The discovery of an inducible form of cyclooxygenase (COX) stimulated the search for new, isolom-... more The discovery of an inducible form of cyclooxygenase (COX) stimulated the search for new, isolom-selective inhibitors that culminiated in the introduction of an entirely new generation of antiinfiammatory drugs with improved gestrointestinal tolerability. Cimicoxib (UR-6880), a new imidazole derivative, is a highly selective COX-2 inhibitor that exhibite promising antiinflammatory and analgesic activity. The compound showed good oral activity when tested in experimental models of acute and chronic inflammation and pain, comparable to celecoxib and rotecoxib. Cimicoxib exhibited a good phamacokinetic profile in rats and dogs and a high satety margin as regards both the cardiorespiratory and central nervous systems. In humans, cimicoxib appeared to be safe and well tolerated at doses up to 600 mg. After repeated administration the compound was sale and well tolerated up to 100 mg and there was no significant accumulation after 12 doses. In subjects with moderate to severe postoperativ...
Approximately half of the U.S. adult population suffers from insomnia, with a higher incidence se... more Approximately half of the U.S. adult population suffers from insomnia, with a higher incidence seen in the elderly. The benzodiazepines, sedative/hypnotic drugs which shorten sleep onset latency and increase sleep continuity, have been the standard treatment for insomnia. However, these agents also suppress REM and deep sleep and are associated with unwanted effects such as memory impairment, next-day residual sedation and alteration of hormonal secretion. Another pharmacotherapeutic option for the treatment of insomnia are the nonbenzodlazepines which are seiective for the BZ1 or α1 subunit of GABA A receptors and have a reduced adverse event profile. However, no sedative/hypnotics effective against the spectrum of different insomnia complaints are as yet available, and researchers continue to search for compounds that can maintain sleep throughout the night while having an improved safety profile and a rapid onset of action. One nonbenzodiazepine to emerge that shows promise as a ...
Chronic hepatitis B virus (HBV) infection is a major global health concern with an estimated 1-2 ... more Chronic hepatitis B virus (HBV) infection is a major global health concern with an estimated 1-2 million individuals dying every year from hepatitis B-related disease. The goal of treatment for chronic HBV infection is tosuppress HBV replication prior to development of irreversible liver damage which ideally would be accomplished with antiviral agents and immunomodulatory therapy. Over the past 10 years. research has focused on the development of anti-HBV agents able to directly block HBV replication. Naturally occurring nucleoside analogues were used early to treat hepatitis B with little success or high levels of toxicity. The search for novel nucleoside-based chemotherapies continues through modification of the naturally occurring nucleoside-based agents. Of the new generation nucleoside analogues. iamivudine proved to be a potent and well tolerated inhibitor of HBV replication and is clinically available for the treatment of chronic HBV infection. However, long-term treatment wi...
Currently available insulin preparations for the treatment of diabetes mellitus are unable to mim... more Currently available insulin preparations for the treatment of diabetes mellitus are unable to mimic the patterns of endogenous insulin secretion, and normoglycemia cannot be achieved. Inadequate control of hyperglycemia, particularly in patients with type 2 diabetes, is associated with severe microvascular and macrovascular complications. Thus, the search for improved insulin formulations that can reproduce the endogenous insulin secretion profile continues. Considarable advances have been made in the development of noninvasive insulin administration. Significant progress has been achieved in peroral insulin administration that could deliver insulin in a more physiological manner. One such orally active insulin is hexyl insulin monoconjugate 2 (HIM2), a single amphiphilic oligomer covalently linked via an amide bond to the free amino group on the Lys-B29 residue of recombinant human insulin. The alterations in the physicochemical properties of HIM2 as compared to unmodified insulin ...
Arterial hypertension is the most common cardiovascular disease worldwide. Several therapeutic at... more Arterial hypertension is the most common cardiovascular disease worldwide. Several therapeutic atrategies are available for controlling the condition although they mainly target increased diastolic blood pressure. However, it now appears that the increased systolic blood pressure that may be present is an even greater risk. Thus, new strategies for controlling hypertension, and particularly systolic blood pressure, are being developed. One such strategy is dual inhibition of vasopeptidases. These agents suppress activity of both angiotensin-converting enzyme and neprilysin, resulting in increased vasodilating, natriuretic and antiproliferative effects of bradykin, natriuretic peptides and adrenomedullin, which manifests as decreassed vascular tone and reduced blood pressure. MDL-100240 is a dual vasopeptidase inhibitor that has shown potent vasodilating and hypotensive effects and has been chosen for further development as a treatment for hypertension and congestive heart failure.
