Evidence map›Paper›PMID 42864505›Full record

ArticleThe AAPS journal2026

Liquid Chromatography/tandem Mass Spectrometry-based Target Engagement of Lysine-specific Demethylase 1 Inhibitor TAK-418 Through Detecting Covalent Adducts in the Brain.

Kota Matsumiya, Shinji Iwasaki, Satoru Matsuda, Yohei Kosugi, Hisao Shimizu, Masaaki Kakehi, Rina Baba, Nobuyuki Amano, Atsushi Nakatani, Haruhide Kimura and 1 more

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Article in The AAPS journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Kota MatsumiyaDrug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa, 251-8555, Japan. kouta.matsumiya@takeda.com.ORCID http://orcid.org/0009-0007-2818-4621
Shinji IwasakiDrug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa, 251-8555, Japan.ORCID http://orcid.org/0000-0001-5339-8372
Satoru MatsudaNeuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited, Fujisawa, Japan.ORCID http://orcid.org/0000-0001-7538-6962
Yohei KosugiDrug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa, 251-8555, Japan.ORCID http://orcid.org/0000-0001-9318-4723
Hisao ShimizuDrug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa, 251-8555, Japan.ORCID http://orcid.org/0000-0003-1401-7041
Masaaki KakehiDrug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa, 251-8555, Japan.ORCID http://orcid.org/0000-0002-6057-0596
Rina BabaNeuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited, Fujisawa, Japan.ORCID http://orcid.org/0000-0001-8855-454X
Nobuyuki AmanoDrug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa, 251-8555, Japan.ORCID http://orcid.org/0009-0006-8483-2673
Atsushi NakataniNeuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited, Fujisawa, Japan.ORCID http://orcid.org/0000-0003-0303-3177
Haruhide KimuraNeuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited, Fujisawa, Japan.ORCID http://orcid.org/0000-0002-8292-3647
Hideki HirabayashiDrug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa, 251-8555, Japan.ORCID http://orcid.org/0000-0002-6812-3651

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Translating pharmacokinetics (PK) and pharmacodynamics (PD) from preclinical to clinical is important in successful development of drugs for central nervous system (CNS) diseases. TAK-418 is a clinical candidate of lysine-specific demethylase 1 (LSD1) inhibitor with a unique mechanism of action; it covalently binds to flavin adenine dinucleotide (FAD) to form a compact adduct formylated FAD (F-FAD), thereby minimizing hematological side effect risks. In this study, we established a liquid chromatography-tandem mass spectrometry (LC/MS/MS)-based approach for evaluating F-FAD as a target engagement marker for TAK-418 to advance PK/PD translation and clinical dose setting. In rats, LC/MS/MS enabled detection of TAK-418-induced F-FAD formation in the brain with chromatographic separation from native FAD. F-FAD levels were positively associated with LSD1 protein abundance across brain regions and increased with increasing TAK-418 dose. LSD1 occupancy calculated from F-FAD concentrations was correlated with the inhibition level of LSD1 enzyme activity in rat hippocampus. This mechanism-based approach provides a link between covalent adduct formation, target engagement, and enzyme inhibition in the brain. In addition, similar point estimates of the half-maximal effective concentration (EC

Indexed as

BrainEnzyme InhibitorsHistone DemethylasesLiquid Chromatography-Mass SpectrometryTandem Mass SpectrometryAnimalsChromatography, LiquidHumansMaleRatsRats, Sprague-DawleyThiophenesEnzyme InhibitorsHistone DemethylasesKDM1A protein, ratTAK-418ThiophenesF-FADLC/MS/MSLSD1Pharmacokinetics/pharmacodynamicsTarget engagement

Identifiers

PMID42864505

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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.