IDrugs : the investigational drugs journal
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Remimazolam (CNS-7056) is a short-acting GABA(A) receptor agonist, under development by PAION, in collaboration with Japanese licensee Ono Pharmaceutical, as an intravenous sedative agent for potential use in day-case procedures, and the induction and maintenance of anesthesia. A member of the benzodiazapene class of drugs, the structure of remimazolam was modified to produce a drug that displays organ-independent metabolism. ⋯ In a phase IIa clinical trial evaluating remimazolam as a procedural sedative for upper gastrointestinal endoscopy in patients, the time to recovery from sedation was shorter and more consistent with remimazolam, relative to midazolam. Because of its organ-independent metabolism and rapid and predictable onset and recovery, remimazolam appears to have potential advantages over other currently available short-acting sedatives.
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Tyrosine kinase receptors have important signaling functions in various physiological and pathological pathways. The recognition of their involvement in tumor angiogenesis, which is the main event of tumor progression, opened a new era in the discovery of anticancer drugs. Developers soon grasped that by targeting several tyrosine kinase receptors at once, so-called multitarget tyrosine kinase inhibitors, a drug could dramatically affect the progression of cancer and decrease resistance. ⋯ The sustained inhibition of VEGFR phosphorylation (> 24 h), the fast in vivo clearance and clinical efficacy against a broad range of malignancies appear to be the major advantages of intedanib. Furthermore, the existing data suggest an excellent safety profile. At the time of publication, intedanib had reached phase III trials for the treatment of NSCLC and ovarian cancer.
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The productivity of the pharmaceutical industry, as assessed by the number of NMEs produced per US dollar spent in R&D, has been in steady decline during the past 40 years. This decline in productivity not only poses a significant challenge to the pharmaceutical industry, but also to society because of the importance of developing drugs for the treatment of unmet medical needs. The major challenge in progressing a new drug to the market is the successful completion of clinical trials. ⋯ However, open-access collaborative partnerships are gaining momentum in industry, and are also favored by funding agencies. Such open-access collaborations may be a powerful alternative to closed collaborations; the sharing of early-stage research data is expected to enable scientific discovery by engaging a broader section of the scientific community in the exploration of new findings. Potentially, the sharing of data could contribute to an increased understanding of biological processes and a decrease in the attrition of clinical programs.
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The HER-2/neu oncoprotein is an important cellular target for the development of a variety of targeted therapies for HER-2/neu-positive breast cancer. Methods for tumor analysis such as immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) are routinely used to determine the HER-2/neu status of patients with breast cancer and their eligibility for HER-2/neu-targeted therapies, such as trastuzumab (Herceptin) and lapatnib (Tykerb). In a January 2008 article in the Wall Street Journal, it was reported that breast cancer patients may be receiving the wrong treatments or no treatment because of errors in the laboratory tests (IHC/FISH) that are widely used to determine the HER-2/neu status of breast cancers. ⋯ Thus, the number of patients classified incorrectly as HER-2/neu negative could be substantially greater than recognized previously. This feature review presents a HER-2/neu testing algorithm that combines the serum HER-2/neu test result with IHC/FISH test results to maximize the identification of patients who are HER-2/neu positive and could be potential candidates for HER-2/neu-targeted therapies. The HER-2/neu situation also exemplifies that multiple diagnostic tools are required to correctly and accurately identify patients for targeted therapies--an important lesson as many new biomarkers are identified for the multitude of new targeted therapies in development for various forms of cancers.