The emergence of mutidrug-resistant Gram-positive pathogens has created a need for with improved ... more The emergence of mutidrug-resistant Gram-positive pathogens has created a need for with improved efficacy. Researchers have focused on modifying the antibiotic vancomycin and other by adding hydrophobic substituents in order to improve activity, absorption, distribution, metabolism and (TD-6424) is one such novel antibiotic that was found to have multiple mechanisms of action, of bactenal cell wall formation and disruption of cell membrane integrity. The agent showed potent activity against cus aureus and vancomycin-resistant enterococci, among other bacterial species, in vitro and in to two intection models. Telavancin was also shown to have good pharmacokinetics and was effective in phase II clinics trials in patients with Gram-positive skin and soft tissue infections. Phase III clinical trials are in progress.
The standard form of insulin therapy for the treatment of diabetes is via subcutaneous injection.... more The standard form of insulin therapy for the treatment of diabetes is via subcutaneous injection. However, this method of delivery is associated with a reduction in patient compliance and does not mimic the physiological patterns of insulin secretion. As a result, blood glucose and other metabolic parameters cannot be maintained at normal levels. The introduction of rapid- and long-acting insulin analogues has resulted in improved glycemic control, although multiple daily injections are generally required. Alternative routes of insulin delivery have been studied with limited success. Recently, special attention has been given to the pulmonary route of delivery, which has many advantages over other routes and could decrease the number of daily insulin injections, resulting in improved compliance and optimal long-term glycemic control. Of the inhaled insulins under development, the AERx® insulin Diabetes Management System (AERx® iDMS) has shown particular promise. The system involves ...
Osteoporosis is a skeletal disorder characterized by low bone mass and structural deterioration o... more Osteoporosis is a skeletal disorder characterized by low bone mass and structural deterioration of bone tissue leading to bone fragility and an increased risk for fractures. The majority of the agents currently available for the treatment of osteoporosis decrease bone resorption (e.g., estrogens, selective estrogen modulators, calcitonin and bisphosphonates) although some agents increase bone formation (e.g., fluoride and parathyroid hormone). In contrast, strontium ranelate was found to simultaneously decrease bone resorption and stimulate bone formation. It was also shown to increase bone volume and improve the mechanical properties of bone in vivo and was chosen for further development. Strontium ranelate has shown efficacy in preventing early postmenopausal bone loss and reducing the risk of hip fracture in women with postmenopausal osteoporosis. The agent is in phase III development for the prevention and treatment of osteoporosis.
Parkinson's disease is a progressive neurodegenerative disorder for which there is no known c... more Parkinson's disease is a progressive neurodegenerative disorder for which there is no known cure. Agents have been developed to alleviate symptoms, reduce functional disability and slow or arrest progression of the disease, resulting in a near-normal life expectancy and satisfactory quality of life. Dopaminergic agents, which are the mainstay of antiparkinsonian therapy, are effective only during the early phases of the disease and their efficacy is reduced with complications. A novel and promising approach to the treatment of Parkinson's disease is gene therapy, including viral vector-mediated transfer of candidate genes to enhance dopamine production or the survival of dopaminergic neurons. CERE-120 (AAV-hNGF-hNTN) is a novel gene therapy product that delivers a modified human neurturin (NRTN or NTN) gene (i.e., prepro sequence of human neurturin replaced with the prepro domain of human nerve growth factor β [NGFβ]) via an adeno-associated virus type 2 (AAV2) vector under ...
New brief reports this month describe five timely topics: IDO inhibitors have demonstrated antitu... more New brief reports this month describe five timely topics: IDO inhibitors have demonstrated antitumor properties by increasing immune response to tumors and improving chemotherapy effectiveness. One of the current therapeutic efforts for Alzheimer's disease is directed towards blocking the gamma-secretase activity, thus reducing amyloid-beta production. Patients with premature ovarian failure (POF), at present mainly treated with hormone replacement therapy, are belated for novel treatment options. Selective ERbeta agonists are anticipated to emerge as therapeutics for the treatment of various diseases including inflammatory bowel syndrome, endometriosis, dementia and cognitive disorders. Phospholipase A2 inhibitors specific for enzyme isoforms are actively studied as potential antiallergic/antiasthmatic drugs, antiarthritic agents and therapeutics for atherosclerosis.
