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Expert Opinion on Investigational Drugs

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https://www.readbyqxmd.com/read/28521532/new-antivirals-for-the-treatment-of-chronic-hepatitis-b
#1
Vincent Soriano, Pablo Barreiro, Laura Benitez, Jose M Peña, Carmen de Mendoza
Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription...
May 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28443355/investigational-dopamine-antagonists-for-the-treatment-of-schizophrenia
#2
Sheng-Min Wang, Changsu Han, Soo-Jung Lee, Tae-Youn Jun, Ashwin A Patkar, Prakash S Masand, Chi-Un Pae
Schizophrenia is a debilitating illness with a chronic impact on social function and daily living. Although various antipsychotics are available, there are still many challenges and unmet needs. Thus, many compounds with diverse mechanisms have been investigated, but all approved antipsychotics still require interactions with dopamine D2 receptors. Areas covered: We searched for investigational drugs using the key words 'dopamine' and 'schizophrenia' in American and European clinical trial registers (clinicaltrials...
May 12, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28448171/novel-investigational-drugs-active-as-single-agents-in-multiple-myeloma
#3
Mattia D'Agostino, Marco Salvini, Antonio Palumbo, Alessandra Larocca, Francesca Gay
Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of malignant plasma cells. patient outcome has improved markedly over the last decades due to the introduction of novel therapeutic agents such as bortezomib, thalidomide and lenalidomide. However, MM still remains largely incurable and patients eventually become refractory to available treatments. To address this unmet medical need, a variety of new molecules are currently being developed in preclinical models and/or are being investigated in clinical studies...
May 8, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28446055/investigational-drugs-for-nasopharyngeal-carcinoma
#4
Brigette B Y Ma, Edwin P Hui, Anthony T C Chan
Nasopharyngeal carcinoma (NPC) is endemic to Southern China and Asia and is etiologically associated with the Epstein Barr virus (EBV). Whole exome and genome sequencing (WES, WGS) studies of NPC have reported several actionable therapeutic targets, and that the mutational load of NPC maybe comparable to that of squamous head and neck cancer. These unique biological characteristics have been exploited as potential targets and a wide range of investigational drugs are being investigated in clinical trials. Area covered: This review focused on the latest clinical development of the most promising classes of investigational agents in the treatment of advanced NPC...
May 8, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28441920/investigational-janus-kinase-inhibitors-in-development-for-myelofibrosis
#5
Prithviraj Bose, Abdallah Abou Zahr, Srdan Verstovsek
Since the discovery of the activating V617F mutation in Janus kinase 2 (JAK2), a number of pharmacologic inhibitors of JAK2 have entered clinical trials for patients with myelofibrosis. However, ruxolitinib, approved in 2011, remains the only one currently available for treatment of myelofibrosis, with many others having been discontinued for toxicity, and considerable uncertainty surrounding the future of those still in development. Areas covered: The available clinical data on pacritinib and momelotinib, the two agents in the most advanced phases of clinical testing in myelofibrosis, are examined in detail...
May 8, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28460540/drugs-in-preclinical-to-phase-ii-clinical-development-for-the-treatment-of-erectile-dysfunction
#6
Li Smith-Harrison, Nathan R Starke, Ryan P Smith, Jason R Kovac
Erectile function is an important aspect in the quality of life of many men. For men with erectile dysfunction (ED), a spectrum of treatment options exists. Novel therapies for ED are currently being developed in order to delay surgical placement of a penile prosthesis - the final step in the management of treatment-refractory ED. Areas covered: This review examines innovative treatments such as alternative vasoactive agents, trophic factors and bio-compounds as well as gene and stem cell therapy. All therapies are currently in some phase of development for the management of ED...
May 5, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28447489/forodesine-in-the-treatment-of-cutaneous-t-cell-lymphoma
#7
Daniel J Lewis, Madeleine Duvic
Cutaneous T-cell lymphoma (CTCL) is characterized by the accumulation of neoplastic CD4+ T lymphocytes in the skin. Given the lack of curative treatments for CTCL, there is a significant need for new, superior therapies. Forodesine is a transition-state analogue that inhibits purine nucleoside phosphorylase. Because it selectively targets T lymphocytes, it represents a drug of interest for the treatment of CTCL. Areas covered: Phase I/II dose-ranging studies of intravenous (IV) and oral forodesine demonstrated its activity, safety, and tolerability for refractory CTCL...
