TNKS antibody - middle region (ARP33755_P050)
- Known as:
- TNKS (anti-) - middle region (ARP33755_P050)
- Catalog number:
- arp33755_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- TNKS antibody - middle region (ARP33755_P050)
Related genes to: TNKS antibody - middle region (ARP33755_P050)
- Gene:
- TNKS NIH gene
- Name:
- tankyrase
- Previous symbol:
- -
- Synonyms:
- TIN1, TINF1, TNKS1, PARP-5a, PARP5A, pART5
- Chromosome:
- 8p23.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-08
- Date modifiied:
- 2016-03-01
Related products to: TNKS antibody - middle region (ARP33755_P050)
Related articles to: TNKS antibody - middle region (ARP33755_P050)
- Tankyrases (TNKS1 and TNKS2) are multifunctional enzymes of the poly(ADP-ribose) polymerase (PARP) family that regulate cellular homeostasis by catalyzing poly(ADP-ribosyl)ation and stabilizing protein-protein interactions through their ankyrin repeat clusters. By engaging with diverse sets of proteins, TNKSs act as central hubs that coordinate signaling and metabolic pathways. In this review, we discuss how TNKS -protein interactions underpin their roles across multiple biological pathways, including Wnt/β-catenin, YAP and SRC signaling, mTORC1 signaling, DNA damage repair (via PARP crosstalk and recruitment of repair factors), telomere maintenance, cell-cycle regulation, glucose metabolism, cytoskeleton rearrangement, autophagy, proteasomal degradation, and apoptosis. We highlight the structural basis of these interactions, emphasizing ankyrin repeat domain recognition motifs and the consequences of TNKS-mediated PARylation on protein stability and localization. By integrating findings from oncology, virology, and metabolism, we illustrate how TNKS functions as a nodal regulator linking genome stability, signaling fidelity, and metabolic control. The interplay between TNKS and these varied pathways is essential for the well-being of the organism, with its dysregulation having severe biological and clinical consequences, which are discussed here. Finally, we consider therapeutic implications of disrupting TNKS-protein interactions, with particular attention paid to selective small-molecule inhibitors and their translational potential in cancer, viral infections, and degenerative diseases. - Source: PubMed
Publication date: 2026/02/14
Chalabi Hagkarim NafisehGrand Roger J - Colorectal cancer (CRC) is a multifactorial malignancy frequently driven by aberrant activation of the Wnt/β-catenin cascade, which promotes uncontrolled cell proliferation and tumor progression. Tankyrases (TNKS1/TNKS2), members of the PARP family, regulate this pathway by mediating AXIN degradation, thereby stabilizing β-catenin. Inhibition of TNKS can restore AXIN levels and attenuate Wnt signalling, positioning TNKS as a promising therapeutic target. Leveraging the structural diversity, biochemical specificity, and evolutionary refinement of natural microbial compounds, this study screened 36,588 microbial and fungal natural products obtained from the NPATLAS database. High-throughput screening was carried out using Python and the RDKit package, applying stringent physicochemical, structural, and drug-likeliness filters. Exhaustive virtual screening, molecular docking, and 300 ns molecular dynamics (MD) simulations identified two promising candidates, namely Malassezione (NPA018503) and Xenocockiamide B (NPA033189), which exhibited the most favourable and stable binding interactions with TNKS-1, with binding affinities of - 11.45 kcal/mol and - 12.48 kcal/mol, respectively. Further validation through MM-PBSA calculations, Principal component analysis (PCA), DCCM, and free energy landscape (FEL) analyses revealed robust conformational stability and distinct clustering mechanisms of these top hits within the TNKS-1 active site. Density functional theory (DFT) calculations additionally confirmed favourable electronic characteristics for both compounds, including optimal HOMO-LUMO energy gaps and chemical reactivity parameters. Pharmacokinetic profiling indicated high GI absorption, metabolic resilience, and minimal toxicity risk. Although XAV939 is a known TNKS-1 inhibitor, it demonstrated comparatively reduced efficacy across binding and stability metrics. In conclusion, this integrative computational evidence supports microbial-derived compounds as promising natural candidates for TNKS-1 inhibition, offering a new avenue for validation and structure-guided discovery of next-generation microbe-based therapeutics for colorectal cancer. - Source: PubMed
