RGNCY-0082 (Compound 13 Methuosis inducer)

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Methuosis is a novel non-apoptotic mechanism of cell death that is characterized by cytoplasmic vacuole accumulation.  Compound 13 is a novel potent vacuole-inducer and displayed differential toxicities across a broad range of cancer cell lines (including MCF-7, MDA-MB-231, HCT116 and A375) but had no effect on the non-tumorigenc epithelial cell line, MCF-10A.  Compound 13 was demonstrated to cause cell death via methuosis. Compound 13 did not demonstrate any side effects despite significant pharmacological efficacy in the suppression of MDA-MB-231 tumor growth in a xenograft mouse model.  Compound 13 is the first methuosis inducer with efficacy in vivo and shows therapeutic potential in targeting methuosis in cancer treatment. A375 IC50 = 0.326+0.026µM , MDA-MB-231 IC50 = 1.571+0.066µM , MCF7 IC50 = 2.611+0.739µM , HCT116 IC50 = 1.008+0.042µM .



Systematic Name: N-(4-methyl-3-((6-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)methyl)phenyl)-3-(trifluoromethyl)benzamide

SMILES: O=C(NC1=CC=C(C)C(CC2=C(C=CN3)C3=NC(C4=CC=CN=C4)=C2)=C1)
C5=CC=CC(C(F)(F)F)=C5
Formula: C28H21F3N4O
Mol Wt:  486.17

PMID: 29878764



Tags: Cancer, small molecule, breast cancer, MCF-7, MDA-MB-231, MCF-10A, RGNCY-0082, Compound 13, methuosis, HCT116, A375