Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 617

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors

Open access
Singh, Anju, Venkannagari, Sreedhar, Oh, Kyu H., Zhang, Ya-Qin, Rohde, Jason M., Liu, Li, Nimmagadda, Sridhar, Sudini, Kuladeep, Brimacombe, Kyle R., Gajghate, Sachin, Ma, Jinfang, Wang, Amy, Xu, Xin, Shahane, Sampada A., Xia, Menghang, Woo, Juhyung, Mensah, George A., Wang, Zhibin, Ferrer, Marc, Gabrielson, Edward, Li, Zhuyin, Rastinejad, Fraydoon, Shen, Min, Boxer, Matthew B., Biswal, Shyam·2016·ACS Chemical Biology
DOI 10.1021/acschembio.6b00651
Open this paper in CoChat — free account

Abstract

Loss of function mutations in Kelch-like ECH Associated Protein 1 (KEAP1), or gain-of-function mutations in nuclear factor erythroid 2-related factor 2 (NRF2), are common in non-small cell lung cancer (NSCLC) and associated with therapeutic resistance. To discover novel NRF2 inhibitors for targeted therapy, we conducted a quantitative high-throughput screen using a diverse set of ∼400 000 small molecules (Molecular Libraries Small Molecule Repository Library, MLSMR) at the National Center for Advancing Translational Sciences. We identified ML385 as a probe molecule that binds to NRF2 and inhibits its downstream target gene expression. Specifically, ML385 binds to Neh1, the Cap 'N' Collar Basic Leucine Zipper (CNC-bZIP) domain of NRF2, and interferes with the binding of the V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homologue G (MAFG)-NRF2 protein complex to regulatory DNA binding sequences. In clonogenic assays, when used in combination with platinum-based drugs, doxorubicin or taxol, ML385 substantially enhances cytotoxicity in NSCLC cells, as compared to single agents. ML385 shows specificity and selectivity for NSCLC cells with KEAP1 mutation, leading to gain of NRF2 function. In preclinical models of NSCLC with gain of NRF2 function, ML385 in combination with carboplatin showed significant antitumor activity. We demonstrate the discovery and validation of ML385 as a novel and specific NRF2 inhibitor and conclude that targeting NRF2 may represent a promising strategy for the treatment of advanced NSCLC.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1021/acschembio.6b00651

Cites

11 of 11 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 11 references

Cited by

See all 617

Metadata

Authors
Singh, A., Venkannagari, S., Oh, K. H., Zhang, Y.-Q., Rohde, J. M., Liu, L., Nimmagadda, S., Sudini, K., Brimacombe, K. R., Gajghate, S., Ma, J., Wang, A., Xu, X., Shahane, S. A., Xia, M., Woo, J., Mensah, G. A., Wang, Z., Ferrer, M., Gabrielson, E., Li, Z., Rastinejad, F., Shen, M., Boxer, M. B., & Biswal, S.
Venue
ACS Chemical Biology
Publisher
American Chemical Society (ACS)
Published
2016-10-17
Volume
11
Issue
11
Pages
3214-3225
ISSN
  • 1554-8929 (ISSN-L)
  • 1554-8937
DOI
10.1021/acschembio.6b00651
OpenAlex
W2515257966
Cited by
617
References
11
FWCI
13.69
Type
journal article
Language
en
Open access
green

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. https://app.cochat.ai/papers/10.1021/acschembio.6b00651
The paper
Singh, A., Venkannagari, S., Oh, K. H., Zhang, Y.-Q., Rohde, J. M., Liu, L., Nimmagadda, S., Sudini, K., Brimacombe, K. R., Gajghate, S., Ma, J., Wang, A., Xu, X., Shahane, S. A., Xia, M., Woo, J., Mensah, G. A., Wang, Z., Ferrer, M., . . . Biswal, S. (2016). Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. ACS Chemical Biology. https://doi.org/10.1021/acschembio.6b00651

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.