4L6S

PARP complexed with benzo[1,4]oxazin-3-one inhibitor

Summary for 4L6S

• Entry DOI: 10.2210/pdb4l6s/pdb
• Descriptor: Poly [ADP-ribose] polymerase 1, (2S)-6-{[4-(4-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl]methyl}-2-methyl-2H-1,4-benzoxazin-3(4H)-one (3 entities in total)
• Functional Keywords: dna single-strand break repair sensitize tumors, dna repair enzyme, drd, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : P09874
• Total number of polymer chains: 2
• Total formula weight: 79728.10

Authors

Dougan, D.R.,Mol, C.D.,Lawson, J.D. (deposition date: 2013-06-12, release date: 2013-08-07, Last modification date: 2024-02-28)

Primary citation

Gangloff, A.R.,Brown, J.,de Jong, R.,Dougan, D.R.,Grimshaw, C.E.,Hixon, M.,Jennings, A.,Kamran, R.,Kiryanov, A.,O'Connell, S.,Taylor, E.,Vu, P.
Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors
Bioorg.Med.Chem.Lett., 23:4501-4505, 2013

PubMed Abstract: Structure based drug design of a series of novel 1,4-benzoxazin-3-one derived PARP-1 inhibitors are described. The synthesis, enzymatic & cellular activities and pharmacodynamic effects are described. Optimized analogs demonstrated inhibition of poly-ADP-ribosylation in SW620 tumor bearing nude mice through 24h following a single dose.

PubMed: 23850199
DOI: 10.1016/j.bmcl.2013.06.055

Experimental method

X-RAY DIFFRACTION (2.2 Å)