Curr Opin Invest Dr
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Curr Opin Invest Dr · Sep 2005
ReviewClinical potential of nitric oxide-independent soluble guanylate cyclase activators.
A major problem with using nitrates in the treatment of ischemic heart disease is that tolerance develops to their vasodilatory actions. YC-1 was used as the lead compound to synthesize further nitric oxide-independent soluble guanylate cyclase activators, including BAY-41-2272 and BAY-41-8543. ⋯ Tolerance to the vasodilatory actions of BAY-41-8543 and BAY-58-2667 does not develop. Results from animal studies have suggested that these compounds may have potential in the treatment of ischemic heart disease, essential and pulmonary hypertension, congestive heart failure, glomerulonephritis and erectile dysfunction.
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The first cases of Ebola hemorrhagic fever were reported from Sudan and Zaire (now Democratic Republic of the Congo) in 1976, but the virus has only received significant attention since 1995. Until recently, the development of therapeutics or vaccines was not considered a priority. ⋯ Advanced understanding of the immune response has produced several vaccine candidates of which a few can be considered for further evaluation. This review will summarize and discuss the current therapeutic and prophylactic strategies for Ebola hemorrhagic fever.
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Antibody-directed enzyme prodrug therapy has demonstrated feasibility as a treatment for cancer. Numerous prodrug/drug systems have been developed for activation by a variety of enzymes and although many have shown potential in preclinical studies, so far only one system has progressed to the clinic. ⋯ The development of recombinant fusion proteins provides reproducible and effective antibody-enzyme products that retain the necessary specificity for prodrug activation. Advances in molecular, structural and systems biology, in combination with bioinformatics, have allowed these molecules to be readily manipulated to provide the desired characteristics.
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GPI-15715 (PQ-1002, Aquavan), a water-soluble prodrug of propofol, is being developed by Guilford, under license from ProQuest, as a potential anesthetic agent. In May 2004, Guilford initiated phase III trials in the US to evaluate the sedative effects of this prodrug in several patient populations.
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Curr Opin Invest Dr · Sep 2004
ReviewThe serotonin receptor and transporter as potential therapeutic targets for pulmonary hypertension.
Pulmonary hypertension (PHT) results from compromised pulmonary vasoconstriction and vascular remodeling. Serotonin (5-hydroxytryptamine/5-HT) is one of the important vasomotor agents, and its importance in the pathogenesis of PHT is currently being investigated. ⋯ Both are therefore potential therapeutic targets for the treatment of the disorder. This review describes current awareness of the roles of 5-HT, the 5-HT receptor and the 5-HTT in PHT.