The discovery of an inducible form of cyclooxygenase (COX) stimulated the search for new, isolom-... more The discovery of an inducible form of cyclooxygenase (COX) stimulated the search for new, isolom-selective inhibitors that culminiated in the introduction of an entirely new generation of antiinfiammatory drugs with improved gestrointestinal tolerability. Cimicoxib (UR-6880), a new imidazole derivative, is a highly selective COX-2 inhibitor that exhibite promising antiinflammatory and analgesic activity. The compound showed good oral activity when tested in experimental models of acute and chronic inflammation and pain, comparable to celecoxib and rotecoxib. Cimicoxib exhibited a good phamacokinetic profile in rats and dogs and a high satety margin as regards both the cardiorespiratory and central nervous systems. In humans, cimicoxib appeared to be safe and well tolerated at doses up to 600 mg. After repeated administration the compound was sale and well tolerated up to 100 mg and there was no significant accumulation after 12 doses. In subjects with moderate to severe postoperativ...
Approximately half of the U.S. adult population suffers from insomnia, with a higher incidence se... more Approximately half of the U.S. adult population suffers from insomnia, with a higher incidence seen in the elderly. The benzodiazepines, sedative/hypnotic drugs which shorten sleep onset latency and increase sleep continuity, have been the standard treatment for insomnia. However, these agents also suppress REM and deep sleep and are associated with unwanted effects such as memory impairment, next-day residual sedation and alteration of hormonal secretion. Another pharmacotherapeutic option for the treatment of insomnia are the nonbenzodlazepines which are seiective for the BZ1 or α1 subunit of GABA A receptors and have a reduced adverse event profile. However, no sedative/hypnotics effective against the spectrum of different insomnia complaints are as yet available, and researchers continue to search for compounds that can maintain sleep throughout the night while having an improved safety profile and a rapid onset of action. One nonbenzodiazepine to emerge that shows promise as a ...
Chronic hepatitis B virus (HBV) infection is a major global health concern with an estimated 1-2 ... more Chronic hepatitis B virus (HBV) infection is a major global health concern with an estimated 1-2 million individuals dying every year from hepatitis B-related disease. The goal of treatment for chronic HBV infection is tosuppress HBV replication prior to development of irreversible liver damage which ideally would be accomplished with antiviral agents and immunomodulatory therapy. Over the past 10 years. research has focused on the development of anti-HBV agents able to directly block HBV replication. Naturally occurring nucleoside analogues were used early to treat hepatitis B with little success or high levels of toxicity. The search for novel nucleoside-based chemotherapies continues through modification of the naturally occurring nucleoside-based agents. Of the new generation nucleoside analogues. iamivudine proved to be a potent and well tolerated inhibitor of HBV replication and is clinically available for the treatment of chronic HBV infection. However, long-term treatment wi...
Currently available insulin preparations for the treatment of diabetes mellitus are unable to mim... more Currently available insulin preparations for the treatment of diabetes mellitus are unable to mimic the patterns of endogenous insulin secretion, and normoglycemia cannot be achieved. Inadequate control of hyperglycemia, particularly in patients with type 2 diabetes, is associated with severe microvascular and macrovascular complications. Thus, the search for improved insulin formulations that can reproduce the endogenous insulin secretion profile continues. Considarable advances have been made in the development of noninvasive insulin administration. Significant progress has been achieved in peroral insulin administration that could deliver insulin in a more physiological manner. One such orally active insulin is hexyl insulin monoconjugate 2 (HIM2), a single amphiphilic oligomer covalently linked via an amide bond to the free amino group on the Lys-B29 residue of recombinant human insulin. The alterations in the physicochemical properties of HIM2 as compared to unmodified insulin ...
Arterial hypertension is the most common cardiovascular disease worldwide. Several therapeutic at... more Arterial hypertension is the most common cardiovascular disease worldwide. Several therapeutic atrategies are available for controlling the condition although they mainly target increased diastolic blood pressure. However, it now appears that the increased systolic blood pressure that may be present is an even greater risk. Thus, new strategies for controlling hypertension, and particularly systolic blood pressure, are being developed. One such strategy is dual inhibition of vasopeptidases. These agents suppress activity of both angiotensin-converting enzyme and neprilysin, resulting in increased vasodilating, natriuretic and antiproliferative effects of bradykin, natriuretic peptides and adrenomedullin, which manifests as decreassed vascular tone and reduced blood pressure. MDL-100240 is a dual vasopeptidase inhibitor that has shown potent vasodilating and hypotensive effects and has been chosen for further development as a treatment for hypertension and congestive heart failure.
