trials

None linked

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.