Mechanisms that drive addiction to sugar rich foods are a major driving factor in the pathogenesis of obesity, which has become one of the most significant health care burdens. The molecular underpinnings of these hedonic mechanisms that drive addiction to sugar are poorly understood. The investigators demonstrated that methylglyoxal (MGO) derived Advanced Glycation Endproducts (AGEs) enhance food intake especially under a high sugar diet. The investigators identified a methylglyoxal (MGO) lowering cocktail, Gly-low, a combination of alpha-lipoic acid, nicotinamide, thiamine, pyridoxamine, and piperine that demonstrates a multimodal effect influencing many pathways related to aging including calorie restriction. Glycation lowering (Gly-low) treatment significantly reduces food intake and weight gain in the db/db mice that lack the leptin receptor. The investigators also extended the lifespan of C57BL/6 mice fed with these compounds starting when they were 24 months old. Based on these results, the investigators hypothesized that methylglyoxal (MGO) lowering cocktail of compounds can be given to adults with obesity, specified as body mass index (BMI) >27, to lower serum and urinary markers of insulin resistance, lower boy mass index (BMI), and lower food intake.

开始日期2024-12-01

申办/合作机构

The University of California, San Francisco

NL-OMON56635 / RecruitingN/AIIT

The effect of pyridoxamine supplementation on microvascular function in type 2 diabetes: a double-blind randomized placebo-controlled cross-over trial - PYRAMID trial

开始日期2024-05-17

申办/合作机构-

JPRN-jRCTs031220256 / Recruiting临床2/3期IIT

Explorative study on the effects of pyridoxamine in patients with menopausal disorder with psychological symptoms

开始日期2023-10-19

申办/合作机构-

100 项与 Advanced glycation end product 相关的临床结果

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100 项与 Advanced glycation end product 相关的转化医学

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0 项与 Advanced glycation end product 相关的专利（医药）

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项与 Advanced glycation end product 相关的文献（医药）

2024-10-01·Biomaterials Advances

Simultaneous regulation of AGE/RAGE signaling and MMP-9 expression by an immunomodulating hydrogel accelerates healing in diabetic wounds

Article

作者: Sheikh, Parvaiz A ; Kumar, Ashok ; Koul, Veena ; Singh, Prerna ; Banerjee, Ahana ; Bhattacharyya, Jayanta

PURPOSEIn chronic hyperglycemia, the advanced glycation end product (AGE) interacts with its receptor (RAGE) and contributes to impaired wound healing by inducing oxidative stress, generating dysfunctional macrophages, and prolonging the inflammatory response. Additionally, uncontrolled levels of proteases, including metallomatrix protease-9 (MMP-9), in the diabetic wound bed degrade the extracellular matrix (ECM) and biological cues that augment healing. A multifunctional antimicrobial hydrogel (Immuno-gel) containing RAGE and MMP-9 inhibitors can regulate the wound microenvironment and promote scar-free healing.RESULTSImmuno-gel was characterized and the wound healing efficacy was determined in vitro cell culture and in vivo diabetic Wistar rat wound model using ELISA, Western blot, and Immunofluorescence staining. The Immuno-gel exhibited a highly porous morphology with excellent in vitro cytocompatibility. AGE-stimulated macrophages treated with the Immuno-gel released higher levels of pro-healing cytokines in vitro. In the hydrogel-wound interface of diabetic Wistar rats, Immuno-gel treatment significantly reduced MMP-9 and NF-κB expression and enhanced pro-healing (M2) macrophage population and pro-healing cytokines.CONCLUSIONAltogether, this study suggests that Immuno-gel simultaneously attenuates macrophage dysfunction through the inhibition of AGE/RAGE signaling and reduces MMP-9 overexpression, both of which favor scar-free healing. The combinatorial treatment with RAGE and MMP-9 inhibitors via Immuno-gel simultaneously modulates the diabetic wound microenvironment, making it a promising novel treatment to accelerate diabetic wound healing.

