RGNCY-0094 (S130 ATG4B inhibitor)

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S130 is a potent and specific inhibitor of ATG4B and not other proteases.  S130 may attenuate the delipidation of LC3-II on the autolysosomes to suppress LC3-II recycling that usually occurs following LC3-II cleavage by ATG4B.  S130 induced cell death in cancer cells which was accompanied with autophagy stress and could be further exacerbated by nutrient deprivation.  This cytotoxicity could be partially reversed by enhancing ATG4B activity.  S130 was further shown to be distributed in tumor tissues in vivo and was effective in arresting the growth of colorectal cancer cells. Hela (IC50 = 16.1µM) and HCT116 (IC50 = 9.0µM). 

SMILE:  O=C1C2=CC=CC=C2C3=C4C1=NC=C(C(NCCCN(CC)CC)=O)C4=CC=C3

Systematic Name:   N-(3-(diethylamino)propyl)-7-oxo-7H-dibenzo[de,g]quinoline-4-carboxamide

Molecular Weight:  387.48

Formula:  C24H25N3O2

PMID:  30176161