Abstract：
IMPORTANCE OF THE FIELD:Following FDA approval of vorinostat in 2006, several novel HDAC inhibitors (HDACis) have entered clinical trials, and there are numerous published patent applications claiming novel HDACis which were optimized as potential drug candidates, designed for regional or systemic release, and created as dual or multifunctional inhibitors. Given the breadth and depth of recent reporting of novel HDACis, there has emerged a need to review the field from a chemist's perspective in one compact article. AREAS COVERED IN THIS REVIEW:This review provides a summary of published patent applications claiming novel HDACis from 2007 until mid-2009, covering mainly classes I, II and IV anticancer HDACis including those that have recently advanced to the clinic. WHAT THE READER WILL GAIN:Readers will rapidly gain an overview of the majority of HDACi scaffolds with representative structure-activity relationships; they will learn how these new compounds were created, how their drug like properties were improved and which companies are the main players in the field. TAKE HOME MESSAGE:Although competition in this field is intense, the future application of HDACis to treat human disease either as single agents or in combination with existing drugs holds real promise.
journal_name
Expert Opin Ther Patjournal_title
Expert opinion on therapeutic patentsauthors
Wang H,Dymock BWdoi
10.1517/13543770903393789subject
Has Abstractpub_date
2009-12-01 00:00:00pages
1727-57issue
12eissn
1354-3776issn
1744-7674journal_volume
19pub_type
杂志文章,评审abstract：INTRODUCTION:The use of inhibitors of HIV-1 integrase for treating HIV-1 infection has proven to be very beneficial. Raltegravir, a strand transfer inhibitor, has been approved for use both as a first-line therapy and in treatment-experienced patients. A second compound in this class, elvitegravir, is in Phase III clin...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2011.586631
更新日期：2011-08-01 00:00:00
abstract：:In the upcoming case of Teva Pharmaceuticals v. Sandoz, the U.S. Supreme Court will address how much deference the appellate court should afford to a trial court's claim construction ruling. The effect of this decision will be far-reaching, as how claims are construed can determine whether a patent is infringed or not...
journal_title：Expert opinion on therapeutic patents
pub_type： 社论
doi：10.1517/13543776.2014.977866
更新日期：2015-01-01 00:00:00
abstract：:Diabetes mellitus is a major threat to global public health that requires long-term medical attention. In view of the potentially devastating effects of diabetes on ocular health, it highlights the urgent need of therapeutic drugs for the prevention and treatment of the diabetic complications. The patent described in ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1517/13543776.2016.1163339
更新日期：2016-06-01 00:00:00
abstract：INTRODUCTION:Xanthine oxidase (XO) is a molybdoflavoprotein that catalyzes the oxidative hydroxylation of purines to produce uric acid and reactive oxygen species. These reaction products can cause severe disease conditions like hyperuricemia which makes XO enzyme, an important therapeutic target in diseases like gout....