2024-09-01·European Journal of Clinical Investigation

Soluble receptor of advanced glycation end product as a biomarker in neurocognitive and neuropsychiatric disorders: A meta‐analysis of controlled studies

Review

作者: Jazayeri, Shima ; Fatahi, Somaye ; Jamshidi, Sanaz ; Zaroudi, Marsa ; Nameni, Ghazaleh

AbstractBackground & ObjectivesCurrently, there is a significant focus on the decrease of soluble receptor of advanced glycation end products (sRAGE) in neurocognitive and neuropsychiatric disorders. sRAGE plays a decoy role against the inflammatory response of advanced glycation end products (AGE), which has led to increased interest in its role in these disorders. This meta‐analysis aimed to investigate the significant differences in sRAGE levels between neurocognitive and neuropsychiatric disorders compared to control groups.MethodA systematic review was conducted using the PUBMED, Scopus and Embase databases up to October 2023. Two reviewers assessed agreement for selecting papers based on titles and abstracts, with kappa used to measure agreement and finally publications were scanned according to controlled studies. Effect sizes were calculated as weighted mean differences (WMD) and pooled using a random effects model. Heterogeneity was assessed using I2, followed by subgroup analysis and meta‐regression tests. Quality assessment was performed using the Newcastle‐Ottawa Quality Assessment Scale.ResultsIn total, 16 studies were included in the present meta‐analysis. Subjects with neurocognitive (n = 1444) and neuropsychiatric (n = 444) disorders had lower sRAGE levels in case–control (WMD: −0.21, 95% CI: −0.33, −0.10; p <.001) and cross‐sectional (WMD: −0.29, 95% CI = −0.44, −0.13, p <.001) studies with high heterogeneity and no publication bias. In subgroup analysis, subjects with cognitive impairment (WMD: −0.87, 95% CI: −1.61, −0.13, p =.000), and age >50 years (WMD: −0.39, 95% CI: −0.74, −0.05, p =.000), had lower sRAGE levels in case–control studies. Also, dementia patients (WMD: −0.41, 95% CI: −0.72, −0.10, p =.014) with age >50 years (WMD: −0.33, 95% CI: −0.54, −0.13, p = 0.000) and in Asian countries (WMD: −0.28, 95% CI: −0.42, −0.13, p =.141) had lower sRAGE levels in cross‐sectional studies.ConclusionThis meta‐analysis revealed a significant reduction in sRAGE in neurocognitive and neuropsychiatric disorders particularly in Asians and moderate age.

2024-07-19·Medicine

Exploring the mechanisms of Guizhifuling pills in the treatment of coronary spastic angina based on network pharmacology combined with molecular docking

Article

作者: Zhao, Yang ; Wang, Yanhong ; Cui, Weiqi ; Xu, Shuaimin ; Song, Weijuan ; Zhang, Xiangyu

Coronary spastic angina (CSA) is common, and treatment options for refractory vasospastic angina are sometimes limited. Guizhifuling pills (GFP) have demonstrated efficacy in reducing CSA episodes, but their pharmacological mechanism remains unclear. To explore the mechanism of action of GFP in preventing and treating CSA, we employed network pharmacology and molecular docking to predict targets and analyze networks. We searched GFP chemical composition information and related targets from databases. The drug-target and drug-target pathway networks were constructed using Cytoscape. Then the protein–protein interaction was analyzed using the STRING database. Gene Ontology biological functions and Kyoto Encyclopedia of Genes and Genomes pathways were performed by the Metascape database, and molecular docking validation of vital active ingredients and action targets of GFP was performed using AutoDock Vina software. The 51 active components in GFP are expected to influence CSA by controlling 279 target genes and 151 signaling pathways. Among them, 6 core components, such as quercetin, β-sitosterol, and baicalein, may regulate CSA by affecting 10 key target genes such as STAT3, IL-6, TP53, AKT1, and EGFR. In addition, they are involved in various critical signaling pathways such as apelin, calcium, advanced glycation end product–receptor for advanced glycation end product, and necroptosis. Molecular docking analysis confirms favorable binding interactions between the active components of GFP and the selected target proteins. The effects of GFP in treating CSA involve multiple components, targets, and pathways, offering a theoretical basis for its clinical use and enhancing our understanding of how it works.

