RGNCY-0095 (NCO-141 SIRT2 inhibitor)

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NCO-141 is a novel specific inhibitor of SIRT2.  It inhibited cell growth of leukemic cell lines including HTLV-1-transformed T-cells .  NCO-141 induced apoptosis by caspase activation and mitochondrial superoxide generation in leukemic cell lines which was not prevented by a caspase inhibitor. NCO-141 increased the LC3-II level with autophagosome accumulation suggesting autophagic cell death.  Therefore,NCO-141 caused apoptosis and autophagy simultaneously.  These data suggest that NCO-141 is highly effective against leukemic cells in caspase-dependent or -independent manners via autophagy and may have therapeutic potential for leukemias such as ALL.  IC50 = 0.5µM

SMILE:  NC(C1=CC=CC=C1NC2=CC=CC(OCCC3=CC=CC(F)=C3)=C2)=C

Systematic Name:   2-(1-aminovinyl)-N-(3-(3-fluorophenethoxy)phenyl)aniline

Molecular Weight:  348.42

Formula:  C22H21FN2O

PMID:  30081901