PARP14 Inhibitor

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.

RBN-3143 is a potent and NAD+-competitive catalytic PARP14 inhibitor with an IC₅₀ value of 4 nM. RBN-3143 inhibits PARP14-mediated ADP-ribosylation and stabilizes PARP14 in cell lines. RBN-3143 can be used in research of lung inflammation.

PARP14 inhibitor H10, compound H 10, is a selective inhibitor against PARP14 (IC₅₀=490 nM), over other PARPs (≈24 fold over PARP1). PARP14 inhibitor H10 induces caspase-3/7-mediated cell apoptosis.

GeA-69 is a selective, allosteric inhibitor of poly-adenosine-diphosphate-ribose polymerase 14 (PARP14) targeting macrodomain 2 (MD2), with a K_d value of 2.1 μM. GeA-69 involves in DNA damage repair mechanisms and prevents recruitment of PARP14 MD2 to sites of laser-induced DNA damage.

PARP10-IN-3 is a selective mono‐ADP‐ribosyltransferase PARP10 inhibitor with an IC₅₀ of 480 nM for human PARP10. PARP10-IN-3 reveals potent inhibition on PARP2 and PARP15 with IC₅₀s of 1.7 μM for human PARP2 and human PARP15, respectively.

PARP10-IN-2 is a potent mono‐ADP‐ribosyltransferase PARP10 inhibitor with an IC₅₀ of 3.64 μM for human PARP10. PARP10-IN-2 reveals potent inhibition on PARP2 and PARP15 with IC₅₀s of 27 μM and 11 μM for human PARP2 and human PARP15, respectively.

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.

TIQ-A is a potent TNKS (poly-ART, PARP) inhibitor, with an IC₅₀ of 24 nM for TNKS2. TIQ-A is a potential anti-ischemic agent.

ART-IN-1 (compound 7) is a selective PARP inhibitor with IC₅₀s of 19, 22, 2.4, >100, 1.1 µM for PARP2, TNKS2, PARP10, PARP14, PARP15, respectively.

ARTD10/PARP10-IN-1 (compound 23) is a potent and non-selective PARP inhibitor, targeting to mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14, ARTD10/PARP10 and poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) with IC₅₀s of 1.7 μM, 1.6 μM, 0.8 μM, and 4.4 μM, respectively.

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.

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.

PARP14 inhibitor 2 (Compound 3) is an orally active and highly selective PARP14 inhibitor with an IC₅₀ value of <30 nM. PARP14 inhibitor 2 inhibits the mono-ADP-ribosyltransferase activity of PARP14 and regulates IFN-γ and IL-4 signaling, reversing protumor macrophage polarization and inhibiting anti-tumor inflammatory responses. PARP14 inhibitor 2 is promising for research of PARP14-related diseases such as tumors, atopic dermatitis and autoimmune diseases.

ARTD10/PARP10-IN-2 (compound 19) is a potent and non-selective PARP inhibitor, targeting to mono-ADP-ribosyltransferases ARTD10/PARP10 and poly(ADP-ribose) polymerase-1 ARTD1/PARP1 with IC₅₀s of 2.0 μM, and 9.7 μM, respectively.