Abstract：
:Options for disease-modifying therapies in multiple sclerosis have increased over the past two decades. Among these innovations are interferon-β, glatiramer acetate, fumaric acid and dihydroorotate dehydrogenase inhibitors, an antibody targeting the migration of immune cells, a compound that traps immune cells in lymphoid organs by sphingosine 1-phosphate receptor (S1PR) modulation and immune-reconstitution therapies. Second-generation drugs such as pegylated interferon-β, advanced CD20 depleting antibodies, more-specific S1PR modulators and new formulations have been developed to achieve higher efficacy while exhibiting fewer side effects. In this review, we address the shortcomings of the parent drugs, present the pros and cons of the second-generation therapies and summarize upcoming developments in the field of immunotherapy for multiple sclerosis.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Findling O,Sellner Jdoi
10.1016/j.drudis.2020.11.022subject
Has Abstractpub_date
2020-11-25 00:00:00eissn
1359-6446issn
1878-5832pii
S1359-6446(20)30504-3pub_type
杂志文章,评审abstract：:Current advances in systems biology suggest a new change of paradigm reinforcing the holistic nature of the drug discovery process. According to the principles of systems biology, a simple drug perturbing a network of targets can trigger complex reactions. Therefore, it is possible to connect initial events with final...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.02.004
更新日期：2017-07-01 00:00:00
abstract：:The blood-brain barrier (BBB) hinders the accumulation of active compounds in the central nervous system, thus decreasing their therapeutic effectiveness. To overcome this obstacle, interesting supramolecular nanodevices are herein considered. These systems have many advantages over the conventional formulations, such...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.02.006
更新日期：2011-04-01 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：:The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are ligand-activated nuclear receptors (NRs) that are notorious for their role in drug metabolism, causing unintended drug-drug interactions and decreasing drug efficacy. They control the xenobiotic detoxification system by regulating the exp...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.01.021
更新日期：2019-03-01 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：:Inhibitors of epigenetic targets have entered clinical trials with some success, in particular for combined therapies. Like many other chemotherapeutics these new classes of molecules have dose-limiting toxicities and highly active metabolism in vivo resulting in lower efficacy than expected. This review presents drug...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.03.017
更新日期：2014-09-01 00:00:00
abstract：:Osteoarthritis (OA), the most common and disabling form of arthritic disease, is characterized by a slow and progressive degeneration of articular cartilage. Its etiology is multifactorial and includes genetic predisposition, obesity and aging. In addition to the cartilage itself, OA also involves the surrounding tiss...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.01.004
更新日期：2011-05-01 00:00:00
abstract：:Immunoinformatics has recently emerged as a critical field for accelerating immunology research. Although still an evolving process, computational models now play instrumental roles, not only in directing the selection of key experiments, but also in the formulation of new testable hypotheses through detailed analysis...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.04.001
更新日期：2009-07-01 00:00:00
abstract：:The biopharmaceutical industry has undergone remarkable changes over the past half century, driven largely by a need to offset the ever-rising costs of developing new medicines. In this report, we aggregated information about the creation and fate of all clinical-stage biopharmaceutical companies, assessing trends ove...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.10.026
更新日期：2021-01-01 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：:Intravitreal injection is one of the major administration routes for the treatment of posterior ocular diseases. Intravitreal therapeutics usually suffer from unsatisfactory efficacy owing to fast clearance from the vitreous humour and insufficient distribution into the retina. Engineered nanoparticles have been appli...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.05.005
更新日期：2019-08-01 00:00:00
abstract：:To maintain orphan drug status at the time of market authorization, orphan medicinal products (OMPs) need to be assessed for all criteria, including significant benefit, by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA). Subsequently, health technology assessment (HTA) organi...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2020.04.012
更新日期：2020-07-01 00:00:00
abstract：:Wnt/β-catenin signaling is an evolutionarily conserved signaling cascade with imperative roles during development and in adult stem cell maintenance. Hyperactivation of Wnt/β-catenin drives various cancers, whereas hypoactivation underlies bone malformations and neurodegenerative disorders. Although several small mole...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2010.11.007
更新日期：2011-01-01 00:00:00
