Abstract:
:Histone Deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval by the FDA of four HDAC inhibitors, vorinostat, romidepsin, belinostat and panobinostat, used for the treatment of cutaneous/peripheral T-cell lymphoma and multiple myeloma. Many more HDAC inhibitors are at different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. Also, clinical trials of several HDAC inhibitors for use as anti-cancer drugs (alone or in combination with other anti-cancer therapeutics) are ongoing. In the intensifying efforts to discover new, hopefully, more therapeutically efficacious HDAC inhibitors, molecular modelingbased rational drug design has played an important role. In this review, we summarize four major structural classes of HDAC inhibitors (hydroxamic acid derivatives, aminobenzamide, cyclic peptide and short-chain fatty acids) that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Cappellacci L,Perinelli DR,Maggi F,Grifantini M,Petrelli Rdoi
10.2174/0929867325666181016163110subject
Has Abstractpub_date
2020-01-01 00:00:00pages
2449-2493issue
15eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-93733journal_volume
27pub_type
杂志文章,评审abstract::Currently available therapeutic options for non-insulin-dependent diabetes mellitus, such as dietary modification, oral hypoglycemics, and insulin, have limitations of their own. Many natural products and herbal medicines have been recommended for the treatment of diabetes. The present paper reviews medicinal plants t...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706776360860
更新日期:2006-01-01 00:00:00
abstract::Xanthones (dibenzo-γ-pyrones) constitutes an important class of oxygenated heterocycles and occur as secondary metabolites in plants and microorganisms. They are known for various biological activities such as antioxidant, monoamine oxidase inhibitor, antihypertensive, hepatoprotective, antithrombotic, antifungal and ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/09298673113209990144
更新日期:2013-01-01 00:00:00
abstract::The existence of functional NT/dopamine interactions in the central nervous system has been extensively documented. Among others, a possible molecular mechanism underlying the NT-induced modulation of dopamine release is a direct antagonistic NTS(1)/D(2) receptor interaction. More recently, neurochemical experiments a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712803414268
更新日期:2012-01-01 00:00:00
abstract::Although it has become acceptable that neuroretinal cells are also affected in diabetes, vascular lesions continue to be considered as the hallmarks of diabetic retinopathy. Animal models are essential for the understanding and treatment of human diabetic retinopathy, and the mouse is intensively used as a model becau...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/09298673113209990028
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:The possibilities of treatment for oncological diseases are growing enormously in the last decades. Unfortunately, these developments have led to the onset of resistances with regards to the new treatments. This is particularly true if we face with the therapeutic field of Tyrosine Kinase Inhibitors (TKIs). ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180607092451
更新日期:2019-01-01 00:00:00
abstract::Endothelial cells (ECs) play a pivotal role in physiological and altered tissue neovascularization. They face multiple morphological, biochemical and functional changes during the different phases of angiogenesis, under the regulation of a great number of proangiogenic and antiangiogenic signals, including soluble and...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709789878210
更新日期:2009-01-01 00:00:00
abstract::Two-component signal transduction systems and their expanded variants known as phosphorelays are integral elements of the virulence and antimicrobial resistance responses of a wide range of pathogenic bacteria and fungi and also regulate essential functions. As a consequence, two-component systems and phosphorelays ar...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867043455765
更新日期:2004-03-01 00:00:00
abstract::TB drug development pipeline represents varied structural classes of molecules. Oxazolidinones represent synthetic anti-bacterial agents with unique mechanism of action having wide spectrum of activity, oral bioavailability and well established SAR. They act by inhibiting translation at the initiation phase of protein...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666151106125759
更新日期:2015-01-01 00:00:00
abstract::The importance of organometallics can be noticed by their presence in all life organisms. The most known natural organometallic molecule is vitamin B12, a porphyrin containing a cobalt atom, useful for several enzymatic transformations. Based on the remarkable properties of this class of compounds, a new area of medic...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710791859306
更新日期:2010-01-01 00:00:00
abstract::Kinetoplastid and apicomplexan parasites comprise a group of protozoans responsible for human diseases, with a serious impact on human health and the socioeconomic growth of developing countries. Chemotherapy is the main option to control these pathogenic organisms and nucleotide metabolism is considered a promising a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180926154329
更新日期:2019-01-01 00:00:00
abstract::Anticancer drugs are often nonselective antiproliferative agents (cytotoxins) that preferentially kill dividing cells by attacking their DNA at some level. The lack of selectivity results in significant toxicity to noncancerous proliferating cells. These toxicities along with drug resistance exhibited by the solid tum...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708785132997
更新日期:2008-01-01 00:00:00
abstract::Symmetry plays a crucial role in a variety of biological processes. For instance, many protein receptors, upon activation, dimerize to its active form and subsequently produce its biological action. Hence, there is a renewal of curiosity for the synthesis of dimeric molecules (or bivalent ligands) capable, not only to...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706775197908
更新日期:2006-01-01 00:00:00
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
