PARP2 Inhibitor

PARP1/c-Met-IN-3 (Compound L19) is a selective c-Met and PARP1 inhibitor, with an IC₅₀ of 5.4 nM against c-Met and an IC₅₀ of 3.7 nM against PARP1. PARP1/c-Met-IN-3 inhibits PARP2 enzymatic activity with an IC₅₀ of 4.52 nM, and shows no specificity for PARP1 and PARP2. PARP1/c-Met-IN-3 induces cell cycle arrest and apoptosis. PARP1/c-Met-IN-3 exhibits anti-tumor activity against triple-negative breast cancer.

PARP1-IN-44, an Olaparib (HY-10162) derivative, is an orally active PARP1 inhibitor (IC₅₀ = 0.6 nM), and also inhibits PARP2 (IC₅₀ = 1.0 nM) and PARP7 (IC₅₀ = 7.5 nM). PARP1-IN-44 has selective antiproliferative activity against BRCA-deficient cancer cells with minimal toxicity to normal cells. PARP1-IN-44 induces G2/M phase arrest, promotes apoptosis, elevates ROS levels, disrupts mitochondrial membrane potential. PARP1-IN-44 suppresses PARylation while increasing γH2AX accumulation. PARP1-IN-44 activates the cGAS-STING pathway, upregulating IFN-β and CXCL10 expression. PARP1-IN-44 enhancing CD8+ T cell infiltration in a CT26 tumor mouse model, demonstrating robust in vivo antitumor efficacy.

ATR/PARP1-IN-1 is a potent ATR and PARP1 dual inhibitor with IC₅₀s of 17.3 nM and 0.38 nM, respectively. ATR/PARP1-IN-1 effectively reduces cell viability, induces apoptosis and DNA damage. ATR/PARP1-IN-1 significantly impairs triple-negative breast cancer (TNBC) colony formation, migration, and invasion. ATR/PARP1-IN-1 suppresses tumor growth effectively in MDA-MB-468 xenografted mice, with no significant body weight change.

PARP1/EZH2-IN-1 is a selective PARP1 and EZH2 dual inhibitor. PARP1/EZH2-IN-1 has IC₅₀s of 28 nM, 414 nM and 74 nM for PARP1, PARP2 and EZH2, respectively. PARP1/EZH2-IN-1 inhibits the proliferation and migration of TNBC cells (triple-negative breast Cancer cells). PARP1/EZH2-IN-1 induces PANoptosis (Apoptosis, Pyroptosis and Necroptosis), increases the level of reactive oxygen species (ROS), and activates related inflammatory pathways. PARP1/EZH2-IN-1 can be used in triple-negative breast cancer research.

YCH3292, a derivative of YCH189 (HY-155993) is a potent, selective and orally active PARP1/2 inhibitor with IC₅₀ both <0.001 nM. YCH3292 can increase the stability of PARP-DNA complexes. YCH3292 exhibits robust antiproliferative activity. YCH3292 can induce double-strand breaks in DNA, increase the protein levels of γH2AX, P-RPA32, and P-Chk1 and induce tumor cells S or G2/M phase arrest and apoptosis. YCH3292 can inhibit tumor growth in MC38 xenograft model.

PARP-1/2-IN-5 (Compound 12) is a PARP-1/2 inhibitor, with the IC₅₀ values for PARP-1 and PARP-2 being 118 and 11 nM respectively. PARP-1/2-IN-5 can be used for the study of inflammatory diseases and neurodegenerative disorders.

PARP1/CDK12-IN-2 is a selective dual PARP1/CDK12 inhibitor with an IC₅₀ of 42 nM for CDK12 and an IC₅₀ of 35 nM for PARP1. PARP1/CDK12-IN-2 inhibits CDK13. PARP1/CDK12-IN-2 induces Apoptosis and induces G2/M phase arrest. PARP1/CDK12-IN-2 exhibits anticancer activity against breast cancer and lung cancer. PARP1/CDK12-IN-2 can be used for research on triple-negative breast cancer.

(rac)-Talazoparib ((rac)-BMN-673) (Compound 47) is the orally active inhibitor for PARP1/2 with K_i of 1.2 nM and 0.87 nM. (rac)-Talazoparib inhibits cellular PARylation with an EC₅₀ of 2.51 nM. (rac)-Talazoparib causes the accumulation of DNA damage, inhibits proliferation of BRCA1/2-mutated MX-1 cell and Capan-1 cell with IC₅₀ of 0.3 nM and 5 nM. (rac)-Talazoparib exhibits antitumor efficacy in mouse models.

