4- Amino-l,8-naphthalimide

Figure 11.4. PARP inhibitors nicotinamide, 5-methylnicotinamide,6-aminonicotinamide,picolin-amide, 3-methoxybenzamide, benzamide, 3-aminobenzamide, 2-aminobenzamide, 4-aminobenz-amide, coumarin, 3,4-dihydro-5-methylisoquinolinone (PD 1287631, 4-amino-l,8-naphthalimide, 8-hydroxy-2-methyl-3-hydroquina2olin-4-one, phenanthridinone, and 3-0-allQ lbenzamides. This figure is redrawn from Ref 33 and is used with permission.

The effect of PARP inhibitors on the survival of cells exposed to short pulses of ionising radiation separated by a short time interval (1-60 seconds) has been investigated. Cell survival fluctuated with the duration of the interval between doses of radiation. PARP-T cells did not exhibit this osdilatory response and it was hugely abolished in PARP proficient cells by 3AB (10 mM), 4-amino-l, 8-naphthalimide (30 pM) and2-nitro-6[5H]phenanthridlnone (100 pM) (Fig. 3). In contrast, the DNA-PK inhibitor, wortmannin, did not affect the oscillatory response, su esting that PARP, but not DNA-PK, plays a major role in the early radiation response. These authors proposed that the rapid poly(ADP-ribosylation) of ta et proteins, or... 

---