PARP1 Inhibitor

Olaparib (AZD2281; KU0059436) is a potent and orally active PARP inhibitor with IC₅₀s of 5 and 1 nM for PARP1 and PARP2, respectively. Olaparib is an autophagy and mitophagy activator. Olaparib cannot cross the intact blood-brain barrier (BBB).

XAV-939 is a Tankyrase inhibitor. XAV-939 has inhibitory activity for TNKS1 and TNKS2 with IC₅₀ values of 5 nM and 2 nM, respectively. XAV-939 also is an enhancer of osteoblastic differentiation of hMSCs. XAV-939 can be used for the research of conditions associated with activated Wnt signaling, such as cancer, fibrotic diseases and conditions associated with low bone formation.

Talazoparib (BMN-673) is a highly potent, orally active PARP1/2 inhibitor.Talazoparib inhibits PARP1 and PARP2 enzyme activity with K_is of 1.2 nM and 0.87 nM, respectively. Talazoparib has antitumor activity.

Niraparib (MK-4827) is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with IC₅₀s of 3.8 and 2.1 nM, respectively. Niraparib leads to inhibition of repair of DNA damage, activates apoptosis and shows anti-tumor activity.

Saruparib (AZD5305) is a potent, orally active and selective PARP inhibitor and trapper with IC₅₀ values of 3 nM and 1400 nM for PARP1 and PARP2, respectively. Saruparib has anti-proliferative activity and inhibits growth in cells with deficiencies in DNA repair.

PARP1-IN-56 (Compound RCY) is an I-labeled poly(ADP−ribose) polymerase (PARP1) inhibitor. PARP1-IN-56 can be radiolabeled with ²¹¹At or ¹²⁵I for use as an α-emitting radiotherapeutic agent. PARP1-IN-56 can be used for the research of cancer.

Rucaparib (AG014699) is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a K_i of 1.4 nM for PARP1. Rucaparib is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib has the potential for castration-resistant prostate cancer (CRPC) research.

Veliparib (ABT-888) is a potent PARP inhibitor, inhibiting PARP1 and PARP2 with K_is of 5.2 and 2.9 nM, respectively.

PJ34 is a potent specific inhibitor of PARPl/2 with IC₅₀ of 110 nM and 86 nM, respectively.

IRF1-IN-1 (Compound I-2) is an IRF1 inhibitor. IRF1-IN-1 decreases the recruitment of IRF1 to the promoter of CASP1. IRF1-IN-1 inhibits cell death signaling pathway (i.e., cleavage of Caspase 1, GSDMD, IL-1 and PARP1). IRF1-IN-1 has a protective effect on ionizing radiation-induced inflammatory skin injury.

Fluzoparib (SHR3162) is a potent and orally active PARP1 inhibitor (IC₅₀=1.46±0.72 nM, a cell-free enzymatic assay) with superior antitumor activity. Fluzoparib selectively inhibits the proliferation of homologous recombination repair (HR)-deficient cells, and sensitizes both HR-deficient and HR-proficient cells to cytotoxic agents. Fluzoparib exhibits good pharmacokinetic properties in vivo and can be used for BRCA1/2-mutant relapsed ovarian cancer research.

KSQ-4279 (USP1-IN-1) is a potent USP1 inhibitor and a selective PARP1 inhibitor. KSQ-4279 is promising for research of cancers.

SK-575 is a highly potent and specific proteolysis-targeting chimera (PROTAC) degrader of PARP1, with an IC₅₀ of 2.30 nM. SK-575 potently inhibits the growth of cancer cells bearing BRCA1/2 mutations.

Niraparib hydrochloride (MK-4827 hydrochloride) is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with IC₅₀s of 3.8 and 2.1 nM, respectively. Niraparib hydrochloride leads to inhibition of repair of DNA damage, activates apoptosis and shows anti-tumor activity.

Rucaparib (AG014699) phosphate is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a K_i of 1.4 nM for PARP1. Rucaparib phosphate is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib phosphate has the potential for castration-resistant prostate cancer (CRPC) research.

IRF1-IN-2 (Compound I-19) is an IRF1 inhibitor. IRF1-IN-2 decreases the recruitment of IRF1 to the promoter of CASP1. IRF1-IN-2 inhibits cell death signaling pathway (i.e., cleavage of Caspase 1, GSDMD, IL-1 and PARP1; inhibits the Pho of TKB1, upregulates GPX4 and downregulates FACL4). IRF1-IN-2 has a protective effect on ionizing radiation-induced inflammatory skin injury.

Paris saponin VII (Chonglou Saponin VII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii. Paris saponin VII-induced apoptosis in K562/ADR cells is associated with Akt/MAPK and the inhibition of P-gp. Paris saponin VII attenuates mitochondrial membrane potential, increases the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decreases the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. Paris saponin VII induces a robust autophagy in K562/ADR cells and provides a biochemical basis in the treatment of leukemia.

Niraparib tosylate (MK-4827 tosylate) is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with an IC₅₀ of 3.8 and 2.1 nM, respectively. Niraparib tosylate leads to inhibition of repair of DNA damage, activates apoptosis and shows anti-tumor activity.

AG14361 is a potent PARP-1 inhibitor, with a K_i of < 5 nM, and in permeabilized SW620 and intact SW620 cells, the IC₅₀s are 29 nM and 14 nM, respectively.

Stenoparib (E7449) is a potent PARP1 and PARP2 inhibitor and also inhibits TNKS1 and TNKS2, with IC₅₀s of 2.0, 1.0, ～50 and ～50 nM for PARP1, PARP2, TNKS1 and TNKS2, respectively, using ³²P-NAD⁺ as substrate.