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项与 Psychiatric Genomics, Inc. 相关的药物

PGX-200097

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COMT x D2 receptor

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COMT抑制剂 [+1]

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原研机构

Psychiatric Genomics, Inc.

在研适应症-

非在研适应症

精神分裂症

最高研发阶段终止

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PGX-5188

靶点-

作用机制-

在研机构-

原研机构

Psychiatric Genomics, Inc.

在研适应症-

非在研适应症

躁郁症

最高研发阶段终止

首次获批国家/地区-

首次获批日期-

100 项与 Psychiatric Genomics, Inc. 相关的临床结果

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0 项与 Psychiatric Genomics, Inc. 相关的专利（医药）

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5

项与 Psychiatric Genomics, Inc. 相关的文献（医药）

2004-03-17·The Journal of Neuroscience1区 · 医学

Electroconvulsive Seizures Regulate Gene Expression of Distinct Neurotrophic Signaling Pathways

1区 · 医学

Article

作者: Laeng, Pascal ; Young, Theresa A. ; Jurata, Linda W. ; Brockman, Jeffrey A. ; Bukhman, Yury V. ; Palfreyman, Michael G. ; Altar, C. Anthony ; Bullard, Jeffrey ; Charles, Vinod ; Lemire, Andrew

Electroconvulsive therapy (ECT) remains the treatment of choice for drug-resistant patients with depressive disorders, yet the mechanism for its efficacy remains unknown. Gene transcription changes were measured in the frontal cortex and hippocampus of rats subjected to sham seizures or to 1 or 10 electroconvulsive seizures (ECS), a model of ECT. Among the 3500–4400 RNA sequences detected in each sample, ECS increased by 1.5- to 11-fold or decreased by at least 34% the expression of 120 unique genes. The hippocampus produced more than three times the number of gene changes seen in the cortex, and many hippocampal gene changes persisted with chronic ECS, unlike in the cortex. Among the 120 genes, 77 have not been reported in previous studies of ECS or seizure responses, and 39 were confirmed among 59 studied by quantitative real time PCR. Another 19 genes, 10 previously unreported, changed by <1.5-fold but with very high significance. Multiple genes were identified within distinct pathways, including the BDNF–MAP kinase–cAMP–cAMP response element-binding protein pathway (15 genes), the arachidonic acid pathway (5 genes), and more than 10 genes in each of the immediate-early gene, neurogenesis, and exercise response gene groups. Neurogenesis, neurite outgrowth, and neuronal plasticity associated with BDNF, glutamate, and cAMP–protein kinase A signaling pathways may mediate the antidepressant effects of ECT in humans. These genes, and others that increase only with chronic ECS such as neuropeptide Y and thyrotropin-releasing hormone, may provide novel ways to select drugs for the treatment of depression and mimic the rapid effectiveness of ECT.

2003-06-01·Journal of Biological Chemistry2区 · 生物学

Peroxisome Proliferator-activated Receptor γ-mediated Differentiation

2区 · 生物学

Article

作者: Charis Eng ; Elisabetta Mueller ; Pasha Sarraf ; Rajnish A. Gupta ; Jeffery J. Prusakiewicz ; Raymond N. DuBois ; Jeffrey A. Brockman ; Timothy M. Willson

Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) inhibits cell growth and induces differentiation in both adipocyte and epithelial cell lineages, although it is unclear whether this occurs through common or cell-type specific mechanisms. We have identified four human colon cancer cell lines that do no undergo growth inhibition or induce markers of differentiation after exposure to PPARgamma agonists. Sequence analysis of the PPARgamma gene revealed that all four cell lines contain a previously unidentified point mutation in the ninth alpha-helix of the ligand binding domain at codon 422 (K422Q). The mutant receptor did not exhibit any defects in DNA binding or retinoid X receptor heterodimerization and was transcriptionally active in an artificial reporter assay. However, only retroviral transduction of the wild-type (WT), but not mutant, receptor could restore PPARgamma ligand-induced growth inhibition and differentiation in resistant colon cancer cell lines. In contrast, there was no difference in the ability of fibroblast cells expressing WT or K422Q mutant receptor to undergo growth inhibition, express adipocyte differentiation markers, or uptake lipid after treatment with a PPARgamma agonist. Finally, analysis of direct PPARgamma target genes in colon cancer cells expressing the WT or K422Q mutant allele suggests that the mutation may disrupt the ability of PPARgamma to repress the basal expression of a subset of genes in the absence of exogenous ligand. Collectively, these data argue that codon 422 may be a part of a co-factor(s) interaction domain necessary for PPARgamma to induce terminal differentiation in epithelial, but not adipocyte, cell lineages and argues that the receptor induces growth inhibition and differentiation via cell lineage-specific mechanisms.

2003-01-01·Journal of Analytical Methods in Chemistry

Managing smaller but flexible automation: back to the future

Article

作者: Drabik, Christopher ; Evans, David M ; Russo, Joseph ; Hook, Derek J ; Hook, Derek J. ; Deiparine, Mark ; Evans, David M.

Practical robotics tools were introduced to the analytical chemistry laboratory about 20 years ago with the development of the Zymate I robot by Zymark Corporation (Hopkington, MA, USA). These tools quickly migrated within the various parts of the research divisions into biology and biochemistry laboratories at pharmaceutical companies to support the new discipline of high-throughput random screening. These systems were small scale and often reconfigured for new screens because of small numbers of compounds in collections at that time. Over the last 10 years, however, these systems have matured, and it became clear that laboratory automation was becoming a reliable tool for drug discovery. Over this period, management in the pharmaceutical research industry was convinced that this technology and approach was a productivity enhancing tool and invested heavily in infrastructure and people to implement it. During this time, three other trends contributed to the momentum towards large dedicated ‘industrialized’ screening operations. One was the proliferation of molecular targets that were being produced by the genomics revolution; the second the move towards detection technologies that were either homogeneous or semihomogeneous eliminating many of the separation steps in assays; and the third the development of large combinatorial chemistry/parallel synthesis capability in the research organizations, often linked to very largescale compound collections and compound management systems.

100 项与 Psychiatric Genomics, Inc. 相关的药物交易

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100 项与 Psychiatric Genomics, Inc. 相关的转化医学

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