Poly [ADP-ribose] polymerase 1 (PARP1) (PARP1)

Poly [ADP-ribose] polymerase 1 (PARP1) is a nuclear enzyme essential for DNA damage repair, specifically through the base excision repair (BER) pathway [3, 5]. It functions by detecting DNA single-strand breaks and catalyzing the addition of poly(ADP-ribose) chains to itself and other proteins, which recruits repair factors to the site of injury [3]. PARP1 is a major therapeutic target in oncology due to the principle of synthetic lethality, where its inhibition leads to the death of cancer cells already deficient in other repair pathways, such as those with BRCA1/2 mutations [5, 7]. SNV1521 is a clinical-stage, small-molecule inhibitor that is highly selective for PARP1 over PARP2 [2, 5]. This selectivity is intended to improve the safety profile by reducing the hematological toxicities, such as anemia, that are commonly seen with non-selective first-generation PARP inhibitors [2, 9]. Additionally, SNV1521 is designed to be CNS-penetrant, allowing it to target malignancies within the central nervous system [1, 3]. It also functions as a PARP trapper, creating toxic PARP-DNA complexes that further drive genomic instability in tumor cells [2, 4].

Other names

PARP-1ADPRTADPRT1PPOLARTD1NAD(+) ADP-ribosyltransferase 1

Selective inhibition of PARP1 catalytic activity and PARP trapping on damaged DNA