tnks1

PARP1/2/TNKS1/2-IN-1 is a multi-target inhibitor of PARP-1, PARP-2, TNKS1, and TNKS2, with potential anti-tumor activity that induces apoptosis.

MN-64 is a tankyrases inhibitor, showed 6 nM potency against tankyrase 1, isoenzyme selectivity, and Wnt signaling inhibition.

TNKS-2-IN-1 is a TNKS-2 inhibitor.TNKS-2-IN-1 inhibits TNKS-1 and TNKS-2 with IC50s of 259 nM and 1100 nM, respectively.TNKS-2-IN-1 has antimicrobial activity against E. coli and S. aureus.TNKS-2-IN-1 inhibits the release of IL-1β from the NLRP3 inflammasome (IC50: 5 μM) by inhibiting IL-1β release from ATP-stimulated J1A.774 cells.

Tankyrase-IN-2 is a selective, potent and orally active inhibitor of tankyrase with IC50s of 10, 7, and 710 nM for TNKS1, TNKS2 as well as PARP1, respectively

K-756 is a direct and selective inhibitor of tankyrase (TNKS), inhibiting the ADP-ribosylation activity of TNKS1 [IC50 = 31 nM] and TNKS2 [IC50 = 36 nM].

JW 55 (JW55) is an effective and selective β-catenin signaling pathway inhibitor, works by inhibition of the PARP domain of tankyrase 1 and tankyrase 2 (TNKS1/2).

XAV-939 (NVP-XAV939) is a Tankyrase (TNKS) inhibitor that inhibits TNKS1 and TNKS2 (IC50=11/4 nM). XAV-939 selectively inhibits Wnt/β-catenin-mediated transcription.

Nesuparib (JPI-547/OCN-201) is a potent PARP inhibitor with inhibitory effects on PARP and TNKS1.Nesuparib has antitumor activity and can be used in the treatment of tumors, endocrine and metabolic disorders, genitourinary disorders, and can be used in the study of neuropathic pain, neurodegenerative disorders, and cardiovascular diseases.

AZ6102 is a potent TNKS1/2 inhibitor that has 100-fold selectivity against other PARP family enzymes and shows IC50 of 5 nM for Wnt pathway inhibition in DLD-1 cells.

G007-LK is a selective inhibitor of TNKS1 and TNKS2, with IC50s of 46 nM and 25 nM, respectively.

TNKS1/2-IN-1 is a potent tankyrase (TNKS1/2) inhibitor with pIC50 values ranging from 7.1 to 8.2, used in research targeting cancer, fibrosis, and other hyperproliferative diseases.

PARP10-IN-3 is a potent and selective mono-Adp-ribotransferase PARP10 inhibitor that inhibits human PARP10 (IC50:480 nM). PARP10-IN-3 also inhibited human PARP2 and human PARP15 with IC50 values of 1.7 μM.

PARP10-IN-2 is a potent inhibitor of PARP10, a mono-ADP-ribosyltransferase, with an IC50 value of 3.64 μM for human PARP10. It also inhibits PARP2 and PARP15, with IC50 values of 27 μM and 11 μM, respectively.

EXQ-2d is an inhibitor of tankyrase, effectively targeting TNKS1 and TNKS2 with IC50 values of 48.8 nM and 13.8 nM (pIC50=7.31 and 7.86), respectively. Additionally, EXQ-2d suppresses the WNT/β-catenin signaling pathway with an IC50 of 515 nM. It demonstrates antiproliferative activity in cancer cells COLO 320DM and RKO, with GI50 values of 4.9 μM and 77 μM, respectively.

TDI-012804 is a TNKS2 inhibitor that selectively inhibits endogenous TNKS2 protein within cells. It enhances the expression of AXIN1 protein in Tnks1 heterozygous (Tnks1HET) and knockout (Tnks1KO) cells. TDI-012804 suppresses the proliferation of ApcQ1405X/Tnks1KO organoids with an EC50 of 59.1 nM and exhibits selective toxicity towards Tnks1KO AKP-G12D and AKP-G13D organoids.

TNKS-2-IN-3 (Compound 5) is a selective and competitive inhibitor of Tankyrase 2 (TNKS2), with an IC50 value of 0.3 nM. It exhibits over 20-fold selectivity for TNKS2 compared to TNKS1 and more than 100-fold selectivity over PARP1/2. By inhibiting TNKS2-mediated ADP ribosylation, TNKS-2-IN-3 stabilizes axin and suppresses the Wnt/β-catenin pathway, demonstrating antiproliferative activity in colorectal cancer cells. TNKS-2-IN-3 holds potential for research in solid tumors with aberrant Wnt pathway activation, such as colorectal cancer.

dual tankyrase (TNKS) inhibitor

CAY10753 is an inhibitor of tankyrase 2 (TNKS2; IC50= 0.3 nM).1It is selective for TNKS2 over TNKS1 (IC50= 6.1 nM), as well as poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 (IC50s = 89.6 and 37.8 nM, respectively). CAY10753 inhibits proliferation of DLD-1 colorectal cancer cells when used at a concentration of 1 μM. 1.Tomassi, S., Pfahler, J., Mautone, N., et al.From PARP1 to TNKS2 inhibition: A structure-based approachMed. Chem. Lett.(2020)

E7449 (UNII-9X5A2QIA7C) 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.

PARP1-IN-11 (compound 49) is a potent PARP1 inhibitor with an IC50 value of 0.082 μM, demonstrating complete inhibition of PARP1 and substantial inhibition of PARP3, TNKS1, and TNKS2 [1].

OM-1700 is a potent inhibitor of tankyrase, acting on tankyrase 1 (IC50: 127 nM) and tankyrase 2 (IC50: 14 nM). OM-1700 inhibits the growth of colon cancer cell lines and inhibits COLO 320DM cells (GI50: 650 nM).

OM-153 is a potent inhibitor of tankyrase, acting on tankyrase 1 (IC50: 13 nM) and tankyrase 2 (IC50: 2 nM), and inhibiting WNT/β-linked protein signaling and proliferation in COLO 320DM.

ME0328 is a potent, selective PARP inhibitor with an IC50 of 0.89 μM for PARP3, showing approximately 7-fold selectivity over PARP1.

AZ0108 is an orally bioavailable, potent PARP1,2,6 inhibitor that potently inhibits centrosome clustering and is suitable for in vivo efficacy and tolerability studies. AZ0108 has been utilized as in vitro tools and in vivo probes to investigate the biological consequences of inhibiting centrosome clustering through PARP enzymes. AZ0108 is more selective in its enzyme inhibition profile and effects on cellular pathways and phenotypes. Specifically, AZ0108 inhibits PARPs 1, 2, and 6 with approximately 100-fold selectivity against PARP3 and TNKS1. Consistent with this lack of potencytowards tankyrase, AZ0108 is not active in a DLD-1 Wnt luciferase reporter assay.