Abstract:
:Introduction: DNA-dependent protein kinase (DNA-PK) plays a crucial role in the repair of DSBs via non-homologous end joining (NHEJ). Several DNA-PK inhibitors are being investigated for potential anticancer treatment in clinical trials. Area covered: This review aims to give an overview of patents published since 2010 by analyzing the patent space and structure features of scaffolds used in those patents. It also discusses the recent clinical developments and provides perspectives on future challenges and directions in this field. Expert opinion: As a key component of the DNA damage response (DDR) pathway, DNA-PK appears to be a viable drug target for anticancer therapy. The clinical investigation of a DNA-PK inhibitor employs both a monotherapy and a combination strategy. In the combination strategy, a DNA-PK inhibitor is typically combined with a DSB inducer, radiation, a chemotherapy agent, or a PARP inhibitor, etc. Patent analyses suggest that diverse structures comprising different scaffolds from mono-heteroaryl to bicyclic heteroaryl to tricyclic heteroaryl are capable to achieve good DNA-PK inhibitory activity and good DNA-PK selectivity over other closely related enzymes. Several DNA-PK inhibitors are currently being evaluated in clinics, with the hope to get approval in the near future.
journal_name
Expert Opin Ther Patjournal_title
Expert opinion on therapeutic patentsauthors
Hu S,Hui Z,Lirussi F,Garrido C,Ye XY,Xie Tdoi
10.1080/13543776.2021.1866540subject
Has Abstractpub_date
2020-12-21 00:00:00eissn
1354-3776issn
1744-7674pub_type
杂志文章abstract:INTRODUCTION:Caffeic acid (CA) is broadly distributed in several species of the plant kingdom and is widely consumed in human diet. CA and derivatives have been extensively studied in the past years, which unveiled a broad spectrum of biological activities and potential therapeutic applications. As a result, there has ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2014.959492
更新日期:2014-11-01 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:Monoacylglycerol lipase (MAGL) belongs to the endocannabinoid system and is responsible for the inactivation of endocannabinoid 2-arachidonoylglycerol. Importantly, it was found that MAGL degradation of lipids in cancer cells enhances the availability of free fatty acids for new cellular membrane formation...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1080/13543776.2021.1841166
更新日期:2020-11-01 00:00:00
abstract:INTRODUCTION:The NF-E2-related factor-2 (Nrf2) is a critical transcription factor that regulates the expression of many phase II and antioxidant genes to maintain the homeostasis. It has many biological functions and plays a central role in the cellular defensive machinery. The abnormal regulation of Nrf2 is closely as...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2017.1325464
更新日期:2017-07-01 00:00:00
abstract::Introduction: Phosphodiesterase 10 (PDE10) is one of at least 11 different PDE families, which are the enzymes that degrade adenosine 3',5'-cyclic monophosphate (cAMP) and/or guanosine 3',5'-cyclic monophosphate (cGMP) by hydrolyzing the phosphodiester bonds. Inhibition of PDE10A represents a molecular target in the t...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2020.1709444
更新日期:2020-02-01 00:00:00
abstract::A series of 10 closely related patent applications define Theravance's approach to the development of long-acting M(3) selective antagonists for the treatment of chronic obstructive pulmonary disease. The applications illustrate a modular approach to the design of such agents, comprising a muscarinic pharmacophore att...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.16.9.1321
更新日期:2006-09-01 00:00:00
abstract::Introduction: TIM3 and PD-1 are checkpoint inhibitors in cancer that coordinate the downregulation of the proliferation of antigen-specific lymphocytes. There is a great need to discover and develop new therapies focused on inhibiting the action of TIM3 and PD-1 and consequently improving the immune response in the va...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2019.1637422
更新日期:2019-08-01 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:c-Met kinase is the receptor for hepatocyte growth factor. Primarily expressed on epithelial and mesenchymal cells its normal function is associated with wound healing, liver regeneration and embryo development. However, dysregulation of c-Met through overexpression, gene amplification, mutation...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543770903514137
更新日期:2010-02-01 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:PROTACs represent a novel class of heterobifunctional molecules that simultaneously bind to a target protein and to an E3 ligase complex, resulting in the transfer of ubiquitin and initiating a process ultimately causing the proteasomal degradation of the target protein. This mechanism of action imbues PRO...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1080/13543776.2021.1840553
更新日期:2021-01-01 00:00:00
abstract:IMPORTANCE TO THE FIELD:Leukotrienes (LTs) are pivotal lipid mediators of inflammation and allergy and results from recent studies also suggest roles of LTs in cardiovascular diseases, cancer and osteoporosis. 5-Lipoxygenase (5-LO) catalyzes the first step in the biosynthesis of LTs from arachidonic acid, and based on ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543771003602012
更新日期:2010-03-01 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: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::Introduction: The greater interest in TAAR1-mediated potential for the treatment of different pathologies, especially those related to CNS disorders, has given a considerable boost to the search for developing TAAR1-selective small molecules.Areas covered: During the last decade, the medicinal chemistry efforts have a...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2020.1708900
