Ask about this productRelated genes to: TNIK antibody
- Gene:
- TNIK NIH gene
- Name:
- TRAF2 and NCK interacting kinase
- Previous symbol:
- -
- Synonyms:
- KIAA0551
- Chromosome:
- 3q26.2-q26.31
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-26
- Date modifiied:
- 2018-11-19
Related products to: TNIK antibody
Related articles to: TNIK antibody
- Macrocyclization strategies that generate conformationally constrained peptide scaffolds within nucleotide-encoded library screening platforms have significantly advanced the discovery of de novo bioactive peptides. We previously reported ribosomal synthesis of topologically defined thioisoindole-bridged bicyclic (TiB) peptides, but complete conversion required overnight incubation. Here, we reengineer the key ribosomally incorporated substrate to accelerate TiB formation to full conversion within 2 h. This was followed by a streptavidin-based pulldown step to efficiently remove linear species and purify the desired TiB peptides. The optimized chemistry was incorporated into the RaPID (Random nonstandard peptides integrated discovery) system to enable de novo identification of TiB peptide ligands. As a proof of concept, two complementary TiB libraries were screened against Traf2- and NCK-interacting kinase (TNIK). Of the five TiB candidates identified, four exhibited nanomolar affinity for TNIK (best K = 12.3 nM), and the most potent ligand, TK7, inhibited TNIK kinase activity with an IC of 60 nM. X-ray crystallography revealed that TK7 adopts a unique binding mode on the TNIK surface. Collectively, these findings establish a practical platform for TiB peptide discovery, highlighting their potential in early-stage peptide drug development. - Source: PubMed
Publication date: 2026/08/13
Zhang YueVinogradov Alexander AHamada KeisukeSun YinSengoku ToruSuga Hiroaki - In the developing human placenta, three subtypes of trophoblast cells, cytotrophoblasts (CTBs), extravillous trophoblasts (EVTs), and syncytiotrophoblasts (STBs), mediate critical functions essential for a successful pregnancy. CTBs constitute the stem/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal-fetal exchange interface and secrets human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label-free liquid chromatography tandem Mass Spectrometry (LC/MS/MS) to profile proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1 and TNIK are essential for maintaining the hTSC stem state. Additionally, atypical protein kinase C isoforms PKC zeta is essential for STB development, while PTK2B, SRC, TRIO and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy. - Source: PubMed
Publication date: 2026/07/24
Kumar RajnishDasgupta PurbasaRay SomaPaul Soumen - Dysregulation of metabolic signalling pathways, such as Wnt/β-catenin, is a hallmark of various cancers including colorectal cancer, lung squamous cell carcinoma, papillary thyroid carcinoma, multiple myeloma etc. TRAF2 and NCK-interacting kinase (TNIK), a serine/threonine kinase, plays a critical role in this pathway by phosphorylating TCF4, thereby promoting transcription of oncogenic genes linked to cell proliferation, stemness, and therapeutic resistance. Owing to its central role across multiple tumor types, TNIK is a promising target for small-molecule drug development. This study utilized an integrated computer-aided drug design (CADD) strategy to identify novel TNIK inhibitors. Ligand-based virtual screening (LBVS) was initiated using a pharmacophore model based on known inhibitors to screen over 1 billion PubChem compounds. Filtering via cheminformatics protocols (PAINS, Lipinski's rules, and molecular descriptors) in KNIME narrowed the library to 25,082 candidates. These were subjected to structure-based virtual screening (SBVS) using molecular docking against TNIK (PDB ID: 6RA7). The top 100 hits were assessed for ADMET properties using DruMAP v2.0, identifying three lead compounds: PubChem-11590224, -9168610, and -121049323. These were further validated through 200-ns molecular dynamics (MD) simulations in triplicate using GROMACS, confirming stable binding interactions. MM/PBSA free energy calculations revealed favorable binding energies, comparable to clinical-phase TNIK inhibitor INS018_055. This LBVS-SBVS-ADMET-MD pipeline effectively identified three promising TNIK inhibitors, providing a solid foundation for future experimental validation and potential development of targeted therapies for Wnt-driven malignancies. - Source: PubMed
Publication date: 2026/07/21
Mishra Diwakar KumarKumar RajnishBaidya Anurag TkJangra JatinMisra Shashi KiranKumar SanjayKumar Ajay - The organ- and stage-specific diversity of megakaryocytes (MKs) has prompted a reassessment of their distribution and functions. By integrating single-cell transcriptomic data across multiple organs and developmental stages, we identified previously unreported MK and platelet markers, including Tnik, a key regulator of MK function and platelet production. Using these markers alongside established ones, we developed a machine learning-based MK identification system (MKIDS) that enables MK detection in the brain, heart, and placenta in mice and humans. Functional studies demonstrated that brain-resident MKs are essential for neural development, underscoring organ-specific roles of MKs in regulating tissue development and function. Transcriptomic integration of MKs across organs and stages, with functional validation, revealed a developmental shift in platelet production-from a mitochondria-low to a mitochondria-enriched subpopulation. Our findings offer a transformative perspective on the MK system, highlighting its cellular diversity, functional complexity, and developmental dynamics. - Source: PubMed
Publication date: 2026/05/11
Xia MeijuanMa YeziCai YifeiZhao JingjingZhong YaoGuo SibeiLi MinminSu PeiShen BiaoHe HuizhenChen XiaoyuanZheng LinLi LeHuo ZiqiZhou WenWang FeiLiu CuicuiWang HongtaoZhou Jiaxi - Medulloblastoma (MB) is the most common malignant pediatric brain tumor and comprises molecularly and clinically distinct subgroups with highly variable outcomes. While survival rates exceed 80% in some subgroups, others remain associated with substantially poorer prognosis and increased risk of relapse. Current treatment includes surgery, radiation, and chemotherapy, which can result in significant long-term treatment-related morbidity. These challenges highlight the need to identify novel biomarkers and potential therapeutic targets to improve risk stratification and enable more tailored treatment approaches. The Traf2- and Nck-interacting kinase (TNIK) is a regulator of Wnt/β-catenin signaling and has been implicated in the progression of several cancers, but its role in MB remains unclear. - Source: PubMed
Publication date: 2026/05/08
Klaus Franz-LeonardMaragkou TheoniDelbridge ClaireEberhardt Charles GHewer EkkehardGocke AntoniaRadpour RaminMawrin ChristianMogler CarolinNeumann Julia EForster Stefan