Current opinion in investigational drugs最新文献_第3页

Pitrakinra, a dual IL-4/IL-13 antagonist for the potential treatment of asthma and eczema. Pitrakinra，一种IL-4/IL-13双重拮抗剂，用于治疗哮喘和湿疹。

Current opinion in investigational drugs Pub Date : 2010-11-01

Sabina A Antoniu

{"title":"Pitrakinra, a dual IL-4/IL-13 antagonist for the potential treatment of asthma and eczema.","authors":"Sabina A Antoniu","doi":"","DOIUrl":"","url":null,"abstract":"In asthma, airway inflammation is driven by Th2-related cytokines, such as IL-4, IL-5 and IL-13. IL-4 and IL-13, in particular, have a major role in the development of airway hyperresponsiveness, allergen-specific IgE synthesis and airway remodeling because of their synergistic effects induced by binding to the IL-4Rα subunit. Pitrakinra (AER-001, BAY-16-9996), being developed by Aerovance, under license from Bayer, for the potential treatment of asthma and eczema, is an IL-4 mutein, which binds to the IL-4Rα subunit and prevents the inflammation induced by IL-4 and IL-13. Pitrakinra demonstrated a potent inhibitory activity on IL-4/IL-13-mediated proliferative effects in vitro and reduced allergen-induced inflammation in animal models of asthma and skin inflammation. In phase I and II clinical trials in patients with asthma, subcutaneous and inhaled (as dry powder or nebulized) formulations of pitrakinra reduced airway inflammation, with superior effects observed with inhaled formulations. At the time of publication, a phase II clinical trial with the dry powder formulation of pitrakinra was ongoing in patients with asthma. Subcutaneous pitrakinra demonstrated preliminary efficacy results in patients with atopic eczema in a phase II clinical trial and a PEGylated variant of subcutaneous pitrakinra is being investigated for this indication. Further studies are warranted to allow a better therapeutic positioning and a more detailed characterization of the efficacy and safety of pitrakinra in asthma and atopic eczema.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 11","pages":"1286-94"},"PeriodicalIF":0.0,"publicationDate":"2010-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29535266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oligonucleotides: New therapeutic approaches for asthma and chronic obstructive pulmonary disease. 寡核苷酸:治疗哮喘和慢性阻塞性肺疾病的新途径。

Current opinion in investigational drugs Pub Date : 2010-11-01

Mark Parry-Billings, Nicolay Ferrari, Rosanne Seguin

{"title":"Oligonucleotides: New therapeutic approaches for asthma and chronic obstructive pulmonary disease.","authors":"Mark Parry-Billings, Nicolay Ferrari, Rosanne Seguin","doi":"","DOIUrl":"","url":null,"abstract":"Asthma and COPD are significant lung diseases for which anti-inflammatories, including inhaled corticosteroids and leukotriene- targeted drugs, represent a key element of current therapy. Oligonucleotides comprise a diverse family of emerging drug candidates for the treatment of these diseases. There is a commonality in the chemistry of oligonucleotide drug molecules but, importantly, individual candidates are distinct in their molecular targets and also possess different mechanisms of action. Oligonucleotides may be divided in two groups based on their main mechanism of action: (i) RNA-targeting; and (ii) protein-targeting. Antisense oligonucleotides and siRNAs, both of which belong to the RNA-targeting group, and the immunostimulatory sequence-based drugs, which are members of the protein-targeting group, are progressing through clinical trials. In principle, the development of these agents is facilitated by a series of significant advantages, such as those associated with delivery to the lung via inhalation, and targeting to the site of action, resulting in reduced levels of systemic exposure. Although no oligonucleotide-based drug has been approved for the treatment of asthma or COPD, this class of compounds holds significant promise in the treatment of these two diseases. Several oligonucleotide drug candidates have been evaluated in the clinic with no significant adverse safety findings, while clinical proof of concept based on short-term inhalation protocols in challenge models in humans has also been established.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 11","pages":"1276-85"},"PeriodicalIF":0.0,"publicationDate":"2010-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29535265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Teriflunomide, an inhibitor of dihydroorotate dehydrogenase for the potential oral treatment of multiple sclerosis. 特立氟米特，一种二氢乙酸脱氢酶抑制剂，用于多发性硬化症的潜在口服治疗。