更新日期:2020-02-01 00:00:00
abstract:INTRODUCTION:The bacterial topoisomerases DNA gyrase and topoisomerase IV are validated targets for development of novel antibacterial agents. Fluoroquinolones inhibit the catalytic GyrA and/or ParC(GrlA) subunit and have been commonly used, although these have toxicity liabilities that restrict their use. The ATPase G...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2019.1575362
更新日期:2019-03-01 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:INTRODUCTION:The benzopyran derivatives present a wide variety of biological activity and behaviour. At the same time the benzopyran derivatives support their use as therapeutic agents for multiple diseases. Their structural characteristics correlated to physicochemical properties seem to define the extent of the biolo...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2017.1338687
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:Sulfonamide compounds are significant class of synthetic bacteriostatic antibiotics still which used today for the therapy of bacterial infections and those caused by other microorganisms. They are also known as sulfa drugs and were the main source of therapy against bacterial infections before the introdu...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2018.1487400
更新日期:2018-07-01 00:00:00
abstract:INTRODUCTION:Chymase is primarily found in mast cells (MCs), fibroblasts, and vascular endothelial cells. MC chymase is released into the extracellular interstitium in response to inflammatory signals, tissue injury, and cellular stress. Among many functions, chymase is a major extravascular source for angiotensin II (...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2018.1531848
更新日期:2018-11-01 00:00:00
abstract:INTRODUCTION:The orexin system consists of two G-protein-coupled receptors, orexin 1 and orexin 2 and two endogenous ligands, orexin A and orexin B . It is evolutionarily highly conserved. It is involved in the promotion of wakefulness as well as in anxiety and addictive disorders. In addition, its activation via the O...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2017.1344221
更新日期:2017-10-01 00:00:00
abstract::The application is in the field of adult neurogenesis and its therapeutic potential. It aims to characterize the activity of apigenin and related compounds on adult neurogenesis in vivo and in vitro. Apigenin and related compounds are derivatives used in food products. They were administered intraperitoneally and oral...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543770902721279
更新日期:2009-04-01 00:00:00
abstract::The interaction between p53 and murine double minute 2 (MDM2) provides an attractive drug target in oncology. Small molecule inhibitors of this interaction have not only provided strong evidence for blocking the protein-protein interaction, but are also extremely useful as biological probes and ultimately as novel the...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.16.2.165
更新日期:2006-02-01 00:00:00
abstract::Novel 1-anilino-4-phenylphthalazine derivatives, compositions containing them, and their use as JAK1 inhibitors and for the treatment of cancer, inflammatory and autoimmune diseases are claimed. This represents a novel scaffold for JAK inhibitors and is highly distinct from the JAK1 inhibitors previously described, al...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2012.707647
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:The family of G-protein-coupled receptors (GPCRs) serves as the target for almost a third of currently marketed drugs and provides the predominant mechanism through which extracellular factors transmit signals to the cell. GPCRs have been proved to be good therapeutic targets for metabolic disorders. In rece...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543770802665717
更新日期:2009-02-01 00:00:00
abstract:INTRODUCTION:Indazoles are heterocyclic moieties rarely found in nature. They are nitrogen containing chemical compounds composed of a pyrazole ring condensed with a benzene ring. Various indazole derivatives have been described with a wide variety of biological activities. This has aroused great interest in the develo...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2018.1472240
更新日期:2018-06-01 00:00:00
abstract:INTRODUCTION:Quantitative Structure-Activity Relationship (QSAR) models are becoming one of the most interesting fields for developing therapeutics and therapeutics related patents. At present, QSAR methodologies comprise a series of possibilities, including joining forces with machine learning methods and increasing e...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2018.1475560
更新日期:2018-06-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Nonsteroidal estrogens have been known since the 1930s. However, the relatively recent (1996) discovery of estrogen receptor subtype beta (ERbeta) suggested a possible paradigm shift away from SERM-like selectivity. Selective ERbeta agonism would potentially allow expansion of estrogenic targeti...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543771003657164
更新日期:2010-04-01 00:00:00
abstract::The patent claims peptidic/nonpeptidic inhibitors of the ghrelin receptor, the growth hormone secretagogue receptor (GHSR) 1A. Among these compounds, it was disclosed that the addition in some compounds of a GlyMetAla tripeptide at the N-terminus of the ghrelin peptide agonists converts them into ghrelin receptor anta...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2012.684946
更新日期:2012-06-01 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