Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Uremic toxins such as 4-Decenal are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类无致癌性(未列入国际癌症研究机构IARC清单)。
No indication of carcinogenicity to humans (not listed by IARC).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
健康影响
长期暴露于尿毒症毒素可能会导致多种疾病,包括肾脏损伤、慢性肾病和心血管疾病。
Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.
Alkenyl Carbonyl Derivatives in Enantioselective Redox Relay Heck Reactions: Accessing α,β-Unsaturated Systems
摘要:
A highly enantioselective and site-selective Pd-catalyzed arylation of alkenes linked to carbonyl derivatives to yield alpha,beta-unsaturated systems is reported. The high site selectivity is attributed to both a solvent effect and the polarized nature of the carbonyl group, both of which have been analyzed through multidimensional analysis tools. The reaction can be performed in an iterative fashion allowing for a diastereoselective installation of two aryl groups along an alkyl chain.
Synthesis of (4E,6Z,10Z)-hexadeca-4,6,10-trien-1-ol and (4E,6E,10Z)-hexadeca-4,6,10-trien-1-ol, the pheromone components of cocoa pod borer moth Conopomorpha cramerella
作者:Fei Huang、Yushun Zhang、Yun Yao、Wanqiu Yang、Yunhai Tao
DOI:10.1039/c7ra04027j
日期:——
A concise and efficient synthesis of the pheromone components of the cocoa pod borer moth, namely (4E,6Z,10Z)-hexadeca-4,6,10-trien-1-ol and (4E,6E,10Z)-hexadeca-4,6,10-trien-1-ol, starting from commercially available materials, was reported. The overall yield was 30.4% and 27.4%, respectively. The stereoselective formation of (E,Z)- or (E,E)-conjugated double bond relied on Sonogashiracoupling with
The Ras Pathway Modulator Melophlin A Targets Dynamins
作者:Tanja Knoth、Karin Warburg、Catherine Katzka、Amrita Rai、Alexander Wolf、Andreas Brockmeyer、Petra Janning、Thomas F. Reubold、Susanne Eschenburg、Dietmar J. Manstein、Katja Hübel、Markus Kaiser、Herbert Waldmann
DOI:10.1002/anie.200902023
日期:2009.9.14
combination of organic synthesis, chemical proteomics, biophysics, and cell and molecular biology investigations reveals that the natural product melophlin A (purple) influences signal propagation through the Ras network by interfering with the function of dynamins (green) in endocytosis.
A Transition-Metal-Free One-Pot Cascade Process for Transformation of Primary Alcohols (RCH<sub>2</sub>
OH) to Nitriles (RCN) Mediated by SO<sub>2</sub>
F<sub>2</sub>
作者:Ying Jiang、Bing Sun、Wan-Yin Fang、Hua-Li Qin
DOI:10.1002/ejoc.201900478
日期:2019.6.2
A new transition‐metal‐free one‐pot cascade process for the direct conversion of alcohols to nitriles was developed without introducing an “additional carbon atom”. This protocol allows transformations of readily available, inexpensive, and abundant alcohols to highly valuable nitriles.
Design, Synthesis, and Biological Evaluation of the Combinatorial Library with a New Spirodiketopiperazine Scaffold. Discovery of Novel Potent and Selective Low-Molecular-Weight CCR5 Antagonists
anti-HIV activity. Herein, we describe in detail the identification of these lead compounds using a combinatorial chemistry approach. A novel spirodiketopiperazine scaffold was designed on the basis of the concept of the privileged structure of G-protein-coupled receptors (GPCRs). This new framework was obtained in acceptable yield with high purity from the readily prepared isonitrile resin through
[EN] PYRROL-1 -YL BENZOIC ACID DERIVATES USEFUL AS MYC INHIBITORS<br/>[FR] DÉRIVÉS D'ACIDE PYRROL-1-YL-BENZOÏQUE UTILES EN TANT QU'INHIBITEURS DE MYC
申请人:DANA FARBER CANCER INST INC
公开号:WO2014071247A1
公开(公告)日:2014-05-08
The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors.