RGNCY-0099 (6-MOIPP microtubule inhibitor)

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6-MOIPP is a novel indole-based chalcone that disrupts microtubules and induces cell death in glioblastoma.  6-MOIPP targets the colchicine site on β-tubulin and induces mitotic arrest, caspase activation and loss of cell viability.  6-MOIPP impacts the viability of multiple glioblastoma, lung carcinoma and melanoma cell lines but does not affect the viability of normal cell lines at the same concentration (1 µM).  Pharmacokinetic studies in mice have also shown that the concentration of 6-MOIPP in the brain are the same as in the plasma demonstrating that 6-MOIPP penetrates the blood-brain barrier.  Furthermore, 6-MOIPP is effective in suppressing the growth of subcutaneous and intracranial tumor growth of human U251 glioblastoma in xenograft models without displaying toxicity.  6-MOIPP is a potential therapy for the treatment of primary and metastatic brain tumors.

Systematic Name:  (E)-3-(6-methoxy-2-methyl-1H-indol-3-yl)-1-(pyridin-4-yl)prop-2-en-1-one

SMILES: COC1=CC=C2C(NC(C)=C2/C=C/C(C3=CC=NC=C3)=O)=C1

Formula:  C18H16N2O2

Mol Wt:  292.34

PMID:  30426158