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Expert Opinion on Investigational Drugs

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https://www.readbyqxmd.com/read/30227753/investigational-drugs-targeting-prostaglandin-receptors-for-the-treatment-of-glaucoma
#1
Artemis Matsou, Eleftherios Anastasopoulos
Prostaglandin F2α analogues were the first prostaglandin agonists introduced for glaucoma treatment. Thanks to their efficacy and favourable tolerability they set a high bar in competition, with a resultant paucity in new hypotensive drug development for many years. However, the scientific community has shown recently a new interest in exploring new options for glaucoma treatment, generating a remarkable incentive in the marketplace for new drugs. Areas covered: This article reviews agents targeting prostaglandin receptors that are currently being investigated for glaucoma treatment...
September 19, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30223692/the-early-pre-clinical-and-clinical-development-of-ganaplacide-kaf156-a-novel-antimalarial-compound
#2
Robin Koller, Ghyslain Mombo-Ngoma, Martin P Grobusch
Ganaplacide (previously known as KAF156) is a novel antimalarial compound part of the imidazolopiperazine family. Areas covered: At the time of writing, a total of 8 studies addressing its pre-clinical and clinical development have been published on this compound, which is currently in phase 2 of clinical development, alongside lumefantrine in a novel soluble formulation as combination partner. This review provides an overview and interpretation of the published pre-clinical and clinical data of this possible next-generation antimalarial drug...
September 18, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30196727/targeted-agents-for-her2-positive-breast-cancer-in-older-adults-current-and-future-perspectives
#3
Enrique Soto-Perez-de-Celis, Kah Poh Loh, Capucine Baldini, Nicolò Matteo Luca Battisti, Yanin Chavarri-Guerra, Nienke A De Glas, Tina Hsu, Arti Hurria
A third of breast cancer cases worldwide occur in women aged 65 years and older, with 10 to 15% overexpressing the human epidermal growth factor receptor 2 (HER2). Although several HER2-targeted therapies have been developed, the lack of data regarding their use in older patients hampers evidence-based decision-making for this population. Areas Covered: We review current evidence on the efficacy and safety of HER2-targeted therapies in older adults with breast cancer, focusing on approved therapies such as trastuzumab, lapatinib, pertuzumab, ado-trastuzumab-emtansine, and neratinib...
September 9, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30148648/new-concepts-in-opioid-analgesia
#4
Christoph Stein
Opioids are the oldest and most potent drugs for the treatment of severe pain, but they are burdened by detrimental side effects such as respiratory depression, addiction, sedation, nausea, and constipation. Their clinical application is undisputed in acute (e.g. perioperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny and has contributed to the current 'opioid crisis.' Areas covered: This article reviews pharmacological principles and research strategies aiming at novel opioids with reduced side effects...
September 7, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30118330/investigational-therapies-targeting-the-androgen-signaling-axis-and-the-androgen-receptor-and-in-prostate-cancer-recent-developments-and-future-directions
#5
Pedro Isaacsson Velho, Michael A Carducci
Despite the heterogeneity of prostate cancer (PCa), androgen stimulation is fundamental to its development, growth, and lethality. Therefore, the blockade of androgen receptor (AR) signaling is critical to controlling the disease, even after progression with castrate levels of androgens. Areas covered: We review the current understanding of new ways to block the AR, using novel antiandrogen inhibitors, which act on different parts of the AR signaling pathway in PCa. We also review new approaches, such as the use of poly(ADP-ribose) polymerase (PARP) inhibitors, targeting both the AR and the DNA repair pathway, potentially adding synergy and improving efficacy and the combination of AR inhibitors and immunotherapy...
August 31, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30056776/investigational-drugs-in-phase-i-and-phase-ii-clinical-trials-targeting-interleukin-23-il23-for-the-treatment-of-crohn-s-disease
#6
Christopher Ma, Vipul Jairath, Reena Khanna, Brian G Feagan
Medical therapy for Crohn's disease (CD) is directed at controlling intestinal inflammation to prevent development of disease-related complications. Not all patients will respond to currently available treatments and thus, novel therapies are needed. The interleukin (IL)-23 cytokine axis is implicated in CD pathogenesis and so targeting this pathway has become an important focus for drug development. Areas covered: This review summarizes the role of the IL23 cytokine pathway in CD pathogenesis and appraises phase I and II clinical trial data for novel IL23p19 specific monoclonal antibodies for the treatment of CD...
August 10, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30084282/investigational-chk1-inhibitors-in-early-stage-clinical-trials-for-acute-myeloid-leukemia
#7
Kamal Chamoun, Gautam Borthakur
Acute myeloid leukemia (AML) is the most common myeloid malignancy in adults. Despite recent discoveries of targeted therapies, the frontline therapy consisting of chemotherapy remains unchanged for the past four decades. Like other cancers, AML is characterized by deranged DNA damage repair (DDR) pathway. Although impaired DDR may contribute to the pathogenesis of AML it also allows leukemia cells with damaged DNA to attempt repair resulting in resistance. CHK1 inhibitors reverse the cell cycle arrest, disallowing the cell to repair the chemotherapy-induced DNA damage, driving the cell to enter into mitotic catastrophe...