项与 Advanced glycation end product 相关的新闻（医药）

2023-06-15

·PRNewswire

CANTEX PHARMACEUTICALS TO PRESENT AT THE MEDINVEST ONCOLOGY INVESTOR CONFERENCE IN BOSTON

WESTON, Fla., June 15, 2023 /PRNewswire/ -- Cantex Pharmaceuticals, Inc., a clinical-stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed, today announced that it will present at the MedInvest Oncology Investor Conference being held June 21-22, 2023, in Boston, MA. Stephen G. Marcus, M.D. Cantex's Chief Executive Officer, will present a corporate overview to strategics/big Pharma, VCs, family offices, hedge funds, and government/non-profit grant makers on Thursday, June 22 at 11:10 a.m. ET, at the offices of Goodwin Procter LLP, 100 Northern Ave., Boston, MA 02210, 17th Floor. Dr. Marcus will also be available for one-on-one meetings at the conference. Those interested in meeting with Cantex can register using the conference website: or by requesting a meeting through any of the contacts below. About Azeliragon Azeliragon is an orally administered capsule, taken once daily, that inhibits interactions of the receptor for advanced glycation endproducts (known as RAGE) with certain ligands, including HMGB1 and S100 proteins in the tumor microenvironment. Azeliragon was originally under development for Alzheimer's disease by vTv Therapeutics Inc. (NASDAQ: VTVT) from which Cantex licensed worldwide rights to azeliragon. Clinical safety data from these trials, involving more than 2000 individuals dosed for periods up to 18 months, indicate that azeliragon is very well tolerated. Cantex has ongoing clinical trials in metastatic pancreatic cancer, neoadjuvant therapy of breast cancer, and hospitalized COVID patients to prevent acute kidney injury, and will soon initiate FDA-approved phase 2 clinical trials of azeliragon in newly diagnosed glioblastoma, and in brain metastases in combination with stereotactic radiosurgery. These trials are based on robust pre-clinical data as well as the extensive clinical safety information from randomized placebo-controlled clinical trials. About Cantex Pharmaceuticals, Inc. Cantex Pharmaceuticals, Inc. is a privately held, clinical-stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed. For more information, please visit . Contact: Tiberend Strategic Advisors, Inc. Investors Daniel Kontoh-Boateng +1 862-213-1398 [email protected] Media Casey McDonald +1 646-577-8520 [email protected] Cantex Pharmaceuticals, Inc. Stephen G. Marcus, M.D. +1 954-315-3660 [email protected] Juan F. Rodriguez +1 954-315-3660 [email protected] SOURCE Cantex Pharmaceuticals, Inc.

临床2期

2023-06-01

·PRNewswire

CANTEX PHARMACEUTICALS OBTAINS EXCLUSIVE WORLDWIDE RIGHTS TO INTELLECTUAL PROPERTY FROM GEORGETOWN UNIVERSITY FOR AZELIRAGON AS A POTENTIAL TREATMENT OF CANCER-RELATED COGNITIVE DECLINE

