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 the identification of Smo-independent activation of the Hh pathway led to the need to find new chemical entities able to interfere with downstream components, such as Gli. For this purpose, two different computational approaches have been applied to a small-sized library of natural compounds. As a result, an isoflavone derivative that showed ability to inhibit both Smo and Gli1 has been identified; namely, Glabrescione B. A new synthetic approach has been planned for this compound and its derivatives. Biological evaluation demonstrated the mechanism of action and showed a promising preclinical profile.
journal_name
Expert Opin Ther Patjournal_title
Expert opinion on therapeutic patentsauthors
Manetti F,Petricci Edoi
10.1517/13543776.2016.1132309subject
Has Abstractpub_date
2016-01-01 00:00:00pages
529-35issue
4eissn
1354-3776issn
1744-7674journal_volume
26pub_type
杂志文章abstract::A small series of aryl(1-arylamino)ethyl,1,5-naphthyridine derivatives that selectively inhibit PI3Kδ was prepared. The compounds are claimed to be useful in the treatment of cancer, inflammatory and autoimmune diseases. The compounds represent further variations around a structural motif explored in a number of previ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2011.622749
更新日期:2011-11-01 00:00:00
abstract::In addition to its central role in haemostasis and wound healing, thrombin activates platelets and smooth muscle cells by proteolytic activation of cell surface protease-activated receptor-1 (PAR-1), which is also known as the thrombin receptor. Thrombin is the most potent activator of human platelets and, as such, a ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.16.4.493
更新日期:2006-04-01 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: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: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::Since the discovery of MK-0518 (raltegravir, the first FDA-approved integrase inhibitor) in October 2007, Merck Co. researchers have continued to patent original new heterocycles related to raltegravir as powerful strand transfer inhibitors. Among the most recent patented works hexahydrodiazocino-naphthyridinetriones ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543770802603577
更新日期:2009-01-01 00:00:00
abstract::Neurostatin, a natural glycosphingolipid inhibitor of astroblast and astrocytoma division, present in mammalian brain, is the modified ganglioside O-acetylated GD1b. It is cytostatic for rat astroblasts, C6 glioma cells and various human astrocytoma lines grades III and IV, with median inhibitory dose values ranging 1...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.14.4.487
更新日期:2004-04-01 00:00:00
abstract:INTRODUCTION:The activation of leukocytes and the subsequent immune cascade play an essential role in sterile and infectious inflammation. Dysregulation of these immune responses or excess leukocyte activation can induce tissue damage, organ dysfunction and mortality. Formyl peptide receptors (FPRs) are functionally di...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1080/13543776.2016.1216546
更新日期:2016-10-01 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::Small-molecule ligands, amenable to positron emission tomography (PET) imaging of different types of neurodegenerative disease-associated amyloid deposits in the CNS of living patients, hold considerable promise for diagnostic purposes, as well as for monitoring disease progression and the effectiveness of treatments....
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2014.871526
更新日期:2014-03-01 00:00:00
abstract:INTRODUCTION:Benzoxaborole is a versatile boron-heterocyclic scaffold which has found in the last 10 years a broad spectrum of applications in medicinal chemistry, due to its physicochemical and drug-like properties. Use of benzoxaborole moiety in the design of compounds led to the discovery of new classes of anti-bact...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2018.1473379
更新日期:2018-06-01 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: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: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: 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: 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 201...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1080/13543776.2021.1866540
更新日期:2020-12-21 00:00:00
abstract:BACKGROUND:Severe acute respiratory syndrome (SARS) coronavirus emerged fleetingly in the winter of 2002 and again in the winter of 2003, resulting in the infection of ~8,000 people and the death of ~800. The identification of the putative natural reservoir suggests that a re-emergence is possible. The functions of man...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543770802609384
更新日期:2009-03-01 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:BACKGROUND:The application (US20100233143) is in the field of embryonic stems cells (ESCs) and the generation of ESCs from parthenogenetically activated human oocytes. OBJECTIVE:It aims at determining optimal conditions for parthenogenetically activating human oocytes. METHODS:Oocytes isolated from female donors were...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.581230
更新日期:2011-08-01 00:00:00
abstract:INTRODUCTION:Autophagy is a lysosome-dependent degradation pathway that maintains cellular homeostasis in response to a variety of cellular stresses. Accumulating reports based on animal models have indicated the importance of this catabolic program in many human pathophysiological conditions, including diabetes, neuro...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2016.1217996
更新日期:2016-11-01 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::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:The appetite stimulating effects of melanin-concentrating hormone (MCH) continues to be of high interest, and there is substantial support to investigate the use of MCH 1-receptor antagonists for the treatment of obesity. Other areas of potential use for MCH 1-receptor antagonists include depression and an...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.575063
更新日期:2011-06-01 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:Hypertension represents a substantial cardiovascular risk factor. Among anti-hypertensive drugs, diuretics play an important role. Nevertheless, they present adverse effects such as hypokalemia or hyperkalemia. In this panorama, inhibitors of the renal outer medullary potassium (ROMK) channels are emerging...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2015.1050792
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Piperine is a simple and pungent alkaloid found in the seeds of black pepper (Piper nigrum). Following its isolation and full characterization, the biological properties of piperine have been extensively studied, and piperine-like derivatives have shown an interesting range of pharmacological activities. I...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2016.1118057
更新日期:2016-01-01 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:INTRODUCTION:With the introduction of mucoadhesion in 1980, pharmaceutical researchers have gained interest in mucoadhesive compositions. This interest has led to the development of mucoadhesive drug delivery systems aiming (I) to target a specific tissue, (II) to overcome barriers to absorption as well as (III) to con...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2016.1145209
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:Since the 1970s, the treatment options for asthma and chronic obstructive pulmonary disease have increasingly relied upon the use of inhaled drug formulations, generally from handheld inhaler devices. The introduction of combinations of a corticosteroid with a long-acting β2 agonist has dramatically transf...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2015.1064394
更新日期:2015-01-01 00:00:00