The emergence of mutidrug-resistant Gram-positive pathogens has created a need for with improved ... more The emergence of mutidrug-resistant Gram-positive pathogens has created a need for with improved efficacy. Researchers have focused on modifying the antibiotic vancomycin and other by adding hydrophobic substituents in order to improve activity, absorption, distribution, metabolism and (TD-6424) is one such novel antibiotic that was found to have multiple mechanisms of action, of bactenal cell wall formation and disruption of cell membrane integrity. The agent showed potent activity against cus aureus and vancomycin-resistant enterococci, among other bacterial species, in vitro and in to two intection models. Telavancin was also shown to have good pharmacokinetics and was effective in phase II clinics trials in patients with Gram-positive skin and soft tissue infections. Phase III clinical trials are in progress.
The standard form of insulin therapy for the treatment of diabetes is via subcutaneous injection.... more The standard form of insulin therapy for the treatment of diabetes is via subcutaneous injection. However, this method of delivery is associated with a reduction in patient compliance and does not mimic the physiological patterns of insulin secretion. As a result, blood glucose and other metabolic parameters cannot be maintained at normal levels. The introduction of rapid- and long-acting insulin analogues has resulted in improved glycemic control, although multiple daily injections are generally required. Alternative routes of insulin delivery have been studied with limited success. Recently, special attention has been given to the pulmonary route of delivery, which has many advantages over other routes and could decrease the number of daily insulin injections, resulting in improved compliance and optimal long-term glycemic control. Of the inhaled insulins under development, the AERx® insulin Diabetes Management System (AERx® iDMS) has shown particular promise. The system involves ...
Osteoporosis is a skeletal disorder characterized by low bone mass and structural deterioration o... more Osteoporosis is a skeletal disorder characterized by low bone mass and structural deterioration of bone tissue leading to bone fragility and an increased risk for fractures. The majority of the agents currently available for the treatment of osteoporosis decrease bone resorption (e.g., estrogens, selective estrogen modulators, calcitonin and bisphosphonates) although some agents increase bone formation (e.g., fluoride and parathyroid hormone). In contrast, strontium ranelate was found to simultaneously decrease bone resorption and stimulate bone formation. It was also shown to increase bone volume and improve the mechanical properties of bone in vivo and was chosen for further development. Strontium ranelate has shown efficacy in preventing early postmenopausal bone loss and reducing the risk of hip fracture in women with postmenopausal osteoporosis. The agent is in phase III development for the prevention and treatment of osteoporosis.
Parkinson's disease is a progressive neurodegenerative disorder for which there is no known c... more Parkinson's disease is a progressive neurodegenerative disorder for which there is no known cure. Agents have been developed to alleviate symptoms, reduce functional disability and slow or arrest progression of the disease, resulting in a near-normal life expectancy and satisfactory quality of life. Dopaminergic agents, which are the mainstay of antiparkinsonian therapy, are effective only during the early phases of the disease and their efficacy is reduced with complications. A novel and promising approach to the treatment of Parkinson's disease is gene therapy, including viral vector-mediated transfer of candidate genes to enhance dopamine production or the survival of dopaminergic neurons. CERE-120 (AAV-hNGF-hNTN) is a novel gene therapy product that delivers a modified human neurturin (NRTN or NTN) gene (i.e., prepro sequence of human neurturin replaced with the prepro domain of human nerve growth factor β [NGFβ]) via an adeno-associated virus type 2 (AAV2) vector under ...
New brief reports this month describe five timely topics: IDO inhibitors have demonstrated antitu... more New brief reports this month describe five timely topics: IDO inhibitors have demonstrated antitumor properties by increasing immune response to tumors and improving chemotherapy effectiveness. One of the current therapeutic efforts for Alzheimer's disease is directed towards blocking the gamma-secretase activity, thus reducing amyloid-beta production. Patients with premature ovarian failure (POF), at present mainly treated with hormone replacement therapy, are belated for novel treatment options. Selective ERbeta agonists are anticipated to emerge as therapeutics for the treatment of various diseases including inflammatory bowel syndrome, endometriosis, dementia and cognitive disorders. Phospholipase A2 inhibitors specific for enzyme isoforms are actively studied as potential antiallergic/antiasthmatic drugs, antiarthritic agents and therapeutics for atherosclerosis.
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Papers by Lisa A Sorbera