August 7, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30019949/investigational-drug-therapies-in-phase-i-and-phase-ii-clinical-trials-for-alcohol-use-disorders
#8
Leigh C Walker, Andrew J Lawrence
Alcohol use disorder (AUD) is a complex psychiatric condition characterized by craving, compulsive seeking, loss of control of alcohol consumption as well as the emergence of negative emotional states during withdrawal. Despite the large socioeconomic burden of AUD, therapeutic treatment options lag behind. Areas covered: This review covers pharmacotherapies currently in phase I/II clinical trials for the treatment of AUDs listed on clinicaltrials.gov. We discuss drug therapies that modulate monoamine, GABA/Glutamate, neuropeptide and neuroimmune systems...
July 27, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30142984/testing-biologics-and-intracellular-signaling-inhibitors-on-pediatric-atopic-dermatitis-a-stairway-to-modern-therapeutic-approaches
#9
REVIEW
Andrea Chiricozzi, Diego Peroni, Giampiero Girolomoni
Atopic dermatitis (AD) is the most common cutaneous inflammatory disease in adults and children. In the last few years, the pathogenesis of AD has been profoundly revised, and this has led to the identification of novel druggable targets and the development of new agents targeting specific molecular pathways. Despite the high prevalence of AD in the pediatric population, the clinical development of new treatments, either topical or systemic, has been focused on the adult population in recent years; only a limited number of these new agents have been tested in pediatric cohorts...
September 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30130132/update-on-the-effects-of-the-sodium-pump-%C3%AE-1-subunit-on-human-glioblastoma-from-the-laboratory-to-the-clinic
#10
REVIEW
Yu-Long Lan, Zhen-Long Yu, Jia-Cheng Lou, Xiao-Chi Ma, Bo Zhang
Glioblastoma is a debilitating disease that is associated with poor prognosis and a very limited response to therapies; thus, molecularly targeted therapeutics and personalized therapy are urgently needed. The Na+ /K+ -ATPase sodium pump is a transmembrane protein complex that has recently been recognized as an important transducer and integrator of various signals. The sodium pump α1 subunit, which is highly expressed in most glioblastomas compared with that in normal brain tissues, is an emerging cancer target that merits further investigation...
September 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30124336/novel-targeted-treatment-options-for-advanced-cholangiocarcinoma
#11
REVIEW
Amit Mahipal, Anuhya Kommalapati, Sri Harsha Tella, Alexander Lim, Richard Kim
Surgical resection remains the mainstay of potentially curative treatment in the early stages of cholangiocarcinoma, whereas for the advanced stage, systemic chemotherapeutics and experimental targeted therapies are the primary treatment options. The molecular heterogeneity of the tumor is based on location, liver dysfunction, and relative rarity of the disease and confers challenges for clinical trial enrollment. The advancements in the understanding of molecular pathogenesis of cholangiocarcinoma have led to the development of targeted therapies that are currently being evaluated in the clinical trials...
September 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30118336/the-advances-in-therapy-of-blastic-plasmacytoid-dendritic-cell-neoplasm
#12
REVIEW
Daniel Kerr, Lubomir Sokol
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy that contributes to <1% of all hematologic neoplasms. Before the introduction of various targeted agents, the therapeutic approach was based on regimens used for acute lymphoblastic or myeloid leukemia and non-Hodgkin's lymphoma (e.g. hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high dose methotrexate and cytarabine) and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) -based regimens) followed by allogeneic stem cell transplantation for eligible patients...
September 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30111181/patterns-of-antibody-response-during-natural-hrsv-infection-insights-for-the-development-of-new-antibody-based-therapies
#13
REVIEW
Natalia Muñoz-Durango, Magdalena S Pizarro-Ortega, Emma Rey-Jurado, Fabián E Díaz, Susan M Bueno, Alexis M Kalergis
The human respiratory syncytial virus (hRSV) is the main cause of acute lower respiratory tract infection in susceptible population worldwide, such as young children and the elderly. Although hRSV is a major public health burden, there are no licensed vaccines and the only available therapy is palivizumab. During life, reinfections with hRSV are common, suggesting that the virus can impair the development of an efficient host immune response. This feature has hindered the development of efficient therapies...
September 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30102076/strategic-development-of-azd1775-a-wee1-kinase-inhibitor-for-cancer-therapy
#14
REVIEW
Siqing Fu, Yudong Wang, Khandan Keyomarsi, Funda Meric-Bernstein
Wee1 kinase controls the G2-M checkpoint. Wee1 inhibition by AZD1775 allows cells with a deregulated G1 checkpoint to progress, resulting in catastrophe and apoptosis. The challenges ahead are in the establishment of the optimum dosing schedule either alone or in combination and the identification of patients with specific biomarker profiles who benefit most. Areas covered: This article provides an overview of AZD1775, based on English peer-reviewed articles on MEDLINE. The authors highlight the data from the published preclinical and clinical studies...
