Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State
Nat Commun. 2026 Feb 12;17(1):1214. doi: 10.1038/s41467-026-68909-z.
Yusuke Tsutsui 1 ,
Atsushi Masui 1 ,
Satoshi Konishi 1 ,
Taro Tsujimura 2 ,
Mio Iwasaki 1 ,
Takuya Yamamoto 1 2 3 ,
Shimpei Gotoh 4
Affiliations
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Affiliations
1 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.2 Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.3 Medical-risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan.4 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan. gotoh.shimpei.5m@cira.kyoto-u.ac.jp.
Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by progressive scarring of lung tissue with an urgent need for effective treatments. Studies have shown that the alveolar transitional cell state (ATCS) emerges in fibrotic regions of the IPF lung. However, whether ATCS is the cause or consequence of fibrosis is controversial, and no therapeutic agents targeting the alveolar epithelial differentiation are used to treat IPF. In this study, we performed a drug screening with an in vitro pulmonary fibrosis model using fibroblast-dependent alveolar organoids derived from human induced pluripotent stem cells (iPSCs) and identified p300/CBP inhibitors as candidate therapeutic agents. Multi-omics technology revealed that ATCS induced from human iPSCs-derived alveolar organoids had a compatible profile with that reported in IPF and p300/CBP inhibitors suppressed the emergence of ATCS. Overall, these results elucidate the biological mechanisms of pulmonary fibrosis and provide a potential therapeutic target.
Products
Cat. No.
Product Name
Description
Target
Research Area
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HY-50856
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HY-13030
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HY-13428
HDAC6抑制剂
HY-19615
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HY-112433
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HY-114490
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HY-108463
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99.60%, PROTAC MDM2 蛋白降解剂
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HY-100519
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HY-18627A
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HY-50868
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HY-103020
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HY-115470
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HY-13253
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HY-14414
99.87%, Rev-erbα激动剂
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99.94%, GPR68正变构调节剂
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HY-14715B
98.55%, CHK2 抑制剂
HY-12325
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99.96%, HIF-2α拮抗剂
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98.97%, KRAS-SOS1 Interaction 抑制剂
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99.38%, FAS 抑制剂
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HY-124634
99.68%, PANK Modulator
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HY-100352
98.73%, BRD9/BRD7溴结构域抑制剂
HY-19546
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HY-12345
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99.96%, MAGL抑制剂
HY-19541
98.20%, CBP/p300 溴结构域抑制剂
HY-11999
99.39%, Btk抑制剂
HY-80002
99.04%, BMX抑制剂
HY-18986
98.84%, MDM2-p53抑制剂
HY-15270
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HY-14174
99.0%, γ-Secretase抑制剂
HY-14674
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HY-12828
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HY-10411
JAK2抑制剂
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HY-15738
99.95%, Bcr-Abl抑制剂
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HY-12518
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HY-125751
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HY-119257
Farnesyltransferase 抑制剂
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HY-133083
99.75%, c-Met 抑制剂
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98.80%, γ-secretase调节剂