May 5, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28468519/atrasentan-for-the-treatment-of-diabetic-nephropathy
#8
Jesus Egido, Jorge Rojas-Rivera, Sebastian Mas, Marta Ruiz-Ortega, Ana Belen Sanz, Emilio Gonzalez Parra, Carmen Gomez-Guerrero
Endothelin-1 (ET-1) is the most potent vasoconstrictor, and is involved in the renal regulation of salt and water homeostasis. When produced in excess in the kidney, ET-1 promotes proteinuria and tubulointerstitial injury. There is great interest in the clinical use of endothelin receptor antagonists (ERAs) in chronic kidney disease (CKD), mainly in diabetic nephropathy (DN). Areas covered: Physiopathological actions of ET-1 on the kidney. Both dual ETAR/ETBR (bosentan) or ETAR specific endothelin antagonists (avosentan and atrasentan, among others), which have progressed to early clinical development, with particular emphasis on atrasentan...
May 4, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28441891/investigational-and-experimental-gnrh-analogs-and-associated-neurotransmitters
#9
Zeev Blumenfeld
The GnRH agonistic analogs enable for desensitizing the hypothalamo-pituitary-gonadal axis in malignant and benign conditions where minimizing the production of sex hormones, or blocking ovulation is necessary. The possible indications are prostate cancer, benign prostate hyperplasia, breast cancer, endometriosis, precocious puberty, uterine leiomyomata, assisted reproduction (ART)/in vitro fertilization (IVF), PCOS, minimizing the gonadotoxic effect of chemotherapy in young women, and possibly ovarian cancer...
May 4, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28463570/anaplastic-lymphoma-kinase-inhibitors-in-phase-i-and-phase-ii-clinical-trials-for-non-small-cell-lung-cancer
#10
Niki Karachaliou, Mariacarmela Santarpia, Maria Gonzalez Cao, Cristina Teixido, Aaron E Sosa, Jordi Berenguer, Alejandra Rodriguez Capote, Giuseppe Altavilla, Rafael Rosell
Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients. The development of acquired resistance to crizotinib represents an ongoing challenge with the central nervous system being one of the most common sites of relapse. Ceritinib and alectinib are approved second-generation ALK TKIs. Several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib, are currently in development...
May 2, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28460541/why-do-trials-for-alzheimer-s-disease-drugs-keep-failing-a-discontinued-drug-perspective-for-2010-2015
#11
Dev Mehta, Robert Jackson, Gaurav Paul, Jiong Shi, Marwan Sabbagh
There are dozens of drugs in development for AD with billions of dollars invested. Despite the massive investment in AD drugs and a burgeoning pipeline, there have been more setbacks and failures than treatment successes. Areas Covered: The classes of drugs that have failed to date include the monoclonal antibodies, the gamma secretase inhibitors, dimebon, neurochemical enhances and one tau drug. Data for these compounds was sought through pubmed search and clinicaltrials.gov search. Expert opinion: The obvious question to be posed is: Why are they failing? Is the treatment of symptomatic dementia too late? Are the therapeutic targets incorrect? Are the clinical methodologies imprecise, misleading or inaccurate? This review summarizes the drugs that have failed 2010-2015 and offers possible theories as to why they have failed...
May 2, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28406326/umeclidinium-for-the-treatment-of-uncontrolled-asthma
#12
Matteo Ferrando, Diego Bagnasco, Fulvio Braido, Ilaria Baiardini, Giovanni Passalacqua, Francesca Puggioni, Gilda Varricchi, Giorgio Walter Canonica
Smooth muscle cell contraction in the airways is the principal therapeutic target in asthmatic subjects and its insufficient treatment is often a cause of uncontrolled disease. For this reason, research has focused on targeting smooth muscle activity with anticholinergic agents, including umeclidinium. Areas covered: This review highlights the potential application of umeclidinium, a long acting muscarinic antagonist, as a novel therapeutic approach for patients with severe uncontrolled asthma, despite maximal therapy...
April 21, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28395540/olaparib-for-the-treatment-of-breast-cancer
#13
Marie Robert, Jean-Sébastien Frenel, Carole Gourmelon, Anne Patsouris, Paule Augereau, Mario Campone
Basal-like breast cancer is characterized by being triple negative and aggressive. Defects in DNA repair is a promising therapeutic target as BRCA alterations are found in 11 to 42% of these tumors, with a frequency varying according to family history and ethnicity. The oral PARP inhibitors exploit this deficiency through a synthetic lethality and are considered as promising anticancer therapies, especially in patients harboring BRCA1 or BRCA 2 mutations. Areas covered: Olaparib is one of the most widely investigated PARP inhibitors...
