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Last update 08 May 2025

CHKA

Last update 08 May 2025

Basic Info

Synonyms

CHETK-alpha, CHKA, ChoKα

+ [5]

Introduction

Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis (PubMed:17007874, PubMed:19915674, PubMed:23416529, PubMed:34077757). Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis (PubMed:17007874, PubMed:19915674). Has higher activity with choline (PubMed:17007874, PubMed:19915674). May contribute to tumor cell growth (PubMed:19915674). This isoform plays a key role in lipolysis of lipid droplets following glucose deprivation (PubMed:34077757). In response to glucose deprivation, phosphorylated by AMPK, promoting localization to lipid droplets (PubMed:34077757). Phosphorylation is followed by acetylation by KAT5, leading to dissociation of the homodimer into a monomer (PubMed:34077757). Monomeric CHKA isoform 1 is converted into a tyrosine-protein kinase, which phosphorylates lipid droplet structural proteins PLIN2 and PLIN3, leading to lipolysis of lipid droplets (PubMed:34077757).

Drugs associated with CHKA

MN58b

Target

CHKA x CHKB

Mechanism

CHKA inhibitors [+1]

Active Org.

Instituto De Investigaciones Biomédicas De Córdoba

Originator Org.

Instituto De Investigaciones Biomédicas De Córdoba

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

EB-3D

Target

CHKA

Mechanism

CHKA inhibitors

Active Org.-

Originator Org.

University Hospital Padova

Active Indication-

Inactive Indication

Refractory T Acute Lymphoblastic Leukemia

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TCD-717

Target

CHKA

Mechanism

CHKA inhibitors

Active Org.-

Originator Org.

Traslational Cancer Drugs Pharma SL

Active Indication-

Inactive Indication

Advanced Malignant Solid Neoplasm

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with CHKA

NCT01215864

/ CompletedPhase 1

A Multicenter Phase I Study of TCD-717 Given by 4-Hour Intravenous Infusion in Patients With Advanced Solid Tumors

This is a Phase I dose escalation study of TCD-717, a novel drug that is a specific inhibitor of the enzyme choline kinase alpha, in patients with advanced solid tumors. The objectives of this study are to evaluate the safety of the drug and to determine the maximum tolerated dose and appropriate dose for phase II studies. Secondary objectives are to measure the efficacy of TCD-717; and in a substudy to be conducted in the MTD confirmation cohort only, to evaluate the potential correlation between the levels of tumor choline and tumor response to the choline kinase alpha inhibitor, TCD-717, using magnetic resonance spectroscopy. Pharmacokinetics analysis will be performed on patients enrolled in the maximum tolerated dose confirmation cohort.

Start Date01 Jan 2011

Sponsor / Collaborator

Traslational Cancer Drugs Pharma SL

100 Clinical Results associated with CHKA

100 Translational Medicine associated with CHKA

0 Patents (Medical) associated with CHKA

598

Literatures (Medical) associated with CHKA

29 Apr 2025·Proceedings of the National Academy of Sciences

NAT10 exacerbates acute renal inflammation by enhancing N4-acetylcytidine modification of the CCL2/CXCL1 axis

Article

Author: Ji, Ming-lu ; Wang, Fang ; Xie, Shuai-shuai ; Hou, Chao ; Wang, Jia-nan ; Chen, Fei Xavier ; Wang, Zhi-juan ; Dong, Yu-hang ; Zhu, Qi ; Zhang, Meng-meng ; Xu, Chuan-hui ; Li, Xiang-yu ; Xu, Tao ; Zhang, Dan-feng ; Luo, Qi-chao ; Chen, Hai-yong ; Yu, Ju-tao ; Suo, Xiao-guo ; Peng, Li-jin ; Wei, Jie ; Jin, Juan ; Zhu, Sai ; Zhang, Xin-ru ; Cheng, Xin-ran ; Li, Chao ; Chen, Xin ; Meng, Xiao-ming

Inflammation plays an essential role in eliminating microbial pathogens and repairing tissues, while sustained inflammation accelerates kidney damage and disease progression. Therefore, understanding the mechanisms of the inflammatory response is vital for developing therapies for inflammatory kidney diseases like acute kidney injury (AKI), which currently lacks effective treatment. Here, we identified N-acetyltransferase 10 ( NAT10 ) as an important regulator for acute inflammation. NAT10 , the only known “writer” protein for N4-acetylcytidine (ac4C) acetylation, is elevated in renal tubules across various AKI models, human biopsies, and cultured tubular epithelial cells (TECs). Conditional knockout (cKO) of NAT10 in mouse kidneys attenuates renal dysfunction, inflammation, and infiltration of macrophages and neutrophils, whereas its conditional knock-in (cKI) exacerbates these effects. Mechanistically, our findings from ac4C-RIP-seq and RNA-seq analyses revealed that NAT10-mediated ac4C acetylation enhances the mRNA stability of a range of key chemokines, including C-C motif chemokine ligand 2 ( CCL2 ) and C-X-C motif chemokine ligand 1( CXCL1 ), promoting macrophage and neutrophil recruitment and accelerating renal inflammation. Additionally, CCL2 and CXCL1 neutralizing antibodies or their receptor inhibitors, abrogated renal inflammation in NAT10 -overexpression TECs or NAT10 -cKI mice. Importantly, inhibiting NAT10 , either through Adeno-associated virus 9 (AAV9)-mediated silencing or pharmacologically with our found inhibitor Cpd-155, significantly reduces renal inflammation and injury. Thus, targeting the NAT10/CCL2/CXCL1 axis presents a promising therapeutic strategy for treating inflammatory kidney diseases.