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family that plays a key role in the inflammatory process. It has been broadly studied in the aspect of its role in obesity and diabetes related diseases. MCP-1 causes the infiltration of macrophages into obese adipose tissue via bindi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170303162935
更新日期:2017-01-01 00:00:00
abstract::It is well accepted that inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is one of high risk factors for colorectal cancer (CRC). This supports the notion that inflammation plays a key role in cancer development. Epidemiologic studies have shown that vitamin D (Vit D) deficiency is ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867323666161202153028
更新日期:2017-01-01 00:00:00
abstract::Benzamide riboside (BR) after anabolism to an analogue of NAD, was shown to inhibit the activity of NAD-dependent enzymes such as inosine 5'-monophosphate dehydrogenase (IMPDH), the rate limiting enzyme in de novo guanylate biosynthesis, and malate dehydrogenase which is involved in the citric cycle and respiratory ch...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867024606849
更新日期:2002-04-01 00:00:00
abstract::Magnetic resonance imaging (MRI) contrast agents are utilized adjunctively to enhance the contrast between normal and abnormal structures on MRI scans. Along with the rapid evolution of the field has come a new appreciation for the medicinal chemistry of this unique class of metallopharmaceuticals. The efficacy of MRI...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867053507379
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Diabetic nephropathy (DN) is an important diabetic microvascular complication, and it is becoming the leading cause of end-stage renal disease worldwide. Unfortunately, there are no effective therapies to treat established DN. Therefore, new therapeutic targets are urgently required. Accumulating studies ind...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170509121003
更新日期:2017-01-01 00:00:00
abstract::Adenosine is an important autocoid, exerting its physiological effects on the human body by activation of four different G-protein-coupled-receptors (GPCRs) classified as A(1), A(2A), A(2B), and A(3). These receptors are coupled to secondary messenger systems including adenylate cyclase, inositol phosphate metabolism,...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710792927831
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Neuronal α4β2 nAChRs are receptors involved in the role of neurotransmitters regulation and release, and this ionic channel participates in biological process of memory, learning and attention. This work aims to review the structure and functioning of the α4β2 nAChR emphasizing its role in the treatment of a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180410105135
更新日期:2019-01-01 00:00:00
abstract::ATP-sensitive K(+) channels (K(ATP)channels) regulate insulin secretion by coupling intracellular metabolic changes to excitability of the plasma membrane in pancreatic beta-cells. The channels are closed when extracellular glucose levels are elevated due to enhanced feature. By contrast, cardiac-type K(ATP) channels,...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033368475
更新日期:2003-02-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are a large family of calcium-dependent zinc- containing endopeptidases, which are responsible for the tissue remodeling and degradation of the extracellular matrix (ECM), including collagens, elastins, gelatin, matrix glycoproteins, and proteoglycan. The inappropriate expression of th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711795471329
更新日期:2011-01-01 00:00:00
abstract::Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hybrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can result in compounds pres...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707781058805
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:N-acetyl-cysteine (NAC) has shown widespread utility in different psychiatric disorders, including a beneficial role in schizophrenic patients. Although the replenishment of glutathione and the antioxidant activity of NAC have been suggested as the mechanisms that improve such a wide range of disorders, none...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666191015091346
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Inflammation is one of the most misunderstood aspects of human health. People have been encouraged to eat foods that have a high antioxidant capacity, and in vitro tests for total antioxidant capacity emerged. They were based on measuring the destruction of oxidized test compounds in direct reactions with th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190517113533
更新日期:2020-01-01 00:00:00
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
更新日期:2002-09-01 00:00:00
abstract::The main challenge of cancer treatment is multidrug resistance during chemotherapy. Cancer cell can evade cell death during every round of orthodox chemotherapy drugs, consequently being resistant after several rounds of standard drug treatment. One of the regimens to address this multidrug resistance problem is by dr...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170920161922
更新日期:2018-01-01 00:00:00
abstract::Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme of cholesterol synthesis. In recent years, statins have become the major choice of treatment for hypercholesterolemia. Emerging evidence from both animal and human studies indicates that mechanisms i...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033457205
更新日期:2003-08-01 00:00:00
abstract::The signal transducers and activators of transcription (STATs) include a class of cytoplasmic signaling proteins whose role in the regulation of cell growth and survival is mediated by phosphorylation of a critical tyrosine residue within the STAT protein. This occurs in response to cytokines and growth factors modula...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711795843218
更新日期:2011-01-01 00:00:00
abstract::The concept of click chemistry represented by the formation of the 1,2,3-triazole core has found wide application in drug discovery, particularly in the early discovery phases and the lead optimization process. 1,2,3-Triazoles ha ve attracted considerable attention in recent years because of their wide range of biolog...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666150227150127
更新日期:2015-01-01 00:00:00