Cantex to Expand Collaboration with Georgetown's Lombardi Comprehensive Cancer Center WESTON, Fla., June 1, 2023 /PRNewswire/ -- Cantex Pharmaceuticals, Inc., a clinical-stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed, today announced that it has obtained an exclusive worldwide license from Georgetown University for intellectual property related to the potential use of azeliragon to treat, prevent or alleviate cancer-treatment related cognitive decline. This exclusive worldwide license expands Cantex's existing robust azeliragon composition of matter patent, its overall intellectual property portfolio and additional regulatory exclusivities. Cancer-related cognitive decline involves problems with memory, attention, concentration, and executive functioning that may result from some cancer treatments. This condition commonly occurs in women receiving intensive neoadjuvant chemotherapy to reduce the size of a breast cancer prior to surgery. Pre-clinical studies performed at Georgetown's Lombardi Comprehensive Cancer Center suggest clinical investigation is warranted to explore the potential for azeliragon to treat, prevent or alleviate cognitive symptoms, sometimes referred to as "chemo-brain", that are associated with cancer chemotherapy. Pre-clinical studies at Georgetown have also identified a striking anti-metastatic effect of azeliragon in animal models of triple-negative breast cancer, suggesting that azeliragon should also be investigated for the potential benefit of reducing the risk of metastatic breast cancer. Georgetown is currently enrolling patients in a pilot clinical trial of Cantex's azeliragon in women with breast cancer receiving neoadjuvant chemotherapy. "Neoadjuvant chemotherapy has made a critically important contribution to the curative treatment of early breast cancer. Side effects of this treatment, including cognitive disturbances, can be debilitating, significantly impairing activities of daily life. Although neoadjuvant chemotherapy combined with surgery is potentially curative, local recurrence and metastasis can occur. With the clinical trial in progress at Georgetown, and subsequent randomized studies, Cantex's collaboration with Georgetown seeks to understand if azeliragon can alleviate cognitive decline caused by chemotherapy," said Stephen Marcus, M.D., CEO of Cantex. Marc Lippman, M.D., MACP FRCP, Professor of Oncology, Co-Director of the Breast Cancer Program at the Lombardi Comprehensive Cancer Center at Georgetown University, commented: "Speaking on behalf of my many colleagues and collaborators at Georgetown, we are pleased that our pre-clinical findings warrant clinical study of Cantex's azeliragon to see if it can prevent or mitigate cancer treatment-related cognitive decline, while reducing the risk of metastasis. Through this collaboration with Cantex, we are eager to see this therapy move toward definitive randomized controlled clinical trials." Marc Lippman is a co-inventor on a patent application that has been filed by Georgetown University related to the technology described. About Azeliragon Azeliragon is an orally administered capsule, taken once daily, that inhibits interactions of the receptor for advanced glycation endproducts (known as RAGE) with certain ligands, including HMGB1 and S100 proteins in the tumor microenvironment. Azeliragon was originally under development for Alzheimer's disease by vTv Therapeutics Inc. (NASDAQ: VTVT) from which Cantex licensed worldwide rights to azeliragon. Clinical safety data from these trials, involving more than 2000 individuals dosed for periods up to 18 months, indicate that azeliragon is very well tolerated. Cantex has ongoing clinical trials in metastatic pancreatic cancer, neoadjuvant therapy of breast cancer, and hospitalized COVID patients to prevent acute kidney injury, and will soon initiate FDA-approved phase 2 clinical trials of azeliragon in newly diagnosed glioblastoma, and in brain metastases in combination with stereotactic radiosurgery. These trials are based on robust pre-clinical data as well as the extensive clinical safety information from randomized placebo-controlled clinical trials. About Cantex Pharmaceuticals, Inc. Cantex Pharmaceuticals, Inc. is a privately held, clinical-stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed. For more information, please visit . Contact Data: Tiberend Strategic Advisors, Inc. Investors Daniel Kontoh-Boateng (862) 213-1398 [email protected] Media Casey McDonald +1 646-577-8520 [email protected] Cantex Pharmaceuticals, Inc. Stephen G. Marcus, M.D. +1 954-315-3660 [email protected] Juan F. Rodriguez +1 954-315-3660 [email protected] SOURCE Cantex Pharmaceuticals, Inc.

引进/卖出临床2期