2024
DOI: 10.3389/fphar.2024.1335246
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Epigenetic small-molecule screen for inhibition and reversal of acinar ductal metaplasia in mouse pancreatic organoids

Kalina R. Atanasova,
Corey M. Perkins,
Ranjala Ratnayake
et al.

Abstract: Background: Acinar ductal metaplasia (ADM) is among the earliest initiating events in pancreatic ductal adenocarcinoma (PDAC) development.Methods: We developed a novel morphology-based screen using organoids from wildtype and p48Cre/+ (Cre) mice to discover epigenetic modulators that inhibit or reverse pancreatic ADM more effectively than the broad-spectrum HDAC inhibitor trichostatin A (TSA).Results: Of the 144 compounds screened, nine hits and two additional natural product HDAC inhibitors were validated by … Show more

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Cited by 4 publications
(1 citation statement)
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“…and Atanasova et al. demonstrated the effect of small molecules in mouse pancreatic acinar that causes inhibition or reversal of acinar-to-acinar ductal metaplasia (ADM) using high-content image-based screening in organoid culture [ 128 , 129 ]. Advances in technology in organoid culture and the remarkable self-organizing properties reflecting key structural and functional attributes of organs such as brain, kidney, lung, gut, or similar even hold promise to predict drug response in a personalized fashion.…”
Section: Novel Applications Of Morphological Profiling In Drug Discoverymentioning
confidence: 99%
“…and Atanasova et al. demonstrated the effect of small molecules in mouse pancreatic acinar that causes inhibition or reversal of acinar-to-acinar ductal metaplasia (ADM) using high-content image-based screening in organoid culture [ 128 , 129 ]. Advances in technology in organoid culture and the remarkable self-organizing properties reflecting key structural and functional attributes of organs such as brain, kidney, lung, gut, or similar even hold promise to predict drug response in a personalized fashion.…”
Section: Novel Applications Of Morphological Profiling In Drug Discoverymentioning
confidence: 99%