Evidence map›Paper›PMID 41684669›Full record

ArticleACS medicinal chemistry letters2026

Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting.

Tahereh Damghani, Shenghan Song, Kaly S Lin, Jianing Li, David E Heppner

Abstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2026. 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

5 authors.

Tahereh DamghaniDepartment of Chemistry, College of Arts and Sciences, The State University of New York at Buffalo, Buffalo, New York 14260, United States.
Shenghan SongBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, United States.
Kaly S LinDepartment of Chemistry, College of Arts and Sciences, The State University of New York at Buffalo, Buffalo, New York 14260, United States.
Jianing LiBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, United States.ORCID 0000-0002-0143-8894
David E HeppnerDepartment of Chemistry, College of Arts and Sciences, 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
Structure, Mechanism, and Regulation of PACAP/VIP GPCR SubtypesR01GM129431 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI LI, JIANING · 2018 to 2022
$1.7M
Precision Design of Antimicrobial Peptides Against Bacterial InfectionsR01GM143370 · NIGMS · PURDUE UNIVERSITY · PI LI, JIANING · 2022 to 2025
$1.2M
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 R01 GM129431NIGMS NIH HHS R01 GM143370NIGMS NIH HHS R35 GM155353
6 · The paper itself

Abstract

Inhibitors targeting mutant EGFR remain a persistent need in combating drug resistance in non-small cell lung cancer. To better understand the molecular factors involved in targeting T790M and C797S mutations, we determined X-ray cocrystal structures of fourth-generation inhibitors BI-8128 and BI-4732. Analysis from molecular dynamics and thermodynamic integration calculations correlated with biochemical and cellular measurements indicate that BI-8128 binds the double T790M/C797S more strongly than the single mutations individually. This observation showcases strengths in the design of these fourth-generation EGFR inhibitors as profile criteria require drugs to inhibit an array of oncogenic and drug resistance mutations.

Indexed as

crystallographyEGFRkinase inhibitorsmolecular dynamicsnon-small cell lung cancerstructural biologytargeted therapy

Identifiers

PMID41684669
PMCPMC12893389

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.