Evidence map›Paper›PMID 37481672›Full record

ArticleScientific reports2023

Targeting Mcl-1 by a small molecule NSC260594 for triple-negative breast cancer therapy.

Shengli Dong, Margarite D Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M Collins-Burow, Matthew E Burow, Suresh K Alahari

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 13% of its field
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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Small molecule Mcl-1 inhibitor for triple negative breast cancer therapy.Frontiers in cell and developmental biology · 2024
    Review
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

7 authors at 3 institutions in 2 countries.

Shengli DongTYK Medicines Inc., Block D, No. 778 Huaxi Avenue, Changxing, 313100, Zhejiang, People's Republic of China. shengli.dong@tykmedicines.com.
Margarite D MatossianTulane University School of Medicine, New Orleans, LA, 70118, USA.
Hassan YousefiDepartment of Biochemistry and Molecular Biology, LSUHSC, CSRB 406, New Orleans, LA, 70112, USA.
Maninder KhoslaDepartment of Biochemistry and Molecular Biology, LSUHSC, CSRB 406, New Orleans, LA, 70112, USA.
Bridgette M Collins-BurowTulane University School of Medicine, New Orleans, LA, 70118, USA.
Matthew E BurowTulane University School of Medicine, New Orleans, LA, 70118, USA.
Suresh K AlahariDepartment of Biochemistry and Molecular Biology, LSUHSC, CSRB 406, New Orleans, LA, 70112, USA. salaha@lsuhsc.edu.
Louisiana State University Health Sciences Center New Orleans · USTulane University · USZhejiang Medicine (China) · CN

Funding

BASIC RESEARCH TRAINING IN MEDICAL ONCOLOGYT32CA009566 · NCI · UNIVERSITY OF CHICAGO · PI OLUFUNMILAYO F. OLOPADE · 1987 to 2026
$10.5M
NCI NIH HHS T32 CA009566
6 · The paper itself

Abstract

Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased apoptosis, which was confirmed by using an Annexin-V/PI assay. Interestingly, NSC260594 treatment reduced the cancer stem cell (CSC) population in TNBCs. To make NSC260594 more clinically relevant, we treated NSC260594 with TNBC cell derived xenograft (CDX) mouse model, and with patient-derived xenograft (PDX) organoids. NSC260594 significantly suppressed MDA-MB-231 tumor growth in vivo, and furthermore, the combination treatment of NSC260594 and everolimus acted synergistically to decrease growth of TNBC PDX organoids. Together, we found that NSC260594 might serve as a lead compound for triple-negative breast cancer therapy through targeting Mcl-1.

Indexed as

Antineoplastic AgentsTriple Negative Breast NeoplasmsAnimalsAnnexin A5AntibodiesBenzamidesDisease Models, AnimalHumansMiceMyeloid Cell Leukemia Sequence 1 ProteinQuinolinesAnnexin A5AntibodiesAntineoplastic AgentsBenzamidesMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinNSC260594Quinolines

Identifiers

PMID37481672
PMCPMC10363135
OpenAlexW4385143961

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.