Curr Opin Invest Dr
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Curr Opin Invest Dr · Nov 2008
ReviewThe role of sphingosine-1-phosphate and ceramide-1-phosphate in calcium homeostasis.
During the last several years, sphingolipids have been identified as a source of important signaling molecules. Particularly, the understanding of the distinct biological roles of ceramide, sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P) and lyso-sphingomyelin in the regulation of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking has rapidly expanded. ⋯ This review focuses on the role of S1P and C1P in maintaining Ca2+ homeostasis. By studying changes in the metabolism of S1P and C1P in pathological conditions, it is hoped that altered sphingolipid-metabolizing enzymes and their metabolites can be used as therapeutic targets.
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Curr Opin Invest Dr · Jul 2008
ReviewCasopitant, a neurokinin-1 receptor antagonist with anti-emetic and anti-nausea activities.
Casopitant, an inhibitor of the neurokinin-1 receptor, and its mesylate salt, are being developed by GlaxoSmithKline plc for the potential treatment of chemotherapy-induced nausea and vomiting (CINV), post-operative nausea and vomiting (PONV), as well as for anxiety, depression and insomnia. Phase II trials are ongoing for anxiety, depression and insomnia, and further results are awaited from phase III trials of CINV and PONV. At the time of publication, it was expected that applications to the FDA for regulatory approval for CINV and PONV would be filed in 2008. Casopitant was previously being developed for the treatment of overactive bladder; however, in September 2007, this indication was no longer listed on the company's product pipeline.
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Curr Opin Invest Dr · Jul 2008
ReviewNeuroimmune interactions and pain: focus on glial-modulating targets.
Chronic pain is the most difficult type of pain to treat. Previously, the development of analgesics has focused on neuronal targets; however, current analgesics are only modestly effective, have significant side effects and do not provide universal efficacy. ⋯ Glial cells have integral roles in CNS homeostasis, and chronic pain etiology and progression. In this review, the role of glia in neuropathic pain and opioid administration is described, as well as the potential superior efficacy and wider therapeutic indices provided by drugs that modulate specific glial function via novel targets.
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Curr Opin Invest Dr · Jul 2008
ReviewMorphine-6-glucuronide, an active morphine metabolite for the potential treatment of post-operative pain.
Morphine-6-glucuronide (M6G) is an active metabolite of morphine that is being developed by CeNeS Pharmaceuticals as an alternative to morphine (the most commonly used opioid) for the management of postoperative pain. M6G is currently undergoing phase III clinical trials in patients with postoperative pain.
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Curr Opin Invest Dr · Jun 2008
ReviewAEG-35156, an antisense oligonucleotide against X-linked inhibitor of apoptosis for the potential treatment of cancer.
Aegera, under license from Idera Pharmaceuticals, is developing AEG-35156, a 19-mer phosphorothioate antisense oligonucleotide targeting the caspase inhibitor X-linked inhibitor of apoptosis protein (XIAP) messenger RNA, for the potential treatment of cancer. Several clinical trials are ongoing and include: two phase I monotherapy clinical trials for the potential treatment of cancer and in patients with solid tumors; a phase I combination clinical trial of AEG-35156 with docetaxel in locally advanced, metastatic, or recurrent solid tumors; four phase I/II combination clinical trials for the potential treatment of pancreatic cancer, advanced breast cancer, advanced NSCLC, and acute myeloid leukemia. Mild to moderate adverse effects were observed in early phase clinical trials. Aegera plans to initiate randomized phase III trials if tolerable side effects and evidence of activity are demonstrated in phase I/II clinical trials.