Novel therapeutics for diabetic micro- and macrovascular complications.

Abstract:

:Diabetic patients have a two- to four-fold increased risk for the development of microvascular (renal, neuronal and retinal) and macrovascular complications. Unfortunately, these complications may develop in both Type 1 and Type 2 diabetic patients even with careful glycaemic, blood pressure and lipid control. With the worldwide increase in the incidence diabetes, new strategies to prevent the complications are urgently needed. Mediators of vascular damage of diabetes include poor glycemic control, lipoprotein abnormalities, hypertension, oxidative stress, inflammation and advanced glycation end-products (AGEs), which are modified proteins formed by non-enzymatic glycation. AGEs are resistant to enzymatic degradation and therefore very stable, thus their accumulation continues throughout aging. AGE accumulation causes arterial stiffening in the vessel wall, glomerulosclerosis in the kidney, and vascular hyperpermeability in the retina. Through their interaction with their putative receptor the so-called receptor for AGEs (RAGE), AGEs activate endothelial cells and macrophages, generate reactive oxygen species (ROS), induce overexpression of vascular endothelial growth factor (VEGF) and vascular cell adhesion molecule-1 (VCAM-1), and quench nitric oxide (NO). The pharmacological treatment currently available for either Type 1 or Type 2 diabetic patients does not directly address the excess accumulation of AGEs. Novel compounds that inhibit AGE formation, cleave AGE cross-links or reverse their interaction with RAGE are now accessible and could prove useful in meeting this challenge. Other strategies such as inhibition of the hexosamine pathway, vitamin therapy to reduce oxidation and AGE accumulation, reduction of the ROS, or blocking the actions of growth factors or intracellular messengers of cell differentiation are also currently under research. This review will recount recent advances in the development of therapeutic approaches for inhibiting and treating the development of diabetic end-organ damage.

journal_name

Curr Med Chem

authors

Soro-Paavonen A,Forbes JM

doi

10.2174/092986706777452515

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

1777-88

issue

15

eissn

0929-8673

issn

1875-533X

journal_volume

13

pub_type

杂志文章,评审
  • Small Molecules as Drugs to Upregulate Metastasis Suppressors in Cancer Cells.

    abstract::It is well-recognized that the majority of cancer-related deaths is attributed to metastasis, which can arise from virtually any type of tumor. Metastasis is a complex multistep process wherein cancer cells must break away from the primary tumor, intravasate into the circulatory or lymphatic systems, extravasate, prol...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867325666180522090842

    authors: Wong KM,Song J,Saini V,Wong YH

    更新日期:2019-01-01 00:00:00

  • The Role of (Modified) Lipoproteins in Vascular Function: A Duet Between Monocytes and the Endothelium.

    abstract::Over the last century, many studies have demonstrated that low-density lipoprotein (LDL) is a key risk factor of cardiovascular diseases (CVD) related to atherosclerosis. Thus, for these CVD patients, LDL lowering agents are commonly used in the clinic to reduce the risk for CVD. LDL, upon modification, will develop d...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867325666180316121015

    authors: Schnitzler JG,Dallinga-Thie GM,Kroon J

    更新日期:2019-01-01 00:00:00

  • Vasoactive compounds in the neonatal period.

    abstract::Sufficient organ blood flow of healthy newborn babies is maintained by relatively low systemic blood pressure. Premature infants are at an increased risk of systemic hypotension, often but not obviously, resulting in hypoperfusion of the cerebral, renal and intestinal vascular beds. Maintaining a stable blood pressure...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986712803306330

    authors: Toth-Heyn P,Cataldi L

    更新日期:2012-01-01 00:00:00

  • 3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas.

    abstract::Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failu...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867326666191212162102

    authors: Heredia-Soto V,Redondo A,Kreilinger JJP,Martínez-Marín V,Berjón A,Mendiola M

    更新日期:2020-01-01 00:00:00

  • Discovery and Development of the Oral Complement Factor D Inhibitor Danicopan (ACH-4471).

