ArticleAngewandte Chemie (International ed. in English)2024
Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury.
Article in Angewandte Chemie (International ed. in English), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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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.
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.
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Next Generation Hosts for Protein Recognition, Assembly and More.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- AI-assisted identification of innovative phytochemicals from Aizoon canariense aimed at brachyury protein in chordoma: a computational strategy.Scientific reports · 2025Article
- A Metalloporphyrin Nanosystem Enables Non-Invasive Visualization and Specific Treatment for Thrombosis and Ischemic Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma.Science advances · 2025Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Brachyury is an oncogenic transcription factor whose overexpression drives chordoma growth. The downmodulation of brachyury in chordoma cells has demonstrated therapeutic potential, however, as a transcription factor it is classically deemed "undruggable". Given that direct pharmacological intervention against brachyury has proven difficult, attempts at intervention have instead targeted upstream kinases. Recently, afatinib, an FDA-approved kinase inhibitor, has been shown to modulate brachyury levels in multiple chordoma cell lines. Herein, we use afatinib as a lead to undertake a structure-based drug design approach, aided by mass-spectrometry and X-ray crystallography, to develop DHC-156, a small molecule that more selectively binds brachyury and downmodulates it as potently as afatinib. We eliminated kinase-inhibition from this novel scaffold while demonstrating that DHC-156 induces the post-translational downmodulation of brachyury that results in an irreversible impairment of chordoma tumor cell growth. In doing so, we demonstrate the feasibility of direct brachyury modulation, which may further be developed into more potent tool compounds and therapies.
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Registered trials
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.