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1080/13543776.2020.1811233
更新日期：2020-10-01 00:00:00
abstract：IMPORTANCE OF THE FIELD:Small molecule glucokinase activators (GKAs) continue to represent a potential strategy to treat type 2 diabetes (T2D). Glucokinase (GK) primarily exerts its effect through modulatory actions in pancreatic β-cells and hepatocytes. It couples insulin secretion in the pancreas with plasma glucose ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2011.542413
更新日期：2011-01-01 00:00:00
abstract：:In recent years, the involvement of the Hedgehog (Hh) signaling pathway in various human diseases and dysfunctions has been clearly demonstrated. Smoothened (Smo), one of the upstream signal transducers, has been the most druggable target of the Hh pathway. However, the emergence of resistance to Smo inhibitors and th...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1517/13543776.2016.1132309
更新日期：2016-01-01 00:00:00
abstract：BACKGROUND:Not only hypercholesterolemia, but also low levels of high-density lipoprotein cholesterol is a critical risk factor for atherosclerosis-related disease. Therefore, there has been great interest in identifying effective and selective cholesteryl ester transfer protein (CETP) inhibitors that can raise high-de...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543770903198451
更新日期：2009-09-01 00:00:00
abstract：INTRODUCTION:Inhibitors of programmed cell death 1 (PD-1) and its ligands are producing a paradigm shift in cancer treatment. The promising clinical outcomes and a multi-billion dollar market have prompted active research and development and resulted in relentless patent protection. However, the global patent landscape...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2017.1378349
更新日期：2018-01-01 00:00:00
abstract：INTRODUCTION:2,5-Diketopiperazines (DKPs) are cyclic dipeptides from two amino acids with or without further structural modifications in DKP nucleus. These DKPs demonstrated attractive bioactive diversity and potential in drug discovery. AREAS COVERED:This review summarized those bioactive DKPs in patents, and provide...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2013.828036
更新日期：2013-11-01 00:00:00
abstract：BACKGROUND:Many polycationic cell penetrating peptides (CPPs), alternatively named protein transduction domains, have been used for the efficient intracellular delivery of biologically active agents. Patent WO2008/082885 relates to the properties and proposed biomedical applications of a CPP and putative-related sequen...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/17530050902824829
更新日期：2009-09-01 00:00:00
abstract：INTRODUCTION:The cyclic nucleotides cAMP and cGMP are ubiquitous intracellular second messengers regulating a large variety of biological processes. The intracellular concentration of these biologically relevant molecules is modulated by the activity of phosphodiesterases (PDEs), a class of enzymes that is grouped in 1...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2016.1203902
更新日期：2016-08-01 00:00:00
abstract：INTRODUCTION:TANK-binding kinase 1 (TBK1) is a noncanonical IκB kinase family member that regulates the innate immune response. Misregulation of TBK1 activity can promote inflammatory disorders and oncogenesis; therefore, TBK1 inhibitors are considered a promising therapy for inflammation and cancer. AREAS COVERED:In ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2015.1081168
更新日期：2015-01-01 00:00:00
abstract：BACKGROUND:Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. Hyperglycemia, or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543770903153878
更新日期：2009-10-01 00:00:00
abstract：IMPORTANCE OF THE FIELD:Aberrant activation of signal transducer and activator of transcription (Stat) 3, a member of the STAT family of proteins, is prevalent in numerous human cancers and is now widely recognized as a critical molecular abnormality and a master regulator of tumor processes. Thus, the identification o...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2011.539205
更新日期：2011-01-01 00:00:00
abstract：:Introduction: Pharmacotherapy is limited by the inefficient drug targeting of non-healthy cells/tissues. In this pharmacological landscape, liposomes are contributing to the impulse given by Nanotechnology to optimize drug therapy. Areas covered: The analysis of the state-of-the-art in liposomal formulations for drug ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2019.1679767
更新日期：2019-11-01 00:00:00
abstract：:Muscular dystrophies (MD) are commonly characterized by progressive loss of muscle mass and function. It is hypothesized that therapeutic blockade of the TGF-β ligand myostatin, a negative regulator of muscle mass, will stimulate muscle growth and restore muscle function. Although many anti-myostatin targets are curre...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1517/13543776.2015.1007954
更新日期：2015-05-01 00:00:00
abstract：INTRODUCTION:Tropomyosin receptor kinases (TrkA/B/C) play crucial roles in the development and maintenance of the nervous system, and aberrant expression of Trk has been implicated in neurological disorders as well as neural and non-neural neoplasms. Patent activity encompassing Trk inhibitors has grown substantially o...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2017.1297796
更新日期：2017-06-01 00:00:00