    abstract::Complement plays a vital role in our innate immune defense against invasive microorganisms. Excessive complement activation or insufficient control of activation on host cells, however, is associated with several chronic disorders. Essential to the activation and amplification of the Alternative Pathway (AP) of comple...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867326666191001130342

    authors: Wiles JA,Galvan MD,Podos SD,Geffner M,Huang M

    更新日期:2020-01-01 00:00:00

  • Effects of Resveratrol and Other Polyphenols on the Most Common Brain Age-Related Diseases.

    abstract:BACKGROUND:With global increase in elderly population, modern societies must find strategies to reduce the consequences of aging process; thereby decreasing the incidence of age-related neurodegenerative diseases. Oxidative stress and recently inflammation, have been pointed out as the leading causes of brain aging. Th...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867324666170724102743

    authors: Sarubbo F,Moranta D,Asensio VJ,Miralles A,Esteban S

    更新日期:2017-01-01 00:00:00

  • Regulators of serine/threonine protein phosphatases at the dawn of a clinical era?

    abstract::Reversible phosphorylation is a key mechanism for regulating the biological activity of many human proteins that affect a diverse array of cellular processes, including protein-protein interactions, gene transcription, cell-cycle progression and apoptosis. Once viewed as simple house keeping enzymes, recent studies ha...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867023368836

    authors: Honkanen RE,Golden T

    更新日期:2002-11-01 00:00:00

  • Fighting tumor cell survival: advances in the design and evaluation of Pim inhibitors.

    abstract::The Pim (provirus insertion site of Moloney murine leukemia virus) family of serine/threonine protein kinases possesses the fundamental characteristics critical for the biology of eukaryotes, in particular, survival and malignant transformation of cells. The members of this protein family (Pim-1 to Pim-3) are aberrant...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986710793348554

    authors: Anizon F,Shtil AA,Danilenko VN,Moreau P

    更新日期:2010-01-01 00:00:00

  • Recent advances in non-peptidomimetic dipeptidyl peptidase 4 inhibitors: medicinal chemistry and preclinical aspects.

    abstract::Dipeptidyl peptidase 4 (DPP-4), a substrate-specific serine protease, has been validated as a promising drug target for the treatment of type 2 diabetes. DPP-4 inhibitors significantly lowered blood glucose levels in patients with type 2 diabetes without common body weight gain, hypoglycemia and gastrointestinal distu...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986712802002491

    authors: Liu Y,Hu Y,Liu T

    更新日期:2012-01-01 00:00:00

  • Snake Venom: From Deadly Toxins to Life-saving Therapeutics.

    abstract::Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and cause notable mortality throughout the world. The venom constitutes families of proteins and peptides with various isoforms that make it a cocktail of di...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867324666170605091546

    authors: Waheed H,Moin SF,Choudhary MI

    更新日期:2017-01-01 00:00:00

  • Updates on Managing Type 2 Diabetes Mellitus with Natural Products: Towards Antidiabetic Drug Development.

    abstract::Over the years, natural products have shown success as antidiabetics in in vitro, in vivo studies and clinical trials. Because natural product-derived drugs are more affordable and effective with fewer side-effects compared to conventional therapies, pharmaceutical research is increasingly leaning towards the discover...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867323666160813222436

    authors: Alam F,Islam MA,Kamal MA,Gan SH

    更新日期:2018-01-01 00:00:00

  • The chemical biology of immunophilin ligands.

    abstract::The immunophilin ligands cyclosporin A, FK506 and rapamycin are best known for their immunosuppressive properties and their clinical use in transplantation medicine. These compounds or their analogs are also clinically used or investigated in various types of cancer, coronary angioplasty, dermatology, hepatitis C infe...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986711798194342

    authors: Gaali S,Gopalakrishnan R,Wang Y,Kozany C,Hausch F

    更新日期:2011-01-01 00:00:00

  • Development of DNA topoisomerase II-mediated anticancer agents, 3-(9-acridinylamino)-5-hydroxymethylanilines (AHMAs) and related compounds.

    abstract::A series of potential topoisomerase II-mediated anticancer 9-anilinoacridine derivatives, which are designed to avoid bio-oxidation and possessed long duration of drug action, is reviewed. Among these agents, 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) derivatives and their alkylcarbamates have been investigate...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867023369231

    authors: Su TL

    更新日期:2002-09-01 00:00:00

  • Non-antioxidant activities of vitamin E.

