Abstract:
:VEGF is an important signaling protein involved in both vasculogenesis and angiogenesis. As an essential receptor protein tyrosine kinase propagating cellular signal transduction processes, VEGFR-2 is a central target for drug discovery against tumor-associated angiogenesis. Since the autophosphorylation of VEGFR-2 represents a key step in this signal pathway that contributes to angiogenesis, the discovery of small molecule inhibitors that block this reaction has attracted great interest for novel drugs research and development. Advances in the understanding of catalytic cleft and the conformational changes of DFG motif have resulted in the development of small molecule inhibitors known as type I and type II. High-resolution crystal structures of various inhibitors in complex with the receptor offer an insight into the relationship among binding modes, inhibition mechanisms, activity, selectivity and resistance. To control selectivity, improve activity and introduce intellectual property novelty, the strategies for the further development are discussed through structural and conformational analysis in this review.
journal_name
Future Med Chemjournal_title
Future medicinal chemistryauthors
Huang L,Huang Z,Bai Z,Xie R,Sun L,Lin Kdoi
10.4155/fmc.12.121subject
Has Abstractpub_date
2012-09-01 00:00:00pages
1839-52issue
14eissn
1756-8919issn
1756-8927journal_volume
4pub_type
杂志文章,评审abstract::The design of a high-quality screening collection is of utmost importance for the early drug-discovery process and provides, in combination with high-quality assay systems, the foundation of future discoveries. Herein, we review recent trends and observations to successfully expand the access to bioactive chemical spa...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.11.15
更新日期:2011-04-01 00:00:00
abstract:AIM:The similarity in the biological function of the bioisosteric pair, carboxyl and sulfonamide functional groups, is studied using the quantitative tool, average electron density of the bioisosteric moiety in drug molecules and the qualitative tool, electrostatic potential. Results/methodology: Five different capping...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2017-0136
更新日期:2017-12-01 00:00:00
abstract:AIM:Triterpenes are natural compounds, whose wide biological activity predestines them for application as promising new chemotherapeutics. In this paper, we report the results of our investigations into the substitution of oleanolic acid with aromatic and nitroaromatic moieties acting as bioreducing agents. RESULTS:Th...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2017-0154
更新日期:2018-03-01 00:00:00
abstract::Since their initial isolation from the marine alga Delisea pulchra, bromofuranones have been investigated as potential inhibitors of quorum sensing (QS) in various bacterial strains. QS is an important mechanism by which bacteria co-ordinate their molecular response to the environment. QS is intrinsically linked to ba...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2020-0244
更新日期:2020-11-01 00:00:00
abstract:AIM:The pharmacotherapy of inflammatory bowel disease is difficult and currently available treatments bring mostly poor and unsatisfactory results. RESULTS:The purpose of this work was the synthesis of opiorphin, sialorphin, spinorphin and a series of their analogs and the in vitro characterization of their effect on ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2016-0156
更新日期:2016-12-01 00:00:00
abstract::This review aims to bring the reader up to date with the more recent ruthenium compounds that have been synthesized and tested for their cytotoxicity. The chemistry of these transition metal complexes will be introduced and the basic principles that govern their common behavior outlined. The recent history of establis...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.09.25
更新日期:2009-06-01 00:00:00
abstract::Trichomonas vaginalis and Entamoeba histolytica are clinically important protozoa that affect humans. T. vaginalis produces sexually transmitted infections and E. histolytica is the causative agent of amebic dysentery. Metronidazole, a compound first used to treat T. vaginalis in 1959, is still the main drug used worl...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.09.59
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND:Due to the complex nature of Alzheimer's disease, there is a renewed and growing search for multitarget drugs. RESULTS:Donepezil-ferulic acid hybrids (DFAHs) were prepared by the one-pot Ugi-4CR in low-to-moderate yields. DFAHs are potent antioxidant agents, showing oxygen radical absorbance capacity values...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.14.148
更新日期:2015-01-01 00:00:00
abstract::Cancer, still in the limelight due to its dreadful nature, shows overexpression of multiple signaling macromolecules leading to failure of many chemotherapeutic agents and acquired resistance to chemotherapy. These factors highlight the significance of shifting toward targeted therapy in cancer research. Recently, ERK...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2019-0339
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:The acquirement of resistance by microorganisms to the antimicrobial arsenal is a threat to public health. A recent WHO report estimated that 1.3 million HIV-negative people and 0.38 million HIV-positive people died from TB in 2009. Various forms of cancer account for a high percentage of deaths in both wome...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.12.57
更新日期:2012-06-01 00:00:00
abstract::Agents that interfere with tubulin function have a broad anti-tumor spectrum and they represent one of the most significant classes of anticancer agents. In the past few years, several small synthetic molecules that have an indole nucleus as a core structure have been identified as tubulin inhibitors. Among these, sev...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.12.141
更新日期:2012-10-01 00:00:00
abstract::The EGFR is one of the most popular targets for anticancer therapies and many drugs, such as erlotinib and gefitinib, have got enormous success in clinical treatments of cancer in past decade. However, the efficacy of these agents is often limited because of the quick emergence of drug resistance. Fundamental structur...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2016-0222
更新日期:2017-05-01 00:00:00
abstract::New Delhi Metallo β-lactamase-1 (NDM-1) is a member of the Metallo-β-lactamase family, capable of catalyzing the hydrolysis of all β-lactam antibiotics. The rapid dissemination of NDM producers, 'superbugs', has become a worldwide concern to health workers. Seventeen different variants of NDM have been reported so far...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2017-0143
更新日期:2018-01-01 00:00:00