AZ0108 is an inhibitor for poly ADP-ribose polymerase (PARP), which inhibits PARP1, PARP2, PARP3, PARP6, TNKS1, TNKS2, with IC₅₀s of <0.03, <0.03, 2.8, 0.083, 3.2, >3 μM, respectively. AZ0108 prevents centrosome clustering with an EC₅₀ of 0.053 μM, and exhibits cytotoxicity in cell OCI-LY-19 with GI₅₀ of 0.017 μM. AZ0108 exhibits good in vivo pharmacokinetic characters in rat/mouse models.

MC2050 is a selective PARP-1 inhibitor with an IC₅₀ of 119 nM. MC2050 functionally inhibits PARP-1 activity, including hyperactivation induced by oxidative stress, and reduces the poly (ADP-ribosyl) ation level of histone H1. MC2050 protects neuroblastoma cells from oxidative stress-mediated cell death induced by hydrogen peroxide. MC2050 is applicable to research related to neuroblastoma and Burkitt lymphoma.

PARP1-IN-37 (Compound 8) is an orally active and selective poly(ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitor with an IC₅₀ value of 24 nM for PARP1. PARP1-IN-37 inhibits PARP activity in cells with an EC₅₀ value of 3.7 μM. PARP1-IN-37 is promising for research of BRCA-mutated tumors, such as breast and ovarian cancers.

(Neurodegenerative diseases) NDs-IN-1 (Compound 3g) inhibits the activities of key enzymes such as hBACE-1, hAChE and hMAO-B. NDs-IN-1 is a novel non-covalent multi-target inhibitor. NDs-IN-1 is mainly used in the study of neurodegenerative diseases.

PARP1-IN-34 (compound 30) is a selective PARP1 inhibitor with an IC₅₀ of 0.32 nM. PARP1-IN-34 is a subnanomolar PARP1 inhibitor with >1000-fold selectivity against PARP2 with an IC₅₀ of 326 nM. PARP1-IN-34 shows antitumor efficacy_[1].

PARP-2/1-IN-2 (Compound 4a), the enantiomer of Veliparib (HY-10129), is a potent PARP inhibitor with K_is of 2 and 5 nM against PARP-2 and PARP-1, respectively. PARP-2/1-IN-2 has an EC₅₀ of 3 nM in a cell based assay of PARP activity.

OUL245 is a 7-Hydroxy derivative, and a selectively PARP2 inhibitor (IC₅₀=44 nM). OUL245 also inhibits other PARP and TNKS enzymes with IC₅₀s of 2.9-8.8 μM.

PARP-1/2/7-IN-1 (compound 86) is a potent inhibitor of PARP-1/2/7, with the IC₅₀ of ＜ 10 nM.

PP-048 is a selective dual inhibitor of Polθ/PARP1, with IC₅₀ values of 4.9 nM and 6.8 nM for the Polθ helicase/ATPase domain and PARP1, respectively. PP-048 impairs the compensatory DNA repair capacity of homologous recombination-deficient cells by simultaneously inhibiting the DNA repair functions associated with Polθ and PARP1, thereby exacerbating DNA double-strand damage and inducing apoptosis. PP-048 exhibits more potent selective antiproliferative activity against HR-deficient cancer cells. PP-048 can be used in studies related to Polθ/PARP1 dual-target inhibition, synthetic lethality, DNA damage repair, and HR-deficient triple-negative breast cancer.

PARP1-IN-35 (compound T26) is a selective, orally active, cross -the blood-brain barrierPARP1 inhibitor with IC₅₀ values of 0.2, 122 nM for PARP1, PARP2, respectively. PARP1-IN-35 shows antiproliferative activity and anticancer activity. PARP1-IN-35 has the potential for the research of breast cancer.

CEP-9722, the proagent of CEP-8983, is a selective and orally active PARP-1 and PARP-2 inhibitor with IC₅₀s of 20 nM and 6 nM, respectively. CEP-9722 has anticancer effects.

PARP1-IN-53 (Compound 328) is a quinazolinone derivative and PARP1 inhibitor with a PARP1 IC₅₀ of 0.1 nM and selectivity over PARP2, which has a PARP2 IC₅₀ of 23 nM.PARP1-IN-53 can be used for the research of cancer.