Delving into the Latest Updates on FTO inhibitor 8v(Shanghai Institute of Materia Medica) with Synapse

Fat mass obesity-associated protein (FTO) has been emerging as a potential therapeutic target for drug discovery in RNA epigenetics. In this work, a series of novel FTO inhibitors featuring an acylhydrazone scaffold were identified, and the optimized compounds 8t-v showed potent FTO inhibitory activities with IC₅₀ values ranging from 7.1 to 9.4 μM. FTO inhibitor 8t, as the lead compound, exhibited potent antiproliferative capacities against MOLM13, NB4, and THP-1 with IC₅₀ values of 0.35, 0.59, and 0.70 μM, respectively, and remarkably induced NB4 cell apoptosis. Compound 8t also inhibited the FTO demethylation, enhanced the abundance of m⁶A, stabilized FTO protein folding, and regulated the oncogenic FTO signaling pathway. Importantly, compound 8t significantly caused a tumor volume reduction and tumor weight loss with a tumor growth inhibition (TGI) value of 51% in NB4 xenograft mice. Overall, our work provided valuable lead compounds for FTO inhibitors featuring an acylhydrazone scaffold with potent antileukemia activity both in vitro and in vivo.

100 Deals associated with FTO inhibitor 8v(Shanghai Institute of Materia Medica)

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Indication	Highest Phase	Country/Location	Organization	Date
Leukemia	Preclinical	China	University of Chinese Academy of Sciences	17 Jan 2025
Leukemia	Preclinical	China	Shanghai Institute of Materia Medica Chinese Academy of Sci	17 Jan 2025