Chemical, Biochemical, and Biological Behaviors of Vanadate and Its Oligomers

Wang, Kui

doi:10.1007/978-3-642-41004-8_1

Cited by 4 publications

(3 citation statements)

References 96 publications

(101 reference statements)

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“…As shown in Table , compared to the wild-type enzymes, hCDC14A F48A and hCDC14B F85A mutants displayed reduced sensitivity toward compound 15 , resulting in IC 50 values that were 27.3- and 15.6-fold higher, respectively. To ascertain that this diminished effectiveness of compound 15 could be attributed to the absence of the π–π interaction, we also assessed the IC 50 of vanadate (a known general phosphate mimicking PTP competitive inhibitor , ), PhFP, and compound 9 (both PhFP and compound 9 are not supposed to engage the P+1 pocket) for the hCDC14A F48A and hCDC14B F85A mutants. As anticipated, the IC 50 values of these compounds for the hCDC14A F48A and hCDC14B F85A mutants were comparable to those observed with the corresponding wild-type enzymes (data shown in Table S2).…”

Section: Resultsmentioning

confidence: 99%

Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases

Dong,

Jassim,

Milholland

et al. 2024

J. Med. Chem.

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Together with protein tyrosine kinases, protein tyrosine phosphatases (PTPs) control protein tyrosine phosphorylation and regulate numerous cellular functions. Dysregulated PTP activity is associated with the onset of multiple human diseases. Nevertheless, understanding of the physiological function and disease biology of most PTPs remains limited, largely due to the lack of PTP-specific chemical probes. In this study, starting from a well-known nonhydrolyzable phosphotyrosine (pTyr) mimetic, phosphonodifluoromethyl phenylalanine (F2Pmp), we synthesized 7 novel phosphonodifluoromethyl-containing bicyclic/ tricyclic aryl derivatives with improved cell permeability and potency toward various PTPs. Furthermore, with fragment-and structure-based design strategies, we advanced compound 9 to compound 15, a first-in-class, potent, selective, and bioavailable inhibitor of human CDC14A and B phosphatases. This study demonstrates the applicability of the fragment-based design strategy in creating potent, selective, and bioavailable PTP inhibitors and provides a valuable probe for interrogating the biological roles of hCDC14 phosphatases and assessing their potential for therapeutic interventions.

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Section: Resultsmentioning

confidence: 99%

Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases

Dong,

Jassim,

Milholland

et al. 2024

J. Med. Chem.

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“…However, rats all died when they received vanadyl sulfate for more than 2 mM/kg of their body weight [ 83 ]. The biological effects are different according to the species of vanadium compounds [ 84 ]; the toxicities of vanadium in different oxidation states were divergent as well. Studies have illustrated that the highest oxidated valence (+5) of vanadium was the most toxic state [ 85 ].…”

Section: The Advance Of Applying Vanadium In Ad Treatmentmentioning

confidence: 99%

The Deficits of Insulin Signal in Alzheimer’s Disease and the Mechanisms of Vanadium Compounds in Curing AD

Yao,

He,

You

et al. 2023

CIMB

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Vanadium is a well-known essential trace element, which usually exists in oxidation states in the form of a vanadate cation intracellularly. The pharmacological study of vanadium began with the discovery of its unexpected inhibitory effect on ATPase. Thereafter, its protective effects on β cells and its ability in glucose metabolism regulation were observed from the vanadium compound, leading to the application of vanadium compounds in clinical trials for curing diabetes. Alzheimer’s disease (AD) is the most common dementia disease in elderly people. However, there are still no efficient agents for treating AD safely to date. This is mainly because of the complexity of the pathology, which is characterized by senile plaques composed of the amyloid-beta (Aβ) protein in the parenchyma of the brain and the neurofibrillary tangles (NFTs), which are derived from the hyperphosphorylated tau protein in the neurocyte, along with mitochondrial damage, and eventually the central nervous system (CNS) atrophy. AD was also illustrated as type-3 diabetes because of the observations of insulin deficiency and the high level of glucose in cerebrospinal fluid (CSF), as well as the impaired insulin signaling in the brain. In this review, we summarize the advances in applicating the vanadium compound to AD treatment in experimental research and point out the limitations of the current study using vanadium compounds in AD treatment. We hope this will help future studies in this field.

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“…In addition, it was found that elevated vanadium uptake could affect cholesterol and triglyceride metabolism, and stimulate hepatic glucose oxidation and glycogen synthesis [ 27 ]. However, the toxicity of vanadium was also observed in animal experiments [ 28 , 29 ], though the biological effects may be different dependent on the species of vanadium compounds formed in the biological media [ 30 ]. Rats would all die when they were treated with vanadyl sulfate at levels greater than 2 mM V kg −1 body weight [ 31 ].…”

Section: The Pharmacological Research Of Vanadium Compounds In Treating Diabetesmentioning

confidence: 99%

Alzheimer’s Disease and Diabetes Mellitus in Comparison: The Therapeutic Efficacy of the Vanadium Compound

You

Liu

et al. 2021

IJMS

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Alzheimer’s disease (AD) is an intractable neurodegenerative disease that leads to dementia, primarily in elderly people. The neurotoxicity of amyloid-beta (Aβ) and tau protein has been demonstrated over the last two decades. In line with these findings, several etiological hypotheses of AD have been proposed, including the amyloid cascade hypothesis, the oxidative stress hypothesis, the inflammatory hypothesis, the cholinergic hypothesis, et al. In the meantime, great efforts had been made in developing effective drugs for AD. However, the clinical efficacy of the drugs that were approved by the US Food and Drug Association (FDA) to date were determined only mild/moderate. We recently adopted a vanadium compound bis(ethylmaltolato)-oxidovanadium (IV) (BEOV), which was originally used for curing diabetes mellitus (DM), to treat AD in a mouse model. It was shown that BEOV effectively reduced the Aβ level, ameliorated the inflammation in brains of the AD mice, and improved the spatial learning and memory activities of the AD mice. These finding encouraged us to further examine the mechanisms underlying the therapeutic effects of BEOV in AD. In this review, we summarized the achievement of vanadium compounds in medical studies and investigated the prospect of BEOV in AD and DM treatment.

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Chemical, Biochemical, and Biological Behaviors of Vanadate and Its Oligomers

Cited by 4 publications

References 96 publications

Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases

Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases

The Deficits of Insulin Signal in Alzheimer’s Disease and the Mechanisms of Vanadium Compounds in Curing AD

Alzheimer’s Disease and Diabetes Mellitus in Comparison: The Therapeutic Efficacy of the Vanadium Compound

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