abstract：INTRODUCTION:Today, over 20 million people suffer from Alzheimer's disease (AD) worldwide. AD has become a critical issue to human health, especially in aging societies, and therefore it is a research hotspot in the global scientific community. The technology flow method differs from traditional reviews generating an i...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2018.1439475
更新日期：2018-04-01 00:00:00
abstract：INTRODUCTION:Biotech patents are facing increasingly stern challenges. The patent statue holds that a multi-step method patent is not directly infringed unless all steps are carried out and attributed to a single entity. When separate steps are performed jointly by two or more parties, those parties are liable for divi...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1080/13543776.2017.1301930
更新日期：2017-04-01 00:00:00
abstract：IMPORTANCE OF THE FIELD:T-type calcium channels are transmembrane proteins that regulate calcium entry in the cell in a voltage-dependent manner. Intracellular calcium levels are the key to many physiological processes, ranging from neuron firing to cardiac pacemaking. Inhibition of T-type calcium channels is heralded ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2011.536532
更新日期：2011-01-01 00:00:00
abstract：INTRODUCTION:Aldose reductase (ALR2) is both the key enzyme of the polyol pathway, whose activation under hyperglycemic conditions leads to the development of chronic diabetic complications, and the crucial promoter of inflammatory and cytotoxic conditions, even under a normoglycemic status. Accordingly, it represents ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2019.1582646
更新日期：2019-03-01 00:00:00
abstract：INTRODUCTION:The N-acylhydrazone (NAH) moiety has been characterized as a privileged structure, capable of providing ligands points for more than one type of bioreceptor. Modifications of the subunits bonded to its acyl and imine functions resulted in several derivatives, which modulate a great diversity of molecular t...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2014.959491
更新日期：2014-11-01 00:00:00
abstract：:Increasing pharmacological studies have demonstrated that organic cation transporter 3 (OCT3) plays an important role in controlling the extracellular concentrations of released monoamine neurotransmitter, suggesting that OCT3 might be a promising target in the treatment of depression. As a consequence, compounds show...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1080/13543776.2016.1180364
更新日期：2016-08-01 00:00:00
abstract：INTRODUCTION:Due to the role of bradykinin B1 receptor (B1R) in pain and inflammation, B1R antagonists have been suggested as promising drug candidates in chronic pain states. The first disclosed B1R antagonists were peptidomimetics, however, during the last few years, novel chemotypes with improved pharmacodynamic and...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2012.730521
更新日期：2012-12-01 00:00:00
abstract：:Introduction: Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase. Upon collagen binding, DDR1 undergoes tyrosine autophosphorylation, which consequently triggers downstream genetic and cellular pathways and plays critical roles in the regulation of cellular morphogenesis, differentiati...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2020.1732925
更新日期：2020-05-01 00:00:00
abstract：INTRODUCTION:Bitopic M ligands, that is, ligands that interact both with the ortho- and allosteric binding sites of the M receptor subtypes, hold great potential as novel selective for muscarinic acetylcholine (M) ligands for several therapeutic applications. Areas covered: The patent application describes a set of com...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1080/13543776.2017.1272577
更新日期：2017-02-01 00:00:00
abstract：INTRODUCTION:Transglutaminases (TGases) are a class of enzymes that play multifunctional roles. Their protein-crosslinking activity has been linked to fibrosis and Huntington's disease, their glutamine deamidation activity has been related to celiac disease and their GTP-binding activity has been implicated in cancer. ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2016.1115836
更新日期：2016-01-01 00:00:00
abstract：INTRODUCTION:Angiogenesis is an important component of certain normal physiological processes, but aberrant angiogenesis contributes to some pathological disorders and in particular to tumor growth. Activation of vascular endothelial growth factor receptor-2 (VEGFR-2) by vascular endothelial growth factor (VEGF) is a c...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2017.1344215
更新日期：2017-09-01 00:00:00
abstract：INTRODUCTION:Antimicrobial peptides (AMPs) represent the large group of endogenous compounds widely distributed in nature. Due to their broad spectrum of antibiotic activity, as well as anti-inflammatory and immunomodulatory properties, AMPs became a model for the discovery of novel antimicrobial drugs that could answe...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2016.1176149
更新日期：2016-06-01 00:00:00
abstract：INTRODUCTION:Therapeutic antibodies have grown to become an important product class within the biopharmaceutical market. A prerequisite to their commercialization is adequate patent protection. Disclosure requirements and the types of claims available in different jurisdictions can impact the scope of protection availa...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2017.1296950
更新日期：2017-08-01 00:00:00
