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Last update 08 May 2025

CUTC

Last update 08 May 2025

Basic Info

Synonyms

CGI-32, Copper homeostasis protein cutC homolog, CUTC

+ [1]

Introduction

May play a role in copper homeostasis. Can bind one Cu(1+) per subunit.

Drugs associated with CUTC

ZTx102

Target

CUTC

Mechanism

CUTC blockers

Active Org.

Zehna Therapeutics, Inc.

Originator Org.

Zehna Therapeutics, Inc.

Active Indication

Chronic Kidney Diseases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CUTC

100 Translational Medicine associated with CUTC

0 Patents (Medical) associated with CUTC

Literatures (Medical) associated with CUTC

01 Jan 2025·Clinical Nutrition

Association of trimethylamine N-oxide and metabolites with kidney function decline in patients with chronic kidney disease

Article

Author: Lin, Ting-Yun ; Hung, Szu-Chun ; Cheng, Evelyn

BACKGROUNDTrimethylamine N-oxide (TMAO) is a gut microbial metabolite derived from dietary l-carnitine and choline. High plasma TMAO levels are associated with cardiovascular disease and overall mortality, but little is known about the associations of TMAO and related metabolites with the risk of kidney function decline among patients with chronic kidney disease (CKD).METHODSWe prospectively followed 152 nondialysis patients with CKD stages 3-5 and measured plasma TMAO and related metabolites (trimethylamine [TMA], choline, carnitine, and γ-butyrobetaine) via liquid chromatography‒mass spectrometry. An estimated glomerular filtration rate (eGFR) slope >3 ml/min/per 1.73 m² per year was defined as a rapid decline. We performed logistic regression to determine the probability of rapid or slow eGFR decline, with each metabolite as the main predictor. The gut microbiota was profiled via whole metagenomic sequencing.RESULTSThe participants had a median age of 66 years, 41.4 % were women, 39.5 % had diabetes, and the median eGFR was 23 mL/min/1.73 m². A rapid decrease in the eGFR occurred in 65 patients (42.8 %) over a median follow-up of 3.3 years. After adjustment for baseline eGFR, proteinuria, and clinical factors, plasma TMAO levels were independently associated with increased odds of rapid eGFR decline (odds ratio, 2.42; 95 % CI, 1.36-4.32), whereas plasma TMA, choline, carnitine, and γ-butyrobetaine levels were not. Patients who exhibited rapid eGFR decline had a distinct gut microbial composition characterized by increased α-diversity and an abundance of TMA-producing bacteria, including those of the genera Desulfovibrio and Collinsella tanakaei, as well as increased expression of the TMA-producing enzymes bbuA and cutC.CONCLUSIONOur findings suggest the relevance of plasma TMAO in the progression of kidney disease among patients with CKD.

01 Oct 2024·Environmental Research

Potential effects of Cu2+ stress on nitrogen removal performance, microbial characteristics, and metabolism pathways of biofilm reactor

Article

Author: Dong, Wenyi ; Huang, Xiao ; Hu, Liangshan ; Zhou, Guorun ; Zhang, Shuai ; Wang, Hongjie ; Zheng, Zhihao

Sequencing batch biofilm reactors (SBBR) were utilized to investigate the impact of Cu²⁺ on nitrogen (N) removal and microbial characteristics. The result indicated that the low concentration of Cu²⁺ (0.5 mg L^-1) facilitated the removal of ammonia nitrogen (NH₄⁺-N), total nitrogen (TN), nitrate nitrogen (NO₃^--N), and chemical oxygen demand (COD). In comparison to the average effluent concentration of the control group, the average effluent concentrations of NH₄⁺-N, NO₃^--N, COD, and TN were found to decrease by 40.53%, 17.02%, 10.73%, and 15.86%, respectively. Conversely, the high concentration of Cu²⁺ (5 mg L^-1) resulted in an increase of 94.27%, 55.47%, 22.22%, and 14.23% in the aforementioned parameters, compared to the control group. Low concentrations of Cu²⁺ increased the abundance of nitrifying bacteria (Rhodanobacter, unclassified-o-Sacharimonadales), denitrifying bacteria (Thermomonas, Comamonas), denitrification-associated genes (hao, nosZ, norC, nffA, nirB, nick, and nifD), and heavy-metal-resistant genes related to Cu²⁺ (pcoB, cutM, cutC, pcoA, copZ) to promote nitrification and denitrification. Conversely, high concentration Cu²⁺ hindered the interspecies relationship among denitrifying bacteria genera, nitrifying bacteria genera, and other genera, reducing denitrification and nitrification efficiency. Cu²⁺ involved in the N and tricarboxylic acid (TCA) cycles, as evidenced by changes in the abundance of key enzymes, such as (EC:1.7.99.1), (EC:1.7.2.4), and (EC:1.1.1.42), which initially increased and then decreased with varying concentrations of Cu²⁺. Conversely, the abundance of EC1.7.2.1, associated with the accumulation of nitrite nitrogen (NO₂^--N), gradually declined. These findings provided insights into the impact of Cu²⁺ on biological N removal.

01 Jul 2024·Current Medicinal Chemistry

Berberine Decreases Thrombosis Potential Induced by a High-choline Diet by Inhibiting CutC Enzyme

Article

Author: Zhao, Yi-han ; Gao, Zhu-ye ; Shi, Da-zhuo ; Gao, Jie ; Qu, Hua ; Zhang, Ying ; Shi, Jun-he

Introduction:Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear.Objective:The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it.Methods:C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl3 injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays.Result:The results showed that berberine increased the carotid artery occlusion time following FeCl3 injury and decreased the platelet hyperresponsiveness induced by a high-- choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme.Conclusion:Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.

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