April 21, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28460574/the-neurogenic-compound-nsi-189-phosphate-a-novel-multi-domain-treatment-capable-of-pro-cognitive-and-antidepressant-effects
#14
Roger S McIntyre, Karl Johe, Carola Rong, Yena Lee
Alterations in neurogenic and neurotrophic processes as well as intracellular signalling cascades provides the basis for hypothesizing that neurogenic agents may be therapeutic across multiple RDoC-defined domains (e.g. positive valence systems, general cognitive processes). Moreover, using the DSM-5 taxonomy, neurogenic agents may mitigate symptoms in adults with depressive and bipolar disorders as well as individuals with cognitive disorders. Areas covered: NSI-189 is a benzylpiperizine-aminiopyridine, a novel chemical entity that stimulates neurogenesis of human hippocampus-derived neural stem cells in vitro and stimulates neurogenesis in murine hippocampus in vivo...
June 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28388280/duvelisib-a-phosphoinositide-3-kinase-%C3%AE-%C3%AE-inhibitor-for-chronic-lymphocytic-leukemia
#15
Hima V Vangapandu, Nitin Jain, Varsha Gandhi
Frontline chemotherapy is successful against chronic lymphocytic leukemia (CLL), but results in untoward toxicity. Further, prognostic factors, cytogenetic anomalies, and compensatory cellular signaling lead to therapy resistance or disease relapse. Therefore, for the past few years, development of targeted therapies is on the rise. PI3K is a major player in the B-cell receptor (BCR) signaling axis, which is critical for the survival and maintenance of B cells. Duvelisib, a PI3K δ/γ dual isoform specific inhibitor that induces apoptosis and reduces cytokine and chemokine levels in vitro, holds promise for CLL...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28388262/investigational-drugs-targeting-fibroblast-growth-factor-receptor-in-the-treatment-of-non-small-cell-lung-cancer
#16
Erika Rijavec, Carlo Genova, Giulia Barletta, Federica Biello, Giovanni Rossi, Marco Tagliamento, Maria Giovanna Dal Bello, Simona Coco, Irene Vanni, Simona Boccardo, Angela Alama, Francesco Grossi
Fibroblast growth factor receptor (FGFR) due to its central role in regulating cell survival, is a promising target for cancer therapeutics. Dysregulation of the FGFR pathway has been observed in several malignancies, including non-small cell lung cancer (NSCLC) particularly in patients with squamous histology. Areas covered: The aim of this article is to review the most relevant findings of clinical trials investigating drugs targeting FGFR pathway: such as FGFR tyrosine kinase inhibitors (TKIs), FGFR monoclonal antibodies and FGF ligand traps in NSCLC patients...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28388253/lenalidomide-in-the-treatment-of-chronic-lymphocytic-leukemia
#17
Gilad Itchaki, Jennifer R Brown
Lenalidomide is an immunomodulatory drug (IMiD) with a unique mode of action (MOA) that may vary across disease-type. It is currently approved in multiple myeloma (MM), myelodysplastic syndrome (MDS) and mantle cell lymphoma (MCL), yet is also clinically active in a host of lymphoproliferative diseases, including chronic lymphocytic leukemia (CLL). Due to its protean effects on the immune system, lenalidomide may be particularly appealing in CLL, which is distinct in its ability to evade immune recognition and cause immunosuppression...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28388242/therapeutic-targeting-of-isocitrate-dehydrogenase-mutant-aml
#18
Prajwal Boddu, Gautam Borthakur
No abstract text is available yet for this article.
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28388237/potential-beneficial-effects-of-sacubitril-valsartan-in-renal-disease-a-new-field-for-a-new-drug
#19
Guillermo Gervasini, Nicolas Roberto Robles
Patients with renal dysfunction are at a higher risk of cardiovascular disease (CVD), which often shares manifestations with heart failure (HF). Last year, the FDA approved the use of sacubitril-valsartan in patients with HF. This dual-acting agent enhances the functions of natriuretic peptides and inhibits the renin-angiotensin system. Areas covered: This review summarizes the existing preclinical and clinical studies carried out with sacubitril-valsartan (and other drugs with similar pharmacological mechanisms) in HF and hypertensive patients...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28387541/perspectives-of-her2-targeting-in-gastric-and-esophageal-cancer
#20
James N Gerson, Sam Skariah, Crystal S Denlinger, Igor Astsaturov
The blockade of HER2 signaling has significantly improved the outlook for esophagogastric cancer patients. However, targeting HER2 still remains challenging due to complex biology of this receptor in gastric and esophageal cancers. Areas covered: Here, we review complex HER2 biology, current methods of HER2 testing and tumor heterogeneity of gastroesophageal cancer. Ongoing and completed clinical research data are discussed. Expert opinion: HER2 overexpression is a validated target in gastroesophageal cancer, with therapeutic implications resulting in prolonged survival when inhibited in the front-line setting...
May 2017: Expert Opinion on Investigational Drugs
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