    abstract::Molecules in biological systems often can perform more than one function. In particular, many molecules have the ability to chemically scavenge free radicals and thus act in the test tube as antioxidant, but their main biological function is by acting as hormones, ligands for transcription factors, modulators of enzym...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867043365332

    authors: Zingg JM,Azzi A

    更新日期:2004-05-01 00:00:00

  • Drug repositioning for the treatment of hematologic disease: limits, challenges and future perspectives.

    abstract::Drug repositioning is a strategy to identify new uses for approved or investigational drugs that are used off-label outside the scope of the original medical indication. In this review we report the most relevant studies about drug repositioning in hematology, reporting the signalling pathways and molecular targets of...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/0929867327999200817102154

    authors: Allegra A,Imbesi C,Bitto A,Ettari R

    更新日期:2020-08-16 00:00:00

  • Proteomics and cardiovascular disease: an update.

    abstract::Proteomics has unraveled important questions in the biology of cardiovascular disease and holds even greater promise for the development of novel diagnostic and prognostic biomarkers. This approach may establish early detection strategies, and monitor responses to therapies. Technological advances (most notably blue n...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986708783769713

    authors: Balestrieri ML,Giovane A,Mancini FP,Napoli C

    更新日期:2008-01-01 00:00:00

  • Amyotrophic lateral sclerosis: from research to therapeutic attempts and therapeutic perspectives.

    abstract::Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons which brings to muscular atrophy, paralysis and death in 3-5 years from starting symptoms. In about 10% of cases ALS is familiar and in a relevant percent of these cases, mutations of the...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986711798347289

    authors: Contestabile A

    更新日期:2011-01-01 00:00:00

  • In vitro models for the study of non-alcoholic fatty liver disease.

    abstract::Non-alcoholic fatty liver disease is regarded as the hepatic manifestation of metabolic syndrome and is an important and common cause of chronic liver disease with a potential to develop end-stage liver disease. While important advances in the pathophysiology have been achieved using genetically modified and diet-indu...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986711794940842

    authors: Chavez-Tapia NC,Rosso N,Tiribelli C

    更新日期:2011-01-01 00:00:00

  • Diagnosis and therapeutic approaches to transthyretin amyloidosis.

    abstract::Hereditary amyloidogenic transthyretin (TTR) (ATTR) amyloidosis is an autosomal dominant form of fatal hereditary amyloidosis. Owing to progress in biochemical and molecular genetic analyses, this disease is now believed to occur worldwide. As of today, reports of about 120 different points of single or double mutatio...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986712800269317

    authors: Ando Y,Ueda M

    更新日期:2012-01-01 00:00:00

  • Rationally designed multitarget anti-HIV agents.

    abstract::Multitarget-directed ligands (MTDLs), an emerging and appealing drug discovery strategy, utilizing a single chemical entity to inhibit multitargets, was confirmed to be effective in reducing the likelihood of drug resistance, diminishing problems of dosing complexity, drug-drug interactions and toxicities, as well as ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867311320130011

    authors: Zhan P,Liu X

    更新日期:2013-01-01 00:00:00

  • Synthetic carriers: sequential oligopeptide carriers SOCn-I and SOCn-II as an innovative and multifunctional approach.

    abstract::Nowadays, the use of synthetic carriers as biochemical reagents and immunogens is entering a new phase. The multimeric nature of these constructs, the unambiguous composition and the ease, reliability and versatility of their production, make this type of carriers well-suited to various biotechnological and biochemica...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867054039062

    authors: Alexopoulos Ch,Sakarellos-Daitsiotis M,Sakarellos C

    更新日期:2005-01-01 00:00:00

  • Photobiostimulation on wound healing treatment by ClAlPc-nanoemulsion from a multiple-wavelength portable light source on a 3D-human stem cell dermal equivalent.