September 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30058384/investigational-drugs-for-atopic-dermatitis
#15
REVIEW
Kam Lun Hon, Alexander K C Leung, Theresa N H Leung, Vivian W Y Lee
Many novel medications and herbal medicines have claimed efficacy on atopic dermatitis (AD). Areas covered: This review covers evidence on efficacy of topical and oral forms of novel and investigational drugs. Topical agents include emollients, phosphodiesterase E4 (PDE4) inhibitors, and topical herbs. There is little evidence that ceramides or natural moisturizing factors provide relief in AD. PDE4 inhibitors have shown promise as an effective topical treatment for mild-to-moderate AD with minimal adverse events, and dupilumab as an effective subcutaneous agent for the treatment of moderate-to-severe AD in adult patients with little adverse effects...
August 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30019966/n-acetyl-cysteine-in-the-treatment-of-alcohol-use-disorder-in-patients-with-liver-disease-rationale-for-further-research
#16
REVIEW
Kirsten C Morley, Andrew Baillie, Wim Van Den Brink, Kate E Chitty, Kathleen Brady, Sudie E Back, Devanshi Seth, Greg Sutherland, Lorenzo Leggio, Paul S Haber
Alcoholic liver disease (ALD) is the leading cause of alcohol-related death and one of the most common forms of liver disease. Abstinence from alcohol is crucial to reducing morbidity and mortality associated with the disease. However, there are few pharmacotherapies for alcohol use disorder suitable for those with significant liver disease. Areas Covered: This paper presents a rationale for investigating the use of N-acetyl cysteine (NAC) to promote abstinence or reduce heavy alcohol consumption for patients with an alcohol use disorder, particularly in the presence of liver disease...
August 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/30001170/iph4102-a-monoclonal-antibody-directed-against-the-immune-receptor-molecule-kir3dl2-for-the-treatment-of-cutaneous-t-cell-lymphoma
#17
REVIEW
Carrie Van Der Weyden, Martine Bagot, Paul Neeson, Phil K Darcy, H Miles Prince
Therapeutic options for mycosis fungoides and Sézary syndrome include a variety of immunomodulatory, epigenetic, and cytotoxic options; however, none has been demonstrated to be efficacious for all patients, or to deliver deep and durable responses to the majority of patients. In this review, we examine the monoclonal antibody, IPH4102, a novel agent for the treatment of cutaneous T-cell lymphoma. Areas covered: In this review, we examine data demonstrating the tissue specificity of KIR3DL2 receptor, which is highly expressed on the malignant cells in cutaneous T-cell lymphoma, including mycosis fungoides and Sézary syndrome...
August 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29985060/pf-00547659-for-the-treatment-of-crohn-s-disease-and-ulcerative-colitis
#18
REVIEW
Mariangela Allocca, Daniela Gilardi, Gionata Fiorino, Federica Furfaro, Marjorie Argollo, Laurent Peyrin-Biroulet, Silvio Danese
Gut-specific homing is mainly mediated by the expression of MAdCAM-1 on endothelial cells. An increase in MAdCAM-1 expression has been shown in patients with inflammatory bowel disease (IBD). Areas covered: PF-00547659 is a fully human monoclonal antibody (mAb) toward MAdCAM-1 on endothelial cells, blocking its binding with the α4β7 integrin on leukocytes. This review discusses the available data on effectiveness and safety of PF-00547659 in IBD. Expert opinion: A phase II study in moderate-to-severe ulcerative colitis (UC) patients, both naïve and previously exposed to anti-tumor necrosis factors, showed that PF-00547659 was superior to placebo for induction of remission, response, and mucosal healing at week 12...
July 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29975110/investigational-hypoxia-inducible-factor-prolyl-hydroxylase-inhibitors-hif-phi-for-the-treatment-of-anemia-associated-with-chronic-kidney-disease
#19
REVIEW
Lucia Del Vecchio, Francesco Locatelli
In the last decade, concerns have been raised around the use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in chronic kidney disease (CKD) patients, especially when given at high doses. Moreover, treatment with ESA is expensive. Areas covered: We searched PubMed for original articles, reviews, and editorials having as a topic anemia, CKD, hypoxia inducible factor, hepcidin, iron, and hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). HIF-PHI are a new class of small molecules activating HIF-alfa isoforms (the main mediators of the effects of hypoxia on the body)...
July 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29972333/senolytic-drugs-in-respiratory-medicine-is-it-an-appropriate-therapeutic-approach
#20
REVIEW
Mario Cazzola, Maria Gakriella Matera, Paola Rogliani, Luigino Calzetta
Aging is the major risk factor for most of the chronic diseases. Cellular senescence is one of the main hallmarks of aging. A growing body of evidence implicates accelerated mechanisms of aging, including cellular senescence, in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) pathogenesis. Senolytics are pharmaceutical agents that eliminate senescent cells, thus blocking tissue degeneration and late life complications and allowing tissue regeneration. Areas covered: The potential use of senolytic drugs in respiratory medicine is examined and discussed...
July 2018: Expert Opinion on Investigational Drugs
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