LSD1 inhibitor, TAS1440, disrupts INSM1-LSD1 complex activating tumor-suppressive pathways via transcriptional reprogramming in neuroendocrine SCLC - PubMed
5 hours ago
- #LSD1 inhibitor
- #epigenetic therapy
- #SCLC
- TAS1440 is a novel LSD1 inhibitor developed for treating neuroendocrine small cell lung cancer (SCLC).
- TAS1440 disrupts the INSM1-LSD1 complex, leading to activation of tumor-suppressive pathways like NOTCH/TGF-β signaling.
- Unlike irreversible LSD1 inhibitors, TAS1440 non-covalently targets the H3-binding pocket, improving specificity and reducing off-target effects.
- TAS1440 showed efficacy in suppressing SCLC-A cell proliferation and inducing tumor regression in xenograft models.
- The drug works by inhibiting LSD1 activity and remodeling histone marks, activating transcription factors INSM1 and SMAD2.
- Loss of LSD1 enzymatic activity or INSM1 knockout negates TAS1440's effects, defining its mechanism and resistance pathways.
- TAS1440 is a promising next-generation epigenetic therapy for INSM1-high SCLC-A.