TNKS2/PARP5B
Tankyrase 2 (TNKS2, also known as PARP5B) is a poly(ADP-ribose) polymerase (PARP) that catalyzes poly(ADP-ribosyl)ation of substrate proteins, regulating β-catenin signaling and DNA repair pathways[1][2]. Mechanistically, TNKS2 promotes Axin degradation through poly(ADP-ribosyl)ation, thereby activating Wnt/β-catenin signaling, which is essential for neuronal development, tumor proliferation, and viral replication[1][3]. TNKS2 contributes to both homologous recombination and nonhomologous end-joining DNA repair, cooperating with MDC1 and other repair factors to maintain genomic stability[2][4]. Compared with its isoform TNKS1, TNKS2 can be selectively targeted due to distinct structural features within its PARP catalytic domain, enabling isoform-specific inhibition[5][6]. In disease models, TNKS2 depletion or inhibition reduces tumor growth, enhances apoptosis, and modulates antiviral responses, demonstrating relevance in cancer and influenza A virus infection[4][3][6]. Small-molecule inhibitors such as XAV939, E7449, and newly developed TNKS2-selective compounds engage the catalytic site, stabilize Axin, suppress Wnt signaling, and exhibit antitumor or antiviral effects in vitro and in vivo[5][6][7]. Structure-guided drug design based on high-resolution TNKS2 crystal structures has enabled the development of potent, selective inhibitors with favorable pharmacokinetics and minimal off-target activity[5][6][8]. These inhibitors serve as valuable tools for dissecting TNKS2-specific pathways, understanding DNA repair dynamics, and evaluating therapeutic strategies in Wnt-dependent cancers[9][10][7].
References:
- [1]. Qiu W, et al. Insights into the binding of PARP inhibitors to the catalytic domain of human tankyrase-2. Acta Crystallogr D Biol Crystallogr. 2014 Oct;70(Pt 10):2740-53. [Content Brief]
- [2]. Tomassi S, et al. From PARP1 to TNKS2 Inhibition: A Structure-Based Approach. ACS Med Chem Lett. 2020 Feb 3;11(5):862-868. [Content Brief]
- [3]. Bamunuarachchi G, et al. Tankyrases positively regulate influenza A virus replication via type I interferon response. J Virol. 2025 Oct 23;99(10):e0129825. [Content Brief]
- [4]. Xu Y, et al. Rational design, synthesis and biological evaluation of dual PARP-1/2 and TNKS1/2 inhibitors for cancer therapy. Eur J Med Chem. 2022 Jul 5;237:114417. [Content Brief]
- [5]. Zimmerman J, et al. A potent and selective TNKS2 inhibitor for tumor-selective WNT suppression. bioRxiv [Preprint]. 2025 Mar 7:2025.03.04.641305. [Content Brief]
- [6]. Mashimo M, et al. Tankyrase Regulates Neurite Outgrowth through Poly(ADP-ribosyl)ation-Dependent Activation of β-Catenin Signaling. Int J Mol Sci. 2022 Mar 4;23(5):2834. [Content Brief]
- [7]. Wu J, et al. PARP5B is required for nonhomologous end joining during tumorigenesis in vivo[J]. Molecular Carcinogenesis, 2022, 61(1): 85-98.
- [8]. Nagy Z, et al. Tankyrases Promote Homologous Recombination and Check Point Activation in Response to DSBs. PLoS Genet. 2016 Feb 4;12(2):e1005791. [Content Brief]
- [9]. Wahlberg E, et al. Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors. Nat Biotechnol. 2012 Feb 19;30(3):283-8. [Content Brief]
- [10]. McGonigle S, et al. E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015 Dec 1;6(38):41307-23. [Content Brief]
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TNKS2/PARP5B Related Products (38)
Related Products (38)
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PARP1/2/TNKS1/2-IN-1
0 ImagesPARP1/2/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.
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OM-1700
0 ImagesCat. No.: HY-145266CAS No.: 2406276-78-4OM-1700 is a potent tankyrase inhibitor with IC50s of 127 and 14 nM for tankyrase 1 and tankyrase 2, respectively. OM-1700 reduces cell growth in the colon cancer cell line COLO 320DM (GI50=650 nM).
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PARP1-IN-44
0 ImagesCat. No.: HY-178032PARP1-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.
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ATR/PARP1-IN-1
0 ImagesCat. No.: HY-174828ATR/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.
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TC-E 5001
0 ImagesCat. No.: HY-108516CAS No.: 865565-29-3
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PARP14 inhibitor 1
0 ImagesCat. No.: HY-172806CAS No.: 3035493-13-8PARP14 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.
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TNKS-IN-1
0 ImagesTNKS-IN-1 is a selective and potent tankyrase (TNKS1/TNKS2) inhibitor with IC50 values of 7.9 nM and 8.7 nM. TNKS-IN-1 induces axin2 accumulation with an EC50 of 1500 nM. TNKS-IN-1 can antagonize the Wnt signal transduction pathway by stabilizing axin proteins and promoting β-catenin degradation. TNKS-IN-1 can be used for the research of colorectal cancer.
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TNKS-IN-4
0 ImagesCat. No.: HY-12602CAS No.: 1507362-06-2TNKS-IN-4 (compound 49) is an orally active tankyrase (TNKS) inhibitor with IC50 values of 0.1 nM and 7.6nM for TNKS1 and TNKS2, respectively. TNKS-IN-4 can be used for study of APC-mutant colorectal cancer.
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OUL245
0 ImagesCat. No.: HY-W294889CAS No.: 1023814-45-0
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TNKS-2-IN-4
0 ImagesCat. No.: HY-167762CAS No.: 1613436-03-5TNKS-2-IN-4 (Compound 17) is a selective TNKS-2 inhibitor with an IC50 of 19 nM. TNKS-2-IN-4 exhibits anticancer activity against colorectal cancer.
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TNKS-2-IN-3
0 ImagesCat. No.: HY-172747CAS No.: 2580941-64-4TNKS-2-IN-3 (Compound 5) is a selective competitive tankyrase 2 (TNKS2) inhibitor with an IC50 value of 0.3 nM, showing over 20-fold selectivity over TNKS1 and more than 100-fold selectivity over PARP1/2. TNKS-2-IN-3 stabilizes axin and suppresses the Wnt/β-catenin pathway by inhibiting TNKS2-mediated ADP-ribosylation, exhibiting antiproliferative activity in colorectal cancer cells. TNKS-2-IN-3 is proming for rasearch of solid tumors with aberrant Wnt pathway activation, such as colorectal cancer.
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EXQ-2d
0 ImagesCat. No.: HY-168925EXQ-2d is the inhibitor for tankyrase and inhibits TNKS1 and TNKS2 with an IC50 of 48.8 nM and 13.8 nM (pIC50=7.31 and 7.86). EXQ-2d inhibits WNT/β-catenin signaling pathway with IC50 of 515 nM. EXQ-2d exhibits anti-proliferative activity in cancer cells COLO 320DM and RKO with GI50 of 4.9 μM and 77 μM.
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