Expert opinion on investigational drugs
-
Expert Opin Investig Drugs · Mar 2012
ReviewThe therapeutic potential of GPR119 agonists for type 2 diabetes.
Patients with type 2 diabetes mellitus (T2DM) are reaching an explosive number. Pancreatic β cell dysfunction is the characteristic feature of the progression of T2DM and there is an increasing need for agents to improve its function. GPR119 is a G protein-coupled receptor (GPCR) expressed both in pancreatic β cells and enteroendocrine cells and has garnered significant interest as a promising target for the next generation of T2DM drug. In vitro studies indicate that GPR119 agonists increase intracellular cAMP levels leading to enhanced glucose-induced insulin release and enhanced incretin hormone glucagon-like peptide 1 (GLP-1) secretion. In T2DM rodent models, GPR119 agonists are shown to decrease blood glucose level and preserve pancreatic β cell function. ⋯ GPR119 agonists with glucose-dependent insulin release and increased insulin promoter activity is expected to preserve pancreatic β cell function, thereby providing great clinical benefits for T2DM patients. Both the preclinical and clinical data suggest that GPR119 agonist will be a promising anti-diabetic drug.
-
Expert Opin Investig Drugs · Feb 2012
ReviewBrentuximab Vedotin (SGN-35), an antibody-drug conjugate for the treatment of CD30-positive malignancies.
CD30-positive hematological malignancies are potentially curable with frontline combination chemotherapy regimens; however, those patients who relapse or are refractory to initial therapies have less favorable prognosis. ⋯ These data support an expanded development program for brentuximab vedotin in multiple CD30-positive indications.
-
Expert Opin Investig Drugs · Feb 2012
ReviewMisoprostol for the prevention and treatment of postpartum hemorrhage.
Uterotonic drugs are recommended for the prevention and treatment of postpartum hemorrhage (PPH), and oxytocin is considered the gold standard for both indications due to its established efficacy and safety. Unfortunately, access to oxytocin is still limited in many low-resource settings due to the need for cool storage, sterile equipment and administration by skilled personnel. Misoprostol , an E1 prostaglandin analog, has therefore been explored as an alternative for such settings due to its proven ability to induce uterine contractions, low cost, stability at room temperature and ease of administration. ⋯ There is now a solid body of evidence to justify the use of misoprostol for postpartum hemorrhage indications in many settings. The evidence supports use of 600 μg orally for the prevention of PPH and 800 μg sublingually for the treatment of PPH. There is no evidence to support the adjunct use of misoprostol following administration of conventional uterotonics for prevention or treatment purposes.
-
Expert Opin Investig Drugs · Jan 2012
ReviewImatinib mesylate for the treatment of pulmonary arterial hypertension.
Despite recent advances, pulmonary arterial hypertension (PAH) remains a devastating disease which harbors a poor prognosis. Novel therapeutic approaches directly targeting pulmonary vascular remodeling are warranted. ⋯ PDGF is a potent mitogen for pulmonary vascular smooth muscle cells and represents an important mediator of pulmonary vascular remodeling. Imatinib mesylate, a compound that inhibits the Bcr-Abl kinase and was developed for the treatment of chronic myeloid leukemia, also targets PDGF receptors. Both experimental and clinical data indicate that it reverses the vascular remodeling process even when it is fully established. Results from Phase II and III clinical trials suggest potent and prolonged efficacy in patients with severe PAH (i.e., pulmonary vascular resistance > 800 dynes*s*cm(-5)). Future studies should evaluate the long-term clinical efficacy and safety of imatinib, including patients with less impaired hemodynamics. Based on the current knowledge, this compound is likely to become an additional treatment option for patients with PAH and has the potential to at least partially correct the pathology of the disease.
-
Expert Opin Investig Drugs · Jan 2012
ReviewInvestigational NMDA receptor modulators for depression.
With regards to depression, the role of N-methyl-D-aspartate receptor (NMDA) was pursued many years ago, mainly in the form of preclinical studies. Since then, there have been several clinical data in the literature indicating the efficacy of NMDA receptor antagonists of either stand-alone or as an adjunct therapy in depression and depression-related diseases. ⋯ Several NMDA receptor modulators have been tested in both human and animal studies to examine their potential antidepressant activity. Most of the compounds that exhibited beneficial properties in the animal tests and models of depression either have never been tested or did not show efficacy in humans. For some of them, such as ketamine, where a consistently reproducible antidepressant effect was found, clinical use is limited by a variety of adverse effects. However, ketamine has become a standard tool for identifying the biological factors associated with rapid antidepressant action and, as such, is a novel target for the development of new therapeutics.