RGNCY-0081 (WW437 HDACs-EphA2 inhibitor)

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WW437 is a novel histone deacetylase inhibitor (HDACi) with potent ant-breast cancer activity in vitro and in vivio.  WW437 inhibits phosphorylated EphA2 and EphA2 expression and also blocks HDACs-EphA2 signalling axis in breast cancer. WW437 inhibits 4T1 tumor growth an metastasis in a pre-clinical models.  The combined use of WW437 and an EphA2 inhibitor (ALW-II-41-27) results in a significant reduction in cell viability, greater than observed with either drug alone.  The inhibition of the HDACs-EphA2 signalling axis by WW437 may be a promising target for therapy in advanced breast cancer when used alone or in combination with other therapies.  WW437 inhibition of breast cancer cells has an IC50 of 0.2 µM to 0.5 µM.

Systematic Name: N1-hydroxy-N7-(4-methoxyphenyl)-N7-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)heptanediamide

SMILES:  COC(C=C1)=CC=C1N(C(CCCCCC(NO)=O)=O)CC(N=N2)=CN2C3=CC=CC=C3

Formula: C23H27N5O4

Mol Wt:  437.21

PMID:  29759486