PARP7 Inhibitor

RBN-2397 is a potent, accross species and orally active NAD⁺ competitive inhibitor of PARP7 (IC₅₀<3 nM). RBN-2397 selectively binds to PARP7 (K_d=0.001 μM) and restores IFN signaling. RBN-2397 has the potential for the study of advanced or metastatic solid tumors.

RBN012759 is a potent, selective and orally active inhibitor of PARP14, with an IC₅₀ of <3 nM. RBN012759 displays 300-fold selectivity over the monoPARPs and 1000-fold selectivity over the polyPARPs. RBN012759 decreases pro-tumor macrophage function and elicits inflammatory responses in tumor explants.

OUL232 is a potent inhibitor of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15. OUL232 is the most potent PARP10 inhibitor described to date (IC₅₀=7.8 nM), as well as the first PARP12 inhibitor ever reported.

PARP7-IN-15 is an orally active and selective PARP7 inhibitor with an IC₅₀ of 0.56 nM. PARP7-IN-15 inhibits the enzymatic activity of PARP7 and induces anti-tumor activity against lung cancer in vivo. PARP7-IN-15 can be used for the research of lung cancer.

KMR-206 is a PARP7 inhibitor with an IC₅₀ of 13.7 nM. KMR-206 relieves AHR-mediated transcriptional repression and enhances CYP1A1 expression in the presence of TCDD. KMR-206 induces the STING-dependent IFN-β signaling pathway and increases the levels of STAT1, pSTAT1 and nuclear PARP7 in cancer cells. KMR-206 reduces the viability of lung adenocarcinoma cells, enhances radiation-induced immunogenic signals, and induces the production of immunogenic signals in glioblastoma cancer stem cells. KMR-206 destabilizes FRA1 to increase IRF1 levels and promotes the IRF3-CBP/p300 interaction. KMR-206 can be used in studies related to lung adenocarcinoma and glioblastoma.

TIPARP-IN-1 (Compound 15) is a selective PARP7 (TIPARP) (2,3,7,8-Tetrachlorodiben-zo-p-dioxin(TCDD)-inducible PARP) inhibitor with an IC₅₀ of 2.15 nM. TIPARP-IN-1 can restore IFN signaling pathway in tumors by inhibiting TIPARP. TIPARP-IN-1 selectively activates the anti-tumor immune response in the tumor microenvironment and avoids the production of systemic cytokines. TIPARP-IN-1 can be used for research of head and neck squamous cell carcinoma.

PARP7-IN-25 is a PARP7 inhibitor with an IC₅₀ of 1.582 nM.PARP7-IN-25 inhibits enzymatic activity of PARP7. PARP7-IN-25 inhibits proliferation of lung cancer cells.PARP7-IN-25 can be used for the research of PARP7-related cancer.

PARP7-IN-16 (compound 36) is a potent, selective and orally active inhibitor of PARP-1/2/7, with IC₅₀s of 0.94, 0.87 and 0.21 nM, respectively. PARP7-IN-16 can be used for the research of breast cancer and prostate cancer.

PARP7-IN-16 free base is the free base form of PARP7-IN-16 (HY-156419). PARP7-IN-16 free base is a selective and orally active inhibitor of PARP-1/2/7, with IC₅₀s of 0.94, 0.87 and 0.21 nM, respectively. PARP7-IN-16 can be used for the research of breast cancer and prostate cancer.

PARP7-IN-17 is a potent inhibitor of PARP7 with IC₅₀ of 4.5 nM that has oral bioavailability. PARP7-IN-17 displays antitumor effect.

PARP7-IN-22 (XLY-1) is a PARP7 inhibitor with an IC₅₀ of 0.6 nM. PARP7-IN-22 (XLY-1) is orally active, enhances type I interferon signaling in vitro, restores type I interferon signaling, promotes T cell infiltration into tumor tissues, and significantly inhibits tumor growth. PARP7-IN-22 shows promise for research in the field of cancer immunotherapy.

YCH1899 is an orally active PARP inhibitor, with an IC₅₀< 0.001 nM for PARP1/2. YCH1899 exhibits distinct antiproliferation activity against Olaparib (HY-10162)-resistant and Talazoparib (HY-16106)-resistant Capan-1 cells (Capan-1/OP and Capan-1/TP cells) , with IC₅₀ values of 0.89 and 1.13 nM, respectively. YCH1899 has acceptable pharmacokinetic properties in rats.

PARP1/2/TNKS1/2-IN-1 is a potent and selective dual PARP-1/2 and TNKS1/2 inhibitor with IC₅₀ values of 0.25 nM, 1.2 nM, 13.5 nM and 4.15 nM for PARP-1, PARP-2, TNKS1 and TNKS2, respectively. PARP1/2/TNKS1/2-IN-1 suppresses Wnt/β-catenin signaling, decreases pADPr and BRCA1 expression, induces DNA damage, promotes apoptosis, and arrests the cell cycle at the G2/M phase. PARP1/2/TNKS1/2-IN-1 can be used for the study of on colorectal cancer and triple-negative breast cancer.

Antitumor agent-170 (Compound C6) exhibits inhibitory activities against PD-1/PD-L1 interaction and PARP7, with IC₅₀ of 0.342 μM and 7.05 nM. Antitumor agent-170 exhibits a high affinity to human PD-L1, with a K_i of 9.31 nM. Antitumor agent-170 restores the T cell function and increases IFN-γ secretion. Antitumor agent-170 exhibits antitumor efficacy against melanoma in mouse models and good pharmacokinetic characteristics.

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.

PARP14 inhibitor 1 is an orally active, selective PARP14 inhibitor with an IC₅₀ of 5.52 nM. PARP14 inhibitor 1 exhibits favorable pharmacokinetic properties and in vivo safety. PARP14 inhibitor 1 enhances and stabilizes intracellular endogenous PARP14 protein levels, while effectively reducing the expression levels of IL-4, IL-13 and IL-17A. PARP14 inhibitor 1 can be used in research related to atopic dermatitis.

PARP7-IN-12 is a potent PARP7 Inhibitor with an IC₅₀ value of 7.836 nM. PARP7-IN-12 can be used in research of cancer.

PARP7-IN-23 (compound 56) is a potent PARP7 inhibitor with an EC₅₀ of 0.915 nM for pSTAT1 in NCI-H1373 cells. PARP7-IN-23 has the potential for cancer research.

Antitumor agent-169 (Compound B3) is a dual inhibitor PD-1/PD-L1 interaction and PARP7, with IC₅₀s of 0.426 μM and 2.50 nM. Antitumor agent-169 exhibits an affinity to human PD-L1, with K_i of 20.2 nM. Antitumor agent-169 restores the T cell function, increases IFN-γ secretion. Antitumor agent-169 inhibits cell viability of MDA-MB-231 and Jurkat T, exhibits antitumor efficacy against melanoma in mouse model and good pharmacokinetic characteristics.