abstract:AIM:This research paper is aimed at designing a novel insulin alternative for the treatment of diabetes. MATERIALS & METHODS:Six novel vanadyl(II) compounds, [(AMP-2)(VO+2)(AA n-1)]·NH4+1, were synthesized from an equimolar ratio of adenosine monophosphate, VOSO4 and amino acids (AA n ). RESULTS:The magnetic moments ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2018-0471
更新日期:2019-01-15 00:00:00
abstract::It is increasingly clear that academic high-throughput screening (HTS) and virtual HTS triage suffers from a lack of scientists trained in the art and science of early drug discovery chemistry. Many recent publications report the discovery of compounds by screening that are most likely artifacts or promiscuous bioacti...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.14.60
更新日期:2014-07-01 00:00:00
abstract:AIM:Tuberculosis is responsible for 9.6 million infections and 1.5 million deaths in 2015. The development of multidrug-resistant and extensively drug-resistant strains has impeded the development of effective antitubercular therapy. Results/methodology: The present manuscript describes the synthesis of a series of 4-a...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2017-0098
更新日期:2017-10-01 00:00:00
abstract:AIM:Due to the complex nature of Alzheimer's disease, there is a renewed search for pleiotropic agents. RESULTS:Purine+coumarin hybrids have been synthesized and tested for the potential treatment of Alzheimer's disease. Hybrids 6, 4a-b, 14c and 14e inhibit significantly soybean lipoxygenase, whereas derivatives 14b, ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.14.158
更新日期:2015-01-01 00:00:00
abstract::Aim: The explosion of data based technology has accelerated pattern mining. However, it is clear that quality and bias of data impacts all machine learning and modeling. Results & methodology: A technique is presented for using the distribution of first significant digits of medicinal chemistry features: logP, logS, a...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2019-0006
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:Due to the complex etiology of neurodegenerative diseases, there is growing interest in multitarget drugs. In this study we synthesized and evaluated a new series of compounds, with benzo[f]coumarin structure, as potential inhibitors of MAO-A, MAO-B, AChE and BuChE. RESULTS:In vitro studies show that most o...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.14.9
更新日期:2014-03-01 00:00:00
abstract::Acetyl-CoA carboxylase (ACC), a critical enzyme in the regulation of fatty acid synthesis and metabolism, has emerged as an attractive target for a plethora of emerging diseases, such as diabetes mellitus, nonalcoholic fatty liver disease, cancer, bacterial infections and so on. With decades of efforts in medicinal ch...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2019-0312
更新日期:2020-03-01 00:00:00
abstract::This review provides an overview of chemokines and their receptors, with an emphasis on general features and nomenclature along with a short summary of their properties and functions. It is intended as an introduction to the subject and a reference point for those wishing to learn key facts about chemokines and their ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.12.49
更新日期:2012-05-01 00:00:00
abstract::The emergence of antimicrobial resistance has created a need for the development of novel antibacterial therapies to treat infection. Natural products that exhibit antibacterial activity offer validated starting points for library generation, and the authors report here that small molecule mimics of tetramate-containi...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.15.97
更新日期:2015-01-01 00:00:00
abstract::Alzheimer's disease is a multifactorial syndrome, for which effective cures are urgently needed. Seeking for enhanced therapeutic efficacy, multitarget drugs have been increasingly sought after over the last decades. They offer the attractive prospect of tackling intricate network effects, but with the benefits of a s...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2016-0003
更新日期:2016-04-01 00:00:00
abstract::More research effort needs to be invested in antimicrobial drug development to address the increasing threat of multidrug-resistant organisms. The enzyme DHPS has been a validated drug target for over 70 years as the target for the highly successful sulfa drugs. The use of sulfa drugs has been compromised by the wides...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.13.97
更新日期:2013-07-01 00:00:00
abstract:AIM:Antibiotic resistance has become a major health problem. The σ(70):core interface of bacterial RNA polymerase is a promising drug target. Recently, the coiled-coil and lid-rudder-system of the β' subunit has been identified as an inhibition hot spot. Materials & methods & Results: By using surface plasmon resonance...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.14.105
更新日期:2014-09-01 00:00:00
abstract::Metal complexes have been the subject of numerous investigations in oncology but, despite the plethora of newly synthesized compounds, their precise mechanisms of action remain generally unknown or, for the best, incompletely determined. The continuous development of efficient and sensitive techniques in analytical ch...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2016-0153
更新日期:2016-12-01 00:00:00
abstract::MRI has been recognized as one of the most applied medical imaging techniques in clinical practice. However, the presence of background signal coming from water protons in surrounding tissues makes sometimes the visualization of local contrast agents difficult. To remedy this, fluorine has been introduced as a reliabl...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2018-0463
更新日期:2019-05-01 00:00:00
abstract:AIM:Confirm the use of Plectanthus spp. plants in traditional medicine, particularly as anti-inflammatory and anti-infective agents. MATERIALS & METHODS:Compounds previously isolated from Plectranthus spp. were studied for their anti-inflammatory activity using the SNAP assay and RAW 264.7 cells, by the quantification...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2018-0043
更新日期:2018-07-01 00:00:00
abstract::The protein kinase superfamily is one of the most important families of enzymes in molecular biology. Protein kinases typically catalyze the transfer of the γ-phosphate from ATP to a protein substrate (a highly ubiquitous cellular reaction), thereby controlling key areas of cell regulation. Deregulation of protein kin...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.09.50
更新日期:2009-10-01 00:00:00
abstract::Hepatitis B Virus (HBV) is one of the most prevalent viral infections of human worldwide. The therapies are limited in the clinical context because of negative side effects of interferons and the development of viral resistance to the nucleoside/nucleotide inhibitors. In this review, we summarize the recent advances i...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.15.19
更新日期:2015-01-01 00:00:00