Related Experiment Video
Updated: Jun 11, 2026
Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
Published on: June 17, 2022
Dual SYK-HDAC Inhibitor Elicits Striking Efficacy against Acute Myeloid Leukemia: Rational Design, Synthesis, and
Anshul Mishra1, Wen-Bin Yang2,3, Tsu-Shao Liu1
1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110031, Taiwan.
None:
An integrated transcriptomic and survival analysis led to the identification of SYK and HDAC isoforms as age- and FLT3-dependent prognostic markers in acute myeloid leukemia (AML). Driven by the aforementioned, our research group employed a classical ligand-based hybrid pharmacophore strategy to furnish dual-target hybrid frameworks. Antitumor profiling culminated in a tractable bifunctional agent (Compound 14, dual SYK-HDAC inhibitor) endowed with substantial cell growth inhibitory effects against MV4-11 cell lines (AML cell lines harboring FLT3-ITD mutations). Compound 14 downregulated the expression levels of p-SYK and modulated the expression levels of the biomarkers associated with intracellular HDAC inhibition. Transcriptomic profiling revealed significantly suppressed lipid-associated metabolic pathways with Compound 14 treatment. Moreover, Compound 14 demonstrated an impressive pharmacokinetic profile and exerted significant antitumor efficacy in the FLT3-ITD-positive AML xenograft mouse model (approximately 80% decrease in tumor mass). Also, biochemical blood analysis and histopathological studies revealed that Compound 14 demonstrated a good safety profile.