    abstract::This research evaluated the effect of multiple-wave lasertherapy on the healing process of surgical wounds based on in vitro models denominated stem-dermal equivalents. These human skin models were obtained from a co-culture of dermal cells and bone marrow mesenchymal stem cells. The experimental tests were carried ou...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/092986712803530502

    authors: Primo FL,de Paula LB,de Siqueira-Moura MP,Tedesco AC

    更新日期:2012-01-01 00:00:00

  • Fine-tuning of microRNAs in Type 2 Diabetes Mellitus.

    abstract::Type 2 diabetes mellitus is a metabolic disease widely spread across industrialized countries. Sedentary lifestyle and unhealthy alimentary habits lead to obesity, boosting both glucose and fatty acid in the bloodstream and eventually, insulin resistance, pancreas inflammation and faulty insulin production or secretio...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867325666171205163944

    authors: Rosado JA,Diez-Bello R,Salido GM,Jardin I

    更新日期:2019-01-01 00:00:00

  • New methods for medicinal chemistry--universal gene cloning and expression systems for production of marine bioactive metabolites.

    abstract::Natural products from symbiotic or commensal associations between marine invertebrate and microbial organisms show exceptional promise as pharmaceuticals in many therapeutic areas. An economic and sustainable global market supply due to difficulty of synthesis is cited as the main obstacle for exploitation of these ot...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986706776055643

    authors: Dunlap WC,Jaspars M,Hranueli D,Battershill CN,Perić-Concha N,Zucko J,Wright SH,Long PF

    更新日期:2006-01-01 00:00:00

  • Cannabinoid CB1 and CB2 receptor ligand specificity and the development of CB2-selective agonists.

    abstract::Cannabinoids in current use such as nabilone activate both CB1 and CB2 receptors. Selective CB2 activation may provide some of the therapeutic effects of cannabinoids, such as their immuno-modulatory properties, without the psychoactive effects of CB1 activation. Therefore, cannabinoid CB2 receptors represent an attra...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986708784567716

    authors: Ashton JC,Wright JL,McPartland JM,Tyndall JD

    更新日期:2008-01-01 00:00:00

  • DNA Damage Response as a Pharmacological Target for Cancer and Infectious Diseases.

    abstract:: ...

    journal_title:Current medicinal chemistry

    pub_type: 社论

    doi:10.2174/092986732608190516092613

    authors: Poplawski T

    更新日期:2019-01-01 00:00:00

  • Regulation of mast cell development by inflammatory factors.

    abstract::Mast cells are potent effectors playing a key role in IgE-associated hypersensitivity reactions, allergic disorders, inflammation and protective immune responses. Mast cell development in vivo occurs mainly in non-hematopoietic microenvironments and increased mast cell numbers can be seen in various inflammatory disea...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986707782793998

    authors: Hu ZQ,Zhao WH,Shimamura T

    更新日期:2007-01-01 00:00:00

  • Advances in the discovery of novel antibacterial agents during the year 2002.

    abstract::The development of bacterial resistance is a significant problem in the treatment of infection, and the importance of research directed toward the discovery of novel agents to treat infections cannot be underestimated. In the past, discovery programs have focused on modification of natural products or existing classes...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867043364658

    authors: Harris CR,Thorarensen A

    更新日期:2004-08-01 00:00:00

  • The discovery of the Factor Xa inhibitor otamixaban: from lead identification to clinical development.

    abstract::Factor Xa (fXa) is a critical serine protease situated at the confluence of the intrinsic and extrinsic pathways of the blood coagulation cascade. FXa catalyses the conversion of prothrombin to thrombin via the prothrombinase complex. Its singular role in thrombin generation, coupled with its potentiating effects on c...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986707782023659

    authors: Guertin KR,Choi YM

    更新日期:2007-01-01 00:00:00

  • Cholesterol Efflux and Reverse Cholesterol Transport: Experimental Approaches.

    abstract:BACKGROUND:Cholesterol efflux as a key event in reverse cholesterol transport (RCT) is considered now as both diagnostic tool and a promising target for the treatment of atherosclerosis. Radioactive in vitro cholesterol efflux assay (CEA) is the gold standard for determination of efflux at cellular level. Fluorescent t...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867323666160809093009

    authors: Litvinov DY,Savushkin EV,Garaeva EA,Dergunov AD

    更新日期:2016-01-01 00:00:00