19A449 PARP-5 (Tankyrase)
- Known as:
- 19A449 PARP-5 (Tankyrase)
- Catalog number:
- mc-293
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Kamiya biomedical company
- Gene target:
- 19A449 PARP-5 (Tankyrase)
Related genes to: 19A449 PARP-5 (Tankyrase)
- 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
- Gene:
- TNKS2 NIH gene
- Name:
- tankyrase 2
- Previous symbol:
- -
- Synonyms:
- TNKL, TANK2, PARP-5b, PARP-5c, PARP5B, PARP5C, pART6
- Chromosome:
- 10q23.32
- Locus Type:
- gene with protein product
- Date approved:
- 2001-05-10
- Date modifiied:
- 2016-10-05
Related products to: 19A449 PARP-5 (Tankyrase)
100 mM DEA PARP10X Activated DNA PARP10X PARP Buffer10X PARP Buffer10X PARP Buffer10X PARP Cocktail10X PARP Cocktail10X PARP Cocktail10X PARP Cocktail10X PARP Cocktail PARP182 kDa tankyrase-1-binding protein,Homo sapiens,Human,KIAA1741,TAB182,TNKS1BP1182 kDa tankyrase-1-binding protein,Kiaa1741,Mouse,Mus musculus,Tab182,Tnks1bp1193 kDa vault protein,ADPRTL1,Homo sapiens,Human,KIAA0177,PARP4,PARP-4,PARPL,PARP-related_IalphaI-related H5_proline-rich,PH5P,Poly [ADP-ribose] polymerase 4,Vault poly(ADP-ribose) polymerase,VPARP19A449 PARP-5 (Tankyrase)2 x PARP Cocktail Related articles to: 19A449 PARP-5 (Tankyrase)
- 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 - 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 - Adaptation to hypoxia is essential for cancer survival and is linked to poor prognosis and treatment resistance. This adaptation triggers the expression of genes that promote angiogenesis and metabolic reprogramming, collectively enhancing cancer cell survival, tumor growth, migration and metastasis. Consequently, there is an urgent need for innovative strategies to inhibit tumor adaptation to hypoxic conditions. - Source: PubMed
Publication date: 2025/11/05
Zamudio-Martínez EstebanDelgado-Bellido DanielBorrego-Pérez JerónimoGarcia-Diaz AngelHerrera-Campos Ana BelénRodríguez-Vargas José ManuelOliver F Javier - The ADP-ribosyltransferase tankyrase (with two paralogues, TNKS and TNKS2) plays pivotal roles in diverse cellular processes that encompass signal transduction, including Wnt/β-catenin, Hippo and toll-like receptor (TLR) signalling, mitotic spindle assembly, glucose homeostasis and telomere maintenance, among many other functions. Tankyrase recruits its effectors (substrates and binders) via a degenerate tankyrase-binding motif (TBM) and exerts its activities by subsequent substrate ADP-ribosylation and/or scaffolding. Variants of the TBM, found in diverse proteins, engage the ankyrin repeat cluster (ARC) domains of tankyrase. Yet, whether effector recruitment to tankyrase can be regulated has remained unknown. In this study, we propose that phosphorylation at position eight of the TBM enhances the affinity of effectors for the ARC domains of tankyrase. Using isolated TBM peptides, we demonstrate that phosphorylation of serine, but not tyrosine, strengthens ARC binding by up to an order of magnitude. Interrogation of proteome-wide phosphorylation data reveals that phosphorylation at position eight in the TBM is enriched in proteins that support centrosome function/localization. Our findings suggest that TBM phosphorylation may serve as an effector-specific mechanism for tankyrase recruitment/retention, providing an additional layer of regulation to control tankyrase. - Source: PubMed
Publication date: 2025/10/15
Broadway Benjamin JPollock KatieCronin NoraRottapel RobertSicheri FrankGuettler Sebastian