Parkway, CA, United States
Parkway, CA, United States

Time filter

Source Type

News Article | October 28, 2016

When Roger M. Mills, M.D., had the chance to make a late-career change from academic cardiology to the pharmaceutical industry, he had no idea what kind of adventures the next decade would bring. In his new book “Nesiritide: The Rise and Fall of Scios,” Mills gives readers an inside look at the development, early success and subsequent demise of a biotechnology drug that he was personally involved in developing, testing and marketing. “’Nesiritide’ gives the non-medical public an unprecedented insight into the complexity, risk, and competitiveness of drug development,” Mills said. “It demonstrates the devastating impact of media attention to questions of drug safety.” After his time at Scios Inc., the company that developed Nesiritide and after retiring from Janssen Research & Development, LLC as a senior director in clinical research, Mills has adopted the mission of better informing the medical community and the general public about the workings of the often-mysterious pharmaceutical industry. Nesiritide: The Rise and Fall of Scios By Roger M. Mills, M.D. ISBN: 978-1-49179-763-1 Available in softcover, hardcover, e-book Available on Amazon, Barnes & Noble and iUniverse About the author Roger M. Mills, M.D. is a graduate of Amherst College and the University of Pennsylvania medical school. After completing his medical residency, he served in the U.S. Navy before beginning a thirty-year career in academic clinical cardiology as a research fellow at Harvard’s Peter Bent Brigham hospital. He joined Scios Inc., a Johnson & Johnson operating company, in 2005 and later moved to J&J's Janssen Research and Development, LLC. He retired after a 10-year career with J&J, and now lives in Dexter, Mich. with his wife, Katherine, and their Labrador retriever, Posie.

Luedtke G.R.,Scios Inc. | Schinzel K.,Scios Inc. | Tan X.,Scios Inc. | Tester R.W.,Scios Inc. | And 5 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2010

A novel series of N-pyridyl amides as potent p38α kinase inhibitors is described. Based on the structural similarities between the initial hit and a well-known imidazole pyrimidine series of p38α inhibitors, potencies within the newly discovered series were quickly improved by installation of an (S)-α-methylbenzyl moiety at the 2-position of the pyridine ring. The proposed binding modes of the new series to p38α were evaluated against SAR findings and provided rationale for further development of this series of molecules. © 2010 Elsevier Ltd. All rights reserved.

Mavunkel B.J.,Scios Inc. | Perumattam J.J.,Scios Inc. | Tan X.,Scios Inc. | Luedtke G.R.,Scios Inc. | And 10 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2010

The design and synthesis of a new class of p38α MAP kinase inhibitors based on 4-fluorobenzylpiperidine heterocyclic oxalyl amides are described. Many of these compounds showed low-nanomolar activities in p38α enzymatic and cell-based cytokine TNFα production inhibition assays. The optimal linkers between the piperidine and the oxalyl amide were found to be [6,5] fused ring heterocycles. Substituted indoles and azaindoles were favored structural motifs in the cellular assay. © 2009 Elsevier Ltd. All rights reserved.

Medicherla S.,Scios Inc | Ma J.Y.,Scios Inc | Reddy M.,Scios Inc | Esikova I.,Scios Inc | And 4 more authors.
Journal of Inflammation Research | Year: 2010

Certain skin pathologies, including psoriasis, are thought to be immune-mediated inflammatory diseases. Available literature clearly indicates the involvement of inflammatory cells (neutrophils, T cells, and macrophages), their cytokines, and the p38 mitogen-activated protein kinase (MAPK) signaling pathway in the pathophysiology of psoriasis. Neutrophils play an important role in the formation of acute inflammatory changes in psoriasis. Acute inflammation or acute flares in psoriasis remain poorly addressed in clinical medicine. In this communication, we first establish a simple and reproducible model for studying neutrophil-mediated acute skin inflammation. Using the hairless guinea pig, due to the similarity of skin architecture to that of human, acute inflammation was induced with an intradermal injection of 50 μg/mL lipopolysaccharide (LPS) in 50 μL solution. Myeloperoxidase (MPO) activity was measured by MPO-positive neutrophils and shown to increase for 24-hours post-injection. Simultaneously, the level of phosphorylated p38 MAPK was documented for 48-hours post-LPS injection in the skin. Next, we used this model to examine the therapeutic potential of an α-selective p38 MAPK inhibitor, SCIO-469. A comparison of topical application of SCIO-469 at 5 mg/mL or 15 mg/mL to vehicle revealed that SCIO-469 dose-dependently reduces acute skin inflammation and that this effect is statistically significant at the higher dose. Further examination of tissues that received this dose also revealed statistically significant reduction of MPO activity, phosphorylated p38 MAPK, interleukin-6, and cyclooxygenase-2. These data suggest that the α-selective p38 MAPK inhibitor, SCIO-469, acts as a topical anti-inflammatory agent via the p38 MAPK pathway to reduce neutrophil induced acute inflammation in the skin. These observations suggest that α-selective p38 MAPK inhibition may be an effective therapeutic strategy to manage acute skin inflammation. © 2010 Medicherla et al, publisher and licensee Dove Medical Press Ltd.

