ArticleProceedings of the National Academy of Sciences of the United States of America2025
Discovery of an LSD1 PROTAC degrader.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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
7 citing papers in PubMed.
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- An antibody-PROTAC conjugate targets BRD4/c-Myc/PD-L1 to enhance immunotherapy efficacy in triple-negative breast cancer.Cell reports. Medicine · 2026Article
- Comparative analysis for optimal LSD1 inhibitors evaluation techniques: pros and cons.Journal of pharmaceutical analysis · 2026Review
- Prospects and advances of PROTAC in the treatment of hematologic malignancies.Experimental hematology & oncology · 2026Review
- Therapeutic advances in acute myeloid leukemia: from LSD1 blockade to PROTAC-based strategies.Annals of medicine and surgery (2012) · 2026Article
- Discovery of dCDK9-202 as a Highly Potent and Selective PROTAC CDK9 Degrader with StrongJournal of medicinal chemistry · 2025Article
- Discovery of LD-110 as an Effective LSD1 PROTAC Degrader for the Treatment of Esophagus Squamous Cancer.Journal of medicinal chemistry · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Aberrant expression of lysine-specific demethylase 1 (LSD1) has been implicated in various cancers, including acute myeloid leukemia (AML). Recent studies have revealed both catalytic and noncatalytic oncogenic functions of LSD1, which cannot be effectively addressed by traditional small-molecule inhibitors. Therefore, to remove LSD1 and mitigate its oncogenic activity, we utilized the proteolysis-targeting chimera (PROTAC) approach and developed an LSD1 PROTAC degrader MS9117, which recruits the E3 ligase cereblon (CRBN). MS9117 induces LSD1 degradation in a concentration-, time-, CRBN-, and proteasome-dependent manner. Importantly, MS9117 effectively degrades LSD1 and demonstrates superior antiproliferative effects in AML cells, compared to the existing pharmacological LSD1 inhibitors. Furthermore, MS9117 also sensitized nonacute promyelocytic leukemia AML cells to all-trans retinoic acid treatment. Moreover, we developed two negative controls of MS9117, MS9117N1 and MS9117N2, which do not degrade LSD1 or inhibit leukemia cell growth, further confirming the mechanism of action of MS9117. Overall, MS9117 serves as a valuable chemical tool and a potential therapeutic to target both the catalytic and scaffolding functions of LSD1. With several LSD1 inhibitors already in clinical development, the LSD1 degraders such as MS9117 offer an additional option for future clinical studies.
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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.