Abstract:
:Cancer and arthritis present an enormous challenge to society. They share pathogenic pathways that involve extracellular matrix degradation, tissue invasion, and inflammation. Most cancer and arthritis treatments affect normal cell function to cause significant adverse effects in patients. Specific pathways that promote cancer and arthritis progression must be elucidated to design more targeted and effective therapeutics. The Src kinase and podoplanin (PDPN) receptor are upregulated in cancer cells, fibroblasts, synoviocytes, and immune cells that increase tissue invasion and inflammation to promote both cancer and arthritis. In this review, we discuss how Src and PDPN forge a path to tissue destruction, and how they can serve as targets for therapeutics to combat cancer and arthritis.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Krishnan H,Miller WT,Blanco FJ,Goldberg GSdoi
10.1016/j.drudis.2018.07.009subject
Has Abstractpub_date
2019-01-01 00:00:00pages
241-249issue
1eissn
1359-6446issn
1878-5832pii
S1359-6446(18)30189-2journal_volume
24pub_type
杂志文章,评审abstract::Natural products (NPs) have been at the origin of several established drugs against tuberculosis (TB). Although the current clinical TB pipeline does not feature any candidates derived from new NP scaffolds, numerous novel NPs or NP analogs have been discovered in the recent past with promising activity against Mycoba...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.11.015
更新日期:2017-03-01 00:00:00
abstract::Cancer is the second highest cause of death worldwide. Several therapeutic approaches, such as conventional chemotherapy, antibodies and small molecule inhibitors and nanotherapeutics have been employed in battling cancer. Amongst them, nanotheranostics is an example of successful personalized medicine bearing dual ro...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.08.009
更新日期:2019-02-01 00:00:00
abstract::Micro RNAs (miRNAs) are a class of naturally occurring ∼ 22 nt long non-coding small RNA molecules that regulate the expression of a wide range of genes involved in development, growth, proliferation and apoptosis. miRNAs are evolutionarily conserved from plants to animals, and they regulate and fine-tune a diverse ar...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2010.07.003
更新日期:2010-09-01 00:00:00
abstract::Clinically useful drugs target a relatively small number of proteins that lie within a clearly defined and chemically accessible space. However, many high value biological targets lie outside this chemical space, and an ability to access such 'intractable' targets not amenable to traditional small molecule interventio...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.10.008
更新日期:2013-03-01 00:00:00
abstract::Chemokines are proinflammatory mediators that primarily control leukocyte migration into selected tissues and upregulation of adhesion receptors. They also have a role in pathological conditions that require neovascularization and are implicated in the suppression of viral replication. By interaction with their respec...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(98)01280-x
更新日期:1999-02-01 00:00:00
abstract::The recent increase in pharmaceutical companies' efforts toward the treatment of obesity reflects recognition of the related health risks, the growth of knowledge about mechanisms that control energy balance, and the potential market for new compounds. The current patent literature gives a picture of the targets that ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03244-1
更新日期:2004-10-15 00:00:00
abstract::It is widely accepted that placental ischemia is central in the evolution of hypertension in pregnancy. Many studies and reviews have targeted placental ischemia to explain mechanisms for initiating pregnancy hypertension. The placenta is rich in blood vessels, which are the basis for developing placental ischemia. Ho...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.10.021
更新日期:2018-02-01 00:00:00
abstract::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01674-3
更新日期:2001-03-01 00:00:00
abstract::SNPs can alter protein function and phenotype, leading to altered pharmacogenomic drug profiles. The exponential number of SNPs makes it impossible to perform wet laboratory experiments to determine the biological significance of each one. However, bioinformatics tools can be used to screen for potentially deleterious...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2011.07.005
更新日期:2011-09-01 00:00:00
abstract::Mice have been excellent surrogates for studying neutrophil biology and, furthermore, murine models of human disease have provided fundamental insights into the roles of human neutrophils in innate immunity. The emergence of novel humanized mice and high-diversity mouse populations offers the research community innova...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.03.018
更新日期:2020-06-01 00:00:00
abstract::Allosteric modulators have the potential to fine-tune protein functional activity. Therefore, the targeting of allosteric sites, as a strategy in drug design, is gaining increasing attention. Currently, it is not trivial to find and characterize new allosteric sites by experimental approaches. Alternatively, computati...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.07.012
更新日期:2014-10-01 00:00:00
abstract::Healthcare systems are faced with the challenge of providing innovative treatments, while shouldering high drug costs that pharmaceutical companies justify by the high costs of R&D. An emergent technology that could transform R&D efficiency is organ-on-a-chip. The technology bridges the gap between preclinical testing...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.06.003
更新日期:2019-09-01 00:00:00
abstract::'The climate is perfect for a proactive search for partners between industry and academia.' ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01543-9
更新日期:2000-09-01 00:00:00
abstract::Implementation of pragmatic design elements in drug development could bridge the evidence gap that currently exists between the knowledge we have regarding the efficacy of a drug versus its true, comparative effectiveness in real life. We performed a review of the literature to identify the ethical challenges thus far...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.03.005
更新日期:2015-07-01 00:00:00
abstract::Inhibition of vascular endothelial growth factor (VEGF) or its corresponding receptor (VEGFR) has been validated as an efficacious antiangiogenetic approach for cancer treatment. More recently, neuropilins (NRPs), the essential coreceptors for VEGF, have also been shown to have a significant role in VEGF signaling. Gi...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.10.004
更新日期:2019-02-01 00:00:00
abstract::Although the oral route is the most popular and acceptable way of drug administration owing to good patient compliance and safety, oral drug delivery is faced with continuous challenges regarding poorly soluble, poorly permeable or gastrointestinally unstable drugs such as proteins and polypeptides. The overall bioava...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.03.001
更新日期:2014-07-01 00:00:00
abstract::Our understanding of the detailed recognition and processing of clinically useful therapeutic agents has grown rapidly in recent years, and we are now able to begin to apply this knowledge to the rational treatment of disease. Mammalian carboxylesterases (CEs) are enzymes with broad substrate specificities that have k...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03383-0
更新日期:2005-03-01 00:00:00
abstract::The excessive release of glutamate following brain injury is responsible for the phenomenon of glutamate excitotoxicity, mediated through glutamate receptors, resulting in apoptotic cell death. KDI ameliorates excitotoxicity and regenerates damaged nerve cells. ...
