Evidence map›Paper›PMID 41881985›Full record

ArticleNature communications2026

LSD1 inhibitor, TAS1440, disrupts INSM1-LSD1 complex activating tumor-suppressive pathways via transcriptional reprogramming in neuroendocrine SCLC.

Takumitsu Machida, Yingbo Gong, Sayaka Tsukioka, Atsushi Onodera, Akitoshi Nakayama, Naoko Hashimoto, Takahiro Fuchigami, Motoi Nishimura, Tomohiro Ogino, Ryota Kurimoto and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
    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

28 authors.

Takumitsu Machida *Discovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan.ORCID http://orcid.org/0009-0006-8806-363X
Yingbo Gong *Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.ORCID http://orcid.org/0000-0002-1897-0625
Sayaka TsukiokaDiscovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan.
Atsushi OnoderaResearch Institute of Disaster Medicine (RIDM), Chiba University, Chiba, Japan.
Akitoshi NakayamaDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Naoko HashimotoDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Takahiro FuchigamiDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.ORCID http://orcid.org/0000-0002-6946-1345
Motoi NishimuraDivision of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba, Japan.
Tomohiro OginoResearch Institute of Disaster Medicine (RIDM), Chiba University, Chiba, Japan.
Ryota KurimotoDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Yasufumi UematsuDepartment of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hidemi SuzukiDepartment of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hongye YuDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Mingyang ChenDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Masataka YokoyamaDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Ikki SakumaDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Yuki TakiDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Takashi KonoDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Takashi MikiDepartment of Medical Physiology, Graduate School of Medicine, Chiba University, Chiba, Japan.ORCID http://orcid.org/0000-0001-5741-1626
Shinichiro MotohashiDepartment of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.ORCID http://orcid.org/0000-0002-9332-3129
Yusuke KawashimaDepartment of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Japan.ORCID http://orcid.org/0000-0002-9779-8199
Osamu OharaDepartment of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Japan.ORCID http://orcid.org/0000-0002-3328-9571
Satoshi YamashitaDiscovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan.ORCID http://orcid.org/0000-0001-9876-2465
Tatsuya SuzukiDiscovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan.
Ryo HatanakaDiscovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan.ORCID http://orcid.org/0000-0002-2879-1524
Yasuo KodamaDiscovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan.ORCID http://orcid.org/0000-0001-9694-8688
Shuichi OhkuboDiscovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan. s-ohkubo@taiho.co.jp.ORCID http://orcid.org/0000-0001-9554-4534
Tomoaki TanakaDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan. tomoaki@restaff.chiba-u.jp.ORCID http://orcid.org/0000-0002-9761-1750

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) 23K17429MEXT | Japan Society for the Promotion of Science (JSPS) 25K10723
6 · The paper itself

Abstract

Small cell lung cancer (SCLC) is aggressive with limited treatment options, requiring new therapies. Lysine-specific histone demethylase 1 A (LSD1) maintains neuroendocrine state by repressing NOTCH/TGF-β signaling; their reactivation suppresses proliferation and induces differentiation. However, mechanisms of LSD1 inhibition and chemoresistance remain unclear. Here we developed TAS1440, a histone H3-competitive LSD1 inhibitor, using structure-based engineering to improve specificity and reduce off-target effects. Unlike irreversible inhibitors targeting the flavin adenine dinucleotide site, TAS1440 non-covalently targets the H3-binding pocket to enhance safety and efficacy. TAS1440 suppressed proliferation in INSM1/ASCL1-high SCLC-A cells and induced tumor regression in xenografts. TAS1440 acts through dual mechanisms: inhibiting LSD1 activity and disrupting LSD1-repressive complexes, remodeling histone marks and activating transcription factors INSM1 and SMAD2. These actions reprogram tumor-suppressive TGF-β/NOTCH signaling, supporting TAS1440 as epigenetic therapy for SCLC. Loss of LSD1 enzymatic activity or INSM1 knockout abrogated TAS1440 effects, defining its mode of action and chemoresistance. These findings support TAS1440 as a next-generation epigenetic therapy candidate for INSM1-high SCLC-A.

Indexed as

Histone DemethylasesLung NeoplasmsSmall Cell Lung CarcinomaAnimalsBasic Helix-Loop-Helix ProteinsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHistonesHumansMiceReceptors, NotchSignal TransductionTransforming Growth Factor betaXenograft Model Antitumor AssaysASCL1 protein, humanBasic Helix-Loop-Helix ProteinsHistone DemethylasesHistonesKDM1A protein, humanReceptors, NotchTransforming Growth Factor beta

Identifiers

PMID41881985
PMCPMC13181136

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Registered trials

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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.