Publication date: 2026/02/19
Sharma DivyaSamreen AdeebaNair AkshadaArumugam Sivakumar - Tankyrases are poly-ADP-ribosyltransferases that orchestrate numerous biological processes involved in disease. Their established regulatory roles, particularly within the WNT/β-catenin pathway, have driven notable drug discovery efforts aimed at inhibiting their catalytic activity. Targeting tankyrases' interaction with proteins through their ARC domains represents an alternative strategy to be explored as a therapeutic approach against specific protein-protein interactions. In this article, we employed a pre-established FRET-based assay to screen the EU-OPENSCREEN libraries for identification of ARC4 inhibitors. We discovered a series of pyrrolone-based compounds, and we synthesized compound S8 (ARCher-142), which binds selectively to ARC4 with a potency of 8 μM. NMR analysis and X-ray crystallography allowed us to identify the binding site and to rationalize the observed selectivity. Despite binding exclusively to ARC4, the inhibitor can attenuate the WNT/β-catenin signaling pathway in cells. Our work demonstrates that targeting single ARC domains is possible, offering an inhibition approach tailored to tankyrase ARC4. - Source: PubMed
Publication date: 2026/01/30
Bosetti ChiaraGalera-Prat AlbertSowa Sven TGade AlexandraBraga CláudiaBrinch Shoshy ANami FaranakPääkkönen JohanPulju VeetiMeling Maureen TCandamo-Lourido MariaWaaler JoClausen Mads HLehtiö Lari - Yes-associated protein (YAP) is a key oncogenic effector and a well-established driver of resistance to anticancer therapies, especially in tumors harboring KRAS mutations. Although YAP is clinically relevant, drug-development efforts that directly inhibit its activity have been limited. Here, we show that basroparib-a selective tankyrase (TNKS) inhibitor that suppresses Wnt signaling-attenuates YAP-driven oncogenic programs by stabilizing angiomotin (AMOT), an endogenous negative regulator of YAP. In colorectal cancer (CRC) cells, basroparib increased AMOT protein abundance, promoted AMOT-YAP complex formation, and enforced cytoplasmic sequestration of YAP, thereby dampening YAP-dependent transcription. Basroparib preferentially sensitized YAP-overexpressing, KRAS-mutant CRC cell lines to MEK inhibition by inhibiting YAP signaling. In MEK inhibitor-resistant CRC models, in which elevated YAP activity mediates escape, basroparib restored drug sensitivity both in vitro and in vivo. The compound also enhanced MEK inhibitor efficacy in other YAP-active tumor types, while exerting minimal effects in YAP-inactive models. Taken together, these results identify basroparib-now progressing through clinical development (Phase I, NCT04505839)-as a promising agent for dual Wnt-YAP pathway blockade and for overcoming therapeutic resistance in YAP-driven cancers. - Source: PubMed
Publication date: 2026/01/22
Kwon Young-JuKim Dong YoungKim YunaKim Uk-IlKim Jae-Sung - We report the design, synthesis, and characterization of a novel series of triazolopyrimidinone and imidazotriazinone derivatives as potent and selective TNKS1/2 inhibitors. These compounds bind to the nicotinamide pocket of TNKS and exhibit strong enzymatic inhibition and cellular Wnt/β-catenin pathway suppression, with minimal off-target activity against other PARP family members. Among them, 11b (STP1002, Basroparib) demonstrated the most favorable profile, with sub-nanomolar IC values for TNKS1/2, high selectivity, and excellent physicochemical and ADME properties. These findings support the further development of STP1002 as a promising therapeutic candidate for Wnt-driven cancers, with potential applications as both a monotherapy and in combination with other targeted agents. - Source: PubMed
Publication date: 2026/01/19
Lim Hwan JungKim Uk-IlKim Kwang RokLee Jun MiPark Kyeong-YongBang Hyung TaeYoon JihyeJo EunsolKim KyungjinHeo Jung-Nyoung