journal_title:Drug discovery today
pub_type: 新闻
doi:10.1016/S1359-6446(05)03617-2
更新日期:2005-10-01 00:00:00
abstract::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(01)01877-3
更新日期:2001-08-01 00:00:00
abstract::Drug delivery systems are undergoing technology changes to enhance patient comfort and compliance. Electronic drug delivery (E-drug delivery) systems are being developed to regulate drug dose delivery by easy monitoring of doses, especially in chronic and age-related diseases. E-drug delivery can monitor the correct d...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.02.005
更新日期:2019-04-01 00:00:00
abstract::Denosumab (Dmab) was the first monoclonal antibody (mAb) approved for the treatment of osteoporosis. It blocks the receptor activator for nuclear factor κB ligand (RANKL) and acts as a potent antiresorptive agent. In contrast to classic antiresorptive agents, Dmab treatment leads to a progressive increase in bone mass...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.09.001
更新日期:2020-09-09 00:00:00
abstract::Microarray-based comparative genomic hybridization (array-CGH) has emerged as a revolutionary platform, enabling the high-resolution detection of DNA copy number aberrations. In this article we outline the use and limitations of genomic clones, cDNA clones and PCR products as targets for genomic microarray constructio...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:
更新日期:2004-12-15 00:00:00
abstract::Effective direct inhibition of adhesion receptors by small molecules has been hampered by extended receptor-ligand interfaces as well as the entropic penalties often associated with inhibition of cell adhesion. Therefore, alternative strategies have targeted enzymes that are centrally involved in the biosynthesis of r...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01581-6
更新日期:2001-01-01 00:00:00
abstract::The popularization of genomic high-throughput technologies is causing a revolution in biomedical research and, particularly, is transforming the field of drug discovery. Systems biology offers a framework to understand the extensive human genetic heterogeneity revealed by genomic sequencing in the context of the netwo...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.06.003
更新日期:2014-02-01 00:00:00
abstract::The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer - endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendoth...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.05.017
更新日期:2016-10-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) has evolved from an untreatable condition to a disease for which several classes of drugs have now been approved, including various prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Because the pathogenesis of pulmonary hypertension is increasingly u...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2008.12.003
更新日期:2009-03-01 00:00:00
abstract::Here, I provide an overview of the solid-state characteristics, phase transformations and chemical reactions of metoclopramide hydrochloride monohydrate (MCP HCl H2O). Three unique techniques, including thermoanalytical methods, one-step simultaneous differential scanning calorimetry (DSC) and Fourier transform infrar...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.10.001
更新日期:2015-02-01 00:00:00
abstract::Protein expression therapy using nucleic acid macromolecules (NAMs) as a new paradigm in medicine has recently gained immense therapeutic potential. With the advancement of nonviral delivery it has been possible to target NAMs against cancer, immunodeficiency and infectious diseases. Owing to the complex and fragile s...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.11.012
更新日期:2016-03-01 00:00:00
abstract::Since being introduced to the field of drug discovery at Zeneca Pharmaceuticals in 1991, it has become apparent to me that a blizzard of revolutionary novel approaches has swept through the pharmaceutical industry. Now, the discovery process has become completely transformed and the race to develop commercially succes...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(98)01289-6
更新日期:1999-01-01 00:00:00
abstract::Various animal models are used to study pharmacokinetics (PK) of drugs in development. Human renal clearance (CLr) should be predictable through interpolation from animal data by allometric scaling. Based on this premise, we quantified interspecies differences in CLr, and related them to drug properties. Using PubMed ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.01.018
更新日期:2020-04-01 00:00:00