Current opinion in investigational drugs Pub Date : 2010-11-01

Alan M Palmer

{"title":"Teriflunomide, an inhibitor of dihydroorotate dehydrogenase for the potential oral treatment of multiple sclerosis.","authors":"Alan M Palmer","doi":"","DOIUrl":"","url":null,"abstract":"Teriflunomide, being developed as a potential oral treatment for multiple sclerosis (MS) by sanofi-aventis, is the active metabolite of the rheumatoid arthritis drug leflunomide. Both teriflunomide and leflunomide are inhibitors of the mitochondrial enzyme dihydroorotate dehydrogenase, which is critically involved in pyrimidine synthesis. The production of activated T-cells largely depends on de novo pyrimidine synthesis, and thus pyrimidine depletion is thought to result in the inhibition of immune cell proliferation. Therapeutic efficacy of teriflunomide has been demonstrated in vivo in an experimental autoimmune encephalomyelitis model of MS using Dark Agouti rats. In a phase II, randomized, double-blind, placebo-controlled clinical trial of patients with relapsing-remitting MS, treatment with teriflunomide reduced the number of active lesions in the brain and preliminary evidence indicated a slowing in the development of disability. Recently reported data from the phase III TEMSO clinical trial support these initial findings. Compared with current therapies, teriflunomide has the advantage of oral administration. Thus, if good efficacy is demonstrated, teriflunomide may have a role to play in the future treatment of MS.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 11","pages":"1313-23"},"PeriodicalIF":0.0,"publicationDate":"2010-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29535269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the IL-1 family members in skin inflammation. 靶向IL-1家族成员在皮肤炎症中的作用。

Current opinion in investigational drugs Pub Date : 2010-11-01

Liselotte E Jensen

引用次数: 0

Abating progressive tissue injury and preserving function after CNS trauma: The role of inflammation modulatory therapies. 减轻中枢神经系统损伤后进行性组织损伤并保持功能:炎症调节疗法的作用。

Current opinion in investigational drugs Pub Date : 2010-11-01

Damien Pearse, Kurt Jarnagin

{"title":"Abating progressive tissue injury and preserving function after CNS trauma: The role of inflammation modulatory therapies.","authors":"Damien Pearse, Kurt Jarnagin","doi":"","DOIUrl":"","url":null,"abstract":"Brain and spinal cord injuries result in cognitive and/or sensorimotor impairments that can significantly diminish the quality of life for the patient and their carers, and result in healthcare system costs totaling in the billions. The current gold-standard of acute care for spinal cord injury is to administer high doses of glucocorticoids within 8 h of injury; administration after 8 h may be without effect or detrimental to the outcome of the patient. Therefore, improved pharmacological approaches for limiting the extent of tissue damage and neurological dysfunction in the acute injury setting are urgently needed. Early intervention in CNS injury by antagonizing or controlling the post-injury inflammatory process with pharmaceutical agents is a major focus of current clinical and preclinical investigations. In this editorial overview, recent clinical trials and preclinical studies of brain and spinal cord injuries are discussed, including studies focusing on the use of broad-spectrum immunosuppressive drugs (eg, minocycline); growth factors (eg, erythropoietin); dual anti-inflammatory and anti-vasospasm drugs, such as Rho and ROCK kinase inhibitors; and broad-spectrum anti-inflammatory drugs, such as PDE4 inhibitors. These new approaches hold great promise to improve outcomes for patients with brain and spinal injuries.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 11","pages":"1207-10"},"PeriodicalIF":0.0,"publicationDate":"2010-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29561980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tralokinumab, an anti-IL-13 mAb for the potential treatment of asthma and COPD. Tralokinumab，一种抗il -13单抗，用于治疗哮喘和COPD。

Current opinion in investigational drugs Pub Date : 2010-11-01

Garry M Walsh

引用次数: 0

The growth receptors and their role in wound healing. 生长受体及其在伤口愈合中的作用。

Current opinion in investigational drugs Pub Date : 2010-11-01

Kerstin J Rolfe, Adriaan O Grobbelaar

引用次数: 0

Targeting Th2 cytokines in fibrotic diseases. 靶向Th2细胞因子治疗纤维化疾病。

Current opinion in investigational drugs Pub Date : 2010-11-01

Yuko Morishima, Yukio Ishii