abstract：:Over the past three decades, statins have become the cornerstone of prevention and treatment of atherosclerotic cardiovascular and metabolic diseases. Albeit generally well tolerated, these drugs can elicit a variety of muscle-associated symptoms that represent the most important reason for treatment discontinuation. ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.09.001
更新日期：2017-01-01 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：:Application of humanized xenotransplantation disease models and experimental clinical studies in the context of translational research in drug discovery in dermatology is an opportunity to reduce failure due to lack of efficacy in clinical development stage. ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.10.009
更新日期：2008-03-01 00:00:00
abstract：:A reduction in intraocular pressure (IOP) is the only recognized therapy for glaucoma. Hence, drugs exhibiting ocular hypotensive effects are important targets for antiglaucomatous drug development. IOP is determined by the equilibrium of aqueous humor production and outflow through either the trabecular meshwork or t...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.05.033
更新日期：2019-08-01 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：:Total-body exposure to ionizing radiation (TBI) results in life-threatening acute radiation syndrome (ARS), which encompasses hematopoietic and gastrointestinal (GI) injuries and results in dose-dependent morbidity and mortality. Management of ARS warrants the deployment of effective medical countermeasure agents (MCM...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.02.004
更新日期：2020-04-01 00:00:00
abstract：:Polymer-drug conjugates (PDC) have exhibited clinical and commercial success in the field of drug delivery. A polymeric backbone, linker, targeting moiety, and drug constitute the building blocks of PDCs. Current attention is focusing on natural polymeric carriers, in particular the concept of graft copolymers, such a...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.06.028
更新日期：2020-09-01 00:00:00
abstract：:The p53 family proteins are among the most appealing targets for cancer therapy. A deeper understanding of the complex interplay that these proteins establish with murine double minute (MDM)2, MDMX, and mutant p53 could reveal new exciting therapeutic opportunities in cancer treatment. Here, we summarize the most rele...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.02.007
更新日期：2016-04-01 00:00:00
abstract：:An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2017.06.011
更新日期：2017-11-01 00:00:00
abstract：:The successful cloning and subsequent clinical application of recombinant cytokines and/or growth factors has generated a number of important therapeutics. In contrast to the G-protein-coupled receptors, identification of small-molecule agonists of the cytokine and/or growth factor receptor family has proved difficult...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(00)00062-3
更新日期：2000-12-01 00:00:00
abstract：:Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly involving the selective and progressive loss of dopaminergic neurons from the substantia nigra, resulting in motor and non-motor symptoms. PD remains an incurable ailment; thus, treatments are limited to symptom alleviation...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.09.004
更新日期：2019-11-01 00:00:00
abstract：:Recent groundbreaking work in genetics has identified thousands of small-effect genetic variants throughout the genome that are associated with almost all major diseases. These genome-wide association studies (GWAS) are often proposed as a source of future medical breakthroughs. However, with several notable exception...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2015.05.012
更新日期：2015-10-01 00:00:00
abstract：:Pharmacological modulation of intracellular cyclic AMP (cAMP) signalling could provide new therapeutic and experimental tools. Although drugs interfering with this pathway have traditionally targeted membrane receptors, the effector enzyme adenylyl cyclase (AC), which functions as a signalling catalyst, also presents ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.07.007
更新日期：2009-10-01 00:00:00
abstract：:Patients with severe asthma suffer persistent symptoms and/or frequent exacerbations despite high-intensity treatment. Their severe unrelenting symptoms have a huge impact on healthcare resources owing to frequent hospital admissions and requirement for intensive treatments. Consequently, there is an undeniable need f...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.01.012
更新日期：2012-06-01 00:00:00
abstract：:We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2015.06.015
更新日期：2015-11-01 00:00:00
abstract：:Successful strategies for the development of monoclonal antibodies require integration of knowledge with respect to target antigen properties, antibody design criteria such as affinity, isotype selection, Fc domain engineering, PK/PD properties and antibody cross-reactivity across species from the early stages of anti...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.12.008
更新日期：2009-03-01 00:00:00
abstract：:The development of tissue-engineering (TE) solutions for osteochondral (OC) regeneration has been slowed by technical hurdles related to the recapitulation of their complex and hierarchical architecture. OC defects refer to damage of both the articular cartilage and the underlying subchondral bone. To repair an OC tis...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.01.008
更新日期：2018-03-01 00:00:00
