Request Demo

Last update 08 May 2025

NUDT14

Last update 08 May 2025

Basic Info

Synonyms

Nucleoside diphosphate-linked moiety X motif 14, nudix hydrolase 14, Nudix motif 14

+ [5]

Introduction

Hydrolyzes UDP-glucose to glucose 1-phosphate and UMP and ADP-ribose to ribose 5-phosphate and AMP. The physiological substrate is probably UDP-glucose. Poor activity on other substrates such as ADP-glucose, CDP-glucose, GDP-glucose and GDP-mannose.

Drugs associated with NUDT14

NUDT5/14 Antagonist(University of Oxford)

Target

NUDT14 x NUDT5

Mechanism

NUDT14 antagonists [+1]

Active Org.

University of Oxford

Originator Org.

University of Oxford

Active Indication

Breast Cancer

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with NUDT14

100 Translational Medicine associated with NUDT14

0 Patents (Medical) associated with NUDT14

Literatures (Medical) associated with NUDT14

01 Feb 2025·Nature Genetics

Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain

Article

Author: Thompson, Leslie M ; Li, Jason Sheng ; Li, Wei ; La Spada, Albert R ; Michels, Sebastian ; Philippe, Julien ; Colwin, Michael R ; Wu, Jie ; Sallam, Tamer ; Chen, Chaorong ; Cui, Ya ; Wang, Dan ; Arnold, Frederick J

Tandem repeat (TR) size variation is implicated in ~50 neurological disorders, yet its impact on gene regulation in the human brain remains largely unknown. In the present study, we quantified the impact of TR size variation on brain gene regulation across distinct molecular phenotypes, based on 4,412 multi-omics samples from 1,597 donors, including 1,586 newly sequenced ones. We identified ~2.2 million TR molecular quantitative trait loci (TR-xQTLs), linking ~139,000 unique TRs to nearby molecular phenotypes, including many known disease-risk TRs, such as the G₂C₄ expansion in C9orf72 associated with amyotrophic lateral sclerosis. Fine-mapping revealed ~18,700 TRs as potential causal variants. Our in vitro experiments further confirmed the causal and independent regulatory effects of three TRs. Additional colocalization analysis indicated the potential causal role of TR variation in brain-related phenotypes, highlighted by a 3'-UTR TR in NUDT14 linked to cortical surface area and a TG repeat in PLEKHA1, associated with Alzheimer's disease.

01 Jan 2025·Current Medicinal Chemistry

Significance of Aneuploidy in Predicting Prognosis and Treatment Response of Uveal Melanoma

Article

Author: Zhou, Chenchen ; Jiang, Qin ; Liu, Jinghua ; Jin, Ling ; Zhang, Xiaoqian

Aims:This study aimed to improve personalized treatment strategies and predict survival outcomes for patients with uveal melanoma (UM).Background:Copy number aberrations (CNAs) have been considered as a main feature of metastatic UM.Objective:This study was designed to explore the feasibility of using copy number variation (CNV) in UM classification, prognosis stratification and treatment response.Methods:The CNV data in the TCGA-UVM cohort were used to classify the samples. The differentially expressed genes (DEGs) between subtypes were screened by the “Limma” package. The module and hub genes related to aneuploidy score were identified by performing weighted gene co-expression network analysis (WGCNA) on the DEGs. Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to train the hub genes for developing a prognosis model for UM. Finally, the expression levels of the screened prognostic key genes were verified in UM cells, and the cell migration and invasion abilities were detected using real-time quantitative PCR (qRT-PCR) and transwell assay.Results:The UM samples were divided into 3 CNV subtypes, which differed significantly in overall survival (OS) and disease-specific survival (DSS). C1 had the shortest OS and DSS and the highest level of immune infiltration. A total of 2036 DEGs were obtained from the three subtypes. Eighty hub genes with the closest correlation with aneuploidy scores were selected by WGCNA. Univariate Cox and LASSO regression-based analyses finally determined eight genes as the key prognostic genes, including HES6, RNASEH2C, NQO1, NUDT14, TTYH3, GJC1, FKBP10, and MRPL24. A prognostic model was developed using the eight genes, demonstrating a strong prediction power. Differences in the response to immunotherapy among patients in different risk groups were significant. We found that high-risk patients were more sensitive to two drugs (Palbociclib_ 1054 and Ribociclib_1632), while low-risk patients were more sensitive to AZD1208_1449, ERK_2440_1713, Mirin_1048, and Selumetinib_1736.Conclusion:UM in this study was divided into three CNV subtypes, and a model based on eight aneuploidy score-related genes was established to evaluate the prognosis and drug treatment efficacy of UM patients. The current results may have the potential to help the clinical decision-making process for UM management.

09 May 2024·Journal of Medicinal Chemistry

Unexpected Noncovalent Off-Target Activity of Clinical BTK Inhibitors Leads to Discovery of a Dual NUDT5/14 Antagonist

Article

Author: Raux, Brigitt ; Elkins, Jonathan M. ; Huber, Kilian V. M. ; Seupel, Raina ; Sloman, David L. ; Rogers, Catherine ; Fedorov, Oleg ; Simelis, Klemensas ; Ward, Jennifer ; Marques, Anne-Sophie M. C. ; Bennett, James ; Balıkçı, Esra ; Bauer, Ludwig G. ; Schützenhofer, Kira ; Ahel, Ivan ; Szommer, Tamas ; Cheng, Carol ; Singh, Usha ; Buchan, Karly ; Brennan, Paul E.

Cofactor mimicry represents an attractive strategy for the development of enzyme inhibitors but can lead to off-target effects due to the evolutionary conservation of binding sites across the proteome. Here, we uncover the ADP-ribose (ADPr) hydrolase NUDT5 as an unexpected, noncovalent, off-target of clinical BTK inhibitors. Using a combination of biochemical, biophysical, and intact cell NanoBRET assays as well as X-ray crystallography, we confirm catalytic inhibition and cellular target engagement of NUDT5 and reveal an unusual binding mode that is independent of the reactive acrylamide warhead. Further investigation of the prototypical BTK inhibitor ibrutinib also revealed potent inhibition of the largely unstudied NUDIX hydrolase family member NUDT14. By exploring structure-activity relationships (SARs) around the core scaffold, we identify a potent, noncovalent, and cell-active dual NUDT5/14 inhibitor. Cocrystallization experiments yielded new insights into the NUDT14 hydrolase active site architecture and inhibitor binding, thus providing a basis for future chemical probe design.

Analysis

Perform a panoramic analysis of this field.

view full example data

Hiro LS Researcher

The AI Search Engine Built to Accelerate Biopharma Decisions

Search across billion-scale life sciences data to uncover signals, validate evidence, and act with confidence.

Ask any biopharma research question→

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, Patsnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Discover Synapse Data Servers

Synapse data is now integrated into the PatSnap LS Model Context Protocol (MCP) service. Customize your LLM agent now using our MCP server!

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

NUDT14

Basic Info

Related

Analysis