Scios Inc. | Date: 2011-03-09

The invention relates to an in vitro method of diagnosing congestive heart disease by quantifying hBNP in a sample. The method comprises: contacting a sample of the biological fluid with a first antibody, wherein the first antibody is monospecifically reactive to an hBNP fragment; forming a complex comprising hBNP in the biological fluid, the first antibody and a second antibody, wherein the second antibody is immunoreactive with hBNP or the first antibody, and wherein the second antibody comprises a label; and determining the amount of hBNP in the sample by quantifying the label in the complex.

Scios Inc. | Date: 2011-08-24

The present invention is based on the findings that BACE2, a homolog of -secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of A. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE2 to suppress A production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimers disease and other neurological diseases.

A method is described for producing a peptide having a pI above 8 or below 5 wherein the peptide is expressed as a fusion protein in which it is linked to a fusion partner through an acid cleavage site. The peptide is released from the fusion partner by acid cleavage in the absence of chaotrope. The fusion partner and its acid cleavage products, if any, have a net charge sufficiently different from that of the desired peptide to allow isolation of the peptide by ion-exchange chromatography.

p38 Mitogen-activated protein kinase (MAPK) plays a critical role in the activation of inflammatory cells. We investigated the anti-inflammatory effects of a p38-selective MAPK inhibitor (SD-282) in a mouse transgenic (CC10:IL-13) asthma model. The CC-10-driven over-expression of IL-13 in the mouse lung/airway has been shown to result in a remarkable phenotype recatitulating many features of asthma and characterized by eosinophilic and mononuclear inflammation, with airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of Charcot-Leyden-like crystal, and airway sub-epitheilial fibrosis. Here we show how activated p38 MAPK can be observed in the lungs at the onset of asthma ie, around 8 weeks of age in both female and male mice. We also show that administration of a p38 MAPK selective inhibitor, SD-282 at 30 or 90 mg/kg, twice a day for a period of four weeks beginning at the onset of asthma, significantly reduced the inflammation (p < 0.001); hyperplasia of airway epithelium (p < 0.05); goblet cell metaplasia and mucus hypersecretion (p < 0.001) and reduced lung remodeling and fibrosis (p < 0.01), alleviating the severity of lung damage as measured by a composite score (p < 0.05). Furthermore, SD-282 significantly reduced activated p38 MAPK in the lymphocytes and epithelial cells (p < 0.001). Simultaneously, identical studies were conducted with an anti-fibrotic TGFR1 kinase inhibitor (SD-208) which demonstrated anti-fibrotic but not anti-inflammatory properties. These findings suggest that the p38-selective MAPK inhibitor may have dual therapeutic potential in attenuating both the inflammatory component and the fibrotic component of asthma and other Th2-polarized inflammatory lung diseases.

PubMed | Scios Inc.
Type: | Journal: Diabetes, metabolic syndrome and obesity : targets and therapy | Year: 2011

In healthy tissue, a wound initiates an inflammatory response characterized by the presence of a hematoma, infiltration of inflammatory cells into the wound and, eventually, wound healing. In pathological conditions like diabetes mellitus, wound healing is impaired by the presence of chronic nonresolving inflammation. p38 mitogen-activated protein kinase (MAPK) inhibitors have demonstrated anti-inflammatory effects, primarily by inhibiting the expression of inflammatory cytokines and regulating cellular traffic into wounds. The db/db mouse model of type 2 diabetes was used to characterize the time course of expression of activated p38 during impaired wound healing. The p38-selective inhibitor, SCIO-469, was applied topically and effects on p38 activation and on wound healing were evaluated. A topical dressing used clinically, Promogran, was used as a comparator. In this study, we established that p38 is phosphorylated on Days 1 to 7 post-wounding in db/db mice. Further, we demonstrated that SCIO-469, at a dose of 10 g/wound, had a positive effect on wound contraction, granulation tissue formation, and re-epithelialization, and also increased wound maturity during healing. These effects were similar to or greater than those observed with Promogran. These results suggest a novel approach to prophylactic and therapeutic management of chronic wounds associated with diabetes or other conditions in which healing is impaired.

PubMed | Scios Inc
Type: | Journal: Methods in molecular medicine | Year: 2011

The accumulation of insoluble A peptide aggregates in the brain is the diagnostic feature of Alzheimers disease. Identical deposits are seen in the elderly who are at risk for this disease. The formation of the approx 4 kDa A peptide is implicated as a key component in the development of Alzheimers disease pathology. Genetic evidence strongly supports this contention (1,2), as well as a number of demonstrated relevant biological activities of the A peptide such as its neurotoxicity (3) and proinflammatory properties (4). A great deal of attention has been focused on the processes involved in the generation of A peptide. In contrast, the fate of this peptide once it has been released from the cell is less well understood. Recently, this situation has been changing as studies on the clearance of A peptide are being published. The identification of A-degrading enzymes produced in the brain, their class, and selectivity, as well as their cellular origin, are important unresolved questions. One key issue of A peptide clearance is whether the brain may be limited in its capacity to degrade this protein, as all cells produce A, yet it is seen to accumulate only in brain tissue. Because alterations in A peptide clearance may potentially contribute to increased levels and to the development of insoluble A deposits in the brains of afflicted individuals, this chapter focuses on specific approaches to clarifying A peptide-clearance mechanisms.

Loading Scios Inc. collaborators
Loading Scios Inc. collaborators