01 Mar 2025·Science of The Total Environment

Spatial metabolomics revealed multi-organ toxicity and visualize metabolite changes induced by borneol in zebrafish

Article

Author: Li, Chenqinyao ; Sun, Chenglong ; Zheng, Te ; Zhang, Yun ; Li, Bin ; Yang, Yanan ; Zhou, Jiashuo

This study focuses on the potential hazards of borneol (BO) to aquatic organisms and human health. BO has antibacterial, anti-inflammatory and antioxidant activities, and is widely used in medicine, cosmetics, and detergents. In this study, zebrafish was used as a model organism to systematically evaluate the effects of BO on the heart, liver, kidney, and nervous system. The effects of BO on metabolites of zebrafish were studied using MALDI-MSI. The results showed that a high concentration of BO (500 μM) could induce morphological abnormalities (swim-bladder loss, spinal curvature, body-length shortening), cardiotoxicity (decreased heart rate, increased SV-BA distance), hepatotoxicity (reduced liver area index), and neurotoxicity (impaired behavioral ability, and dopamine neuron development deficits), but there was no renal toxicity observed in zebrafish. Additionally, MALDI-MSI analysis showed that BO exposure significantly altered the levels of metabolites, including phospholipids, fatty acids, choline, and amino acids. The contents of PC-34:1, PC-34:2, PI-36:4, PE-36:1, LysoPE-22:5, LysoPC-18:1, FA-18:2, phenylalanine, lysine and glutathione were significantly increased, while the contents of PC-38:6 and PC-40:6 were significantly decreased. Notably, BO elicited a significant alteration in the mRNA expression levels of genes associated with phospholipid metabolism, fatty acid metabolism, choline metabolism, and amino acid metabolism (such as elovl5, chpt1, chka, setd7, hgd). This study revealed that BO exerted toxicity on multiple organs and demonstrated that BO causes metabolic dysregulation in zebrafish. These findings provide a novel insight into the toxicity of BO.

01 Mar 2025·Cellular Signalling

Disulfiram/Cu targeting FOXO6 modulates sensitivity of hepatocellular carcinoma to lenvatinib via disrupt choline metabolic

Article

Author: Yu, Zhijie ; Lou, Yunwei ; Tong, Songjian ; Wu, Shiyi ; Weng, Jialu ; Li, Na ; Xia, Jinglin ; Zeng, Jing ; Liao, Pan ; Pan, Yating ; Wen, Zhikai

Disulfiram/Cu(DSF/Cu) has a known pharmacokinetic and safety profile, exerting a strong antitumor effect. Oral tyrosine kinase inhibitors including lenvatinib are approved as first-line therapy for treating advanced unresectable hepatocellular carcinoma (HCC). These patients still have limited survival due to drug resistance. Disulfiram/Cu and lenvatinib are the promising antitumor treatments. In this study, we studied whether Disulfiram/Cu increased lenvatinib sensitivity in HCC cells. Moreover, the potential drug targets of Disulfiram/Cu and associated mechanisms were explored. We mainly investigated Autophagic flux was determined via immunofluorescence analysis and confocal microscopy. p-PI3K, p-AKT, p62, LC3B, FOXO6, and CHKA proteins associated with autophagy were detected by immunoblotting. In addition, antitumour activity of Disulfiram/Cu in combination with lenvatinib was examined in vivo through construction of the nude mouse transplant tumor model. Furthermore, our results show disulfiram/Cu combined with lenvatinib exerted the synergistic impact on treating HCC in vitro. Mechanistically, transcriptome combined with metabolome reveals Disulfiram/Cu targeting FOXO6 induction of autophagy mediated inhibits cell growth in hepatocellular carcinoma by downregulating CHKα for inhibiting AKT pathway activation while blocking choline metabolic reprogramming in HCC. These effects mostly explain the tumor-promoting effect of FOXO6 on HCC. In general, the results illustrate the mechanistic associations between metabolites and tumor cell malignant phenotype, contributing to developing new anti-HCC pharmacological treatments by Inhibiting FOXO6 for disrupting choline metabolic pathway.

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