pADPr Inhibitors

Poly(ADP-ribose) polymerase inhibitors, often abbreviated as pADPr inhibitors, belong to a chemical class of compounds designed to target and modulate the activity of poly(ADP-ribose) polymerase (PARP) enzymes. These enzymes play a crucial role in various cellular processes, particularly in the maintenance of genomic integrity and the repair of DNA damage. PARP enzymes catalyze the synthesis of poly(ADP-ribose) chains from NAD+ molecules in response to DNA damage, serving as a signal for DNA repair machinery recruitment. pADPr inhibitors are synthetic molecules designed to interfere with this PARP activity, thus disrupting the DNA repair process. They typically bind to the catalytic domain of PARP enzymes and block their ability to form poly(ADP-ribose) chains, thereby hindering the repair of DNA lesions.

The rationale behind developing pADPr inhibitors lies in their use as research tools for studying DNA repair mechanisms and in the context of certain diseases, such as cancer. By inhibiting PARP activity, these compounds can induce synthetic lethality in cancer cells with defective DNA repair pathways, making them a subject of interest in cancer research. Additionally, pADPr inhibitors have been explored in combination with other DNA-damaging agents to enhance the sensitivity of cancer cells to chemotherapy or radiation therapy. These inhibitors have gained significant attention in recent years, leading to the development of various generations of compounds with improved selectivity and potency, making them valuable tools for dissecting the intricacies of DNA repair.