PARP target practice
Swedish researchers have used an in vitro screen to evaluate the target selectivity of a panel of small molecule poly(ADP-ribose) polymerase inhibitors.1 The findings could eventually lead to next-generation compounds with a better therapeutic index than those now in the clinic for cancer.
The 17 human poly(ADP-ribose) polymerase (PARP) enzymes attach poly-ADP-ribose or mono-ADP-ribose to target proteins. The best-characterized PARP family members are the DNA repair enzymes PARP1 and PARP2. The tankyrases, TNSK1 and TNKS2, are members of the PARP family that are involved in the DNA damage response as well as regulation of wingless-type MMTV integration site (WNT) signaling. The function of many of the remaining PARP enzymes is poorly understood...