RGNCY-0051 (DDRI-9 DNA damage response inhibitor)

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DDRI-9 is a DNA damage response inhibitor that inhibits phosphorylated histone variant H2AX foci formation upon DNA damage.  It also enhances the cytotoxicity of etoposide and ionizing radiation.  DDRI-9 reduces the foci formation of DNA repair-related proteins including the protein kinase ataxia-telangiectasia mutated, DNA-dependent protein kinase, breast cancer type 1 susceptibility protein and p53-binding protein 1 but not the mediator of DNA damage checkpoint protein 1.  DDRI-9 blocks mitotic progression and the accumulation of mitotic protein and induces cell death by apoptosis.  This suggests that DDRI-9 may be a lead molecule for the development of more enhanced anti-cancer drugs. 

Systematic Name: N-(7-(4-fluorobenzyl)-3-methyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)methanimine oxide

SMILES: O=C1C2=C(N=C([N+]([O-])=C)N2CC3=CC=C(F)C=C3)N(C)C(N1)=O

Formula: C14H12FN5O3

Mol Wt: 317.28

PMID: 26848527