更新于：2024-09-19

CHKA

更新于：2024-09-19

基本信息

别名

CHETK-alpha、CHKA、ChoKα

+ [5]

简介

Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis (PubMed:19915674, PubMed:34077757, PubMed:17007874). Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis (PubMed:19915674, PubMed:17007874). Has higher activity with choline (PubMed:19915674, PubMed:17007874). 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).

关联

项与 CHKA 相关的药物

EB-3D

靶点

CHKA

作用机制

CHKA抑制剂

在研机构

University Hospital Padova

原研机构

University Hospital Padova

在研适应症

难治性 T 急性淋巴细胞白血病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

MN58b

靶点

CHKA x CHKB

作用机制

CHKA抑制剂 [+1]

在研机构

Instituto De Investigaciones Biomédicas De Córdoba

原研机构

Instituto De Investigaciones Biomédicas De Córdoba

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

TCD-717

靶点

CHKA

作用机制

CHKA抑制剂

在研机构-

原研机构

Traslational Cancer Drugs Pharma SL

在研适应症-

非在研适应症

晚期恶性实体瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 CHKA 相关的临床试验

NCT01215864 / Completed临床1期

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.

开始日期2011-01-01

申办/合作机构

Traslational Cancer Drugs Pharma SL

100 项与 CHKA 相关的临床结果

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100 项与 CHKA 相关的转化医学

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0 项与 CHKA 相关的专利（医药）

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589

项与 CHKA 相关的文献（医药）

2024-12-01·Cellular and Molecular Life Sciences

Mfsd7b facilitates choline transport and missense mutations affect choline transport function

Article

作者: Nguyen, Long N ; Sukumar, Viresh Krishnan ; Ha, Hoa Thi Thuy ; Nguyen, Dat T ; Cazenave-Gassiot, Amaury ; Nguyen, Toan Q ; Chua, Jonathan Wei Bao ; Lim, Lina Hsiu Kim

MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.

2024-10-01·Poultry Science

Effect of myristic acid supplementation on triglyceride synthesis and related genes in the pectoral muscles of broiler chickens

Article

作者: Zhao, Guiping ; Wang, Yanke ; Liu, Xiaojing ; Guo, Yuming ; Wang, Yidong ; Wen, Jie ; Cui, Huanxian

Fatty acids (FAs) can serve as energy for poultry, maintain normal cell structure and function, and support a healthy immune system. Although the addition of polyunsaturated fatty acids (PUFAs) to the diet has been extensively studied and reported, the mechanism of action of saturated fatty acids (SFAs) remains to be elucidated. We investigated the effect of 0.04% dietary myristic acid (MA) on slaughter performance, lipid components, tissue FAs, and the transcriptome profile in chickens. The results showed that dietary MA had no effect on slaughter performance (body weight, carcass weight, eviscerated weight, and pectoral muscle weight) (P > 0.05). Dietary MA enrichment increased MA (P < 0.001) and triglycerides (TGs) (P < 0.01) levels in the pectoral muscle. The levels of palmitic acid, linoleic acid (LA), arachidonic acid (AA), SFAs, monounsaturated fatty acids (MUFAs), and PUFAs were significantly higher (P < 0.01) in the MA supplementation group compared to the control group. However, there were no significant differences in the ratios of PUFA/SFA and n6/omega-3 (n3) between the two groups. The MA content was positively correlated with the contents of palmitic acid, LA, linolenic acid (ALA), n3, n6, SFAs, and unsaturated fatty acids (UFA). DHCR24, which is known to be involved in steroid metabolism and cholesterol biosynthesis pathways, was found to be a significantly lower in the MA supplementation group compared to the control group (P < 0.05, log2(fold change) = -0.85). Five overlapping co-expressed genes were identified at the intersection between the differential expressed genes and Weighted Gene Co‑expression Network Analysis-derived hub genes associated with MA phenotype, namely BHLHE40, MSL1, PLAGL1, SRSF4, and ENSGALG00000026875. For the TG phenotype, a total of 28 genes were identified, including CHKA, KLF5, TGIF1, etc. Both sets included the gene PLAGL1, which has a negative correlation with the levels of MA and TG. This study provides valuable information to further understand the regulation of gene expression patterns by dietary supplementation with MA and examines at the molecular level the phenotypic changes induced by supplementation with MA.

2024-08-01·Advanced Science

Lipid Nanoparticle‐Mediated Delivery of CRISPR‐Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism

Article

作者: Ju, Dianwen ; Xie, Xinlei ; Deng, Yong ; Zhou, Rongrui ; Zhang, Yuanzhen ; Dou, Zihan ; Nan, Yanyang ; Sun, Yun ; Hu, Xiaozhi ; Zhu, An ; Wu, Tao ; Xu, Shuwen ; Fan, Jiajun ; Bai, Yu

AbstractNon‐alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, is reported to exacerbate hepatic steatosis in NAFLD mice and patients, indicating its probability of being a therapeutic target for NAFLD treatment. In this study, the therapeutic potential of Rubicon blockage is investigated. Lipid nanoparticles carrying Rubicon‐specific CRISPR‐Cas9 components exhibited liver accumulation, cell internalization, and Rubicon knockdown. A single administration of the nanoparticles results in attenuated lipid deposition and hepatic steatosis, with lower circulating lipid levels and decreased adipocyte size in NAFLD mice. Furthermore, the increase of phosphatidylcholine and phosphatidylethanolamine levels can be observed in the NAFLD mice livers after Rubicon silencing, along with regulatory effects on metabolism‐related genes such as CD36, Gpcpd1, Chka, and Lpin2. The results indicate that knockdown of Rubicon improves glycerophospholipid metabolism and thereby ameliorates the NAFLD progression, which provides a potential strategy for NAFLD therapy via the restoration of Rubicon.