Thursday, August 9, 2012

SciBX: Science-Business eXchange Contents: August 9 2012, Volume 5 / Issue 31

SciBX: Science-Business eXchange

TABLE OF CONTENTS

August 9 2012, Volume 5 / Issue 31

Analysis

Cover Story
Targets and Mechanisms

The Distillery: Therapeutics

Autoimmune disease
Cancer
Cardiovascular disease
Endocrine/metabolic disease
Infectious disease
Inflammation
Neurology
Ophthalmic disease
Other
Various

The Distillery: Techniques

Assays and screens
Drug delivery
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Analysis

Cover Story

Top

Hitting histone demethylases
Joanne Kotz
doi:10.1038/scibx.2012.805
A GSK–Structural Genomics Consortium team has identified the first potent and selective histone demethylase inhibitor and shown that the molecule dampens the macrophage inflammatory response. The pharma now is focusing on internal efforts and external approaches to exploring potential therapeutic applications of the inhibitor.
Full Text | PDF

Targets and Mechanisms

Top

Isis takes on myotonic dystrophy
Lev Osherovich
doi:10.1038/scibx.2012.806
Researchers at the University of Rochester and Isis have come up with an efficient way to treat symptoms of myotonic dystrophy type 1 in mice using systemically delivered antisense oligonucleotides. The finding has fueled an early stage development deal between Isis and Biogen.
Full Text | PDF

CXCR2 antagonists in breast cancer
Lauren Martz
doi:10.1038/scibx.2012.807
A Memorial Sloan-Kettering Cancer Center team has shown that CXC chemokine receptor 2 antagonists sensitized tumors to chemotherapy in mice with metastatic breast cancer. The team is working on additional preclinical studies with the intention of moving the antagonists into clinical trials for breast cancer.
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Screening for immunogenic cell death
Kai-Jye Lou
doi:10.1038/scibx.2012.808
French researchers have used a fluorescence-based screening platform to identify small molecules that induced immunogenic cell death in mouse tumors. Next, the group plans to test the best hits in a Phase I/II trial to treat locally invasive head and neck cancers in combination with chemotherapy.
Full Text | PDF

Distillery: Therapeutics

Autoimmune disease

Top

Jumonji domain containing 3 (JMJD3; KDM6B); lysine-specific demethylase 6A (KDM6A; UTX)
doi:10.1038/scibx.2012.809
An in vitro and cell culture study identified a compound that inhibited the histone demethylases JMJD3 and UTX and that could help treat autoimmune diseases.
Full Text | PDF

Cancer

Top

Chemokine CXC motif ligand 1 (CXCL1; GRO; MGSA); CXCL2 (MIP2); CXC chemokine receptor 2 (CXCR2; IL8RB)
doi:10.1038/scibx.2012.810
In vitro and mouse studies suggest antagonizing CXCR2 could prevent resistance to chemotherapy and metastasis in breast cancer.
Full Text | PDF

BRAF; MEK
doi:10.1038/scibx.2012.811
In vitro studies suggest MEK inhibitors could help treat melanomas carrying the BRAF L597 mutation.
Full Text | PDF

Mdm4 p53 binding protein homolog (MDM4; MDMX)
doi:10.1038/scibx.2012.812
Mouse and cell culture studies suggest antagonizing MDM4 could help treat melanoma.
Full Text | PDF

Cardiovascular disease

Top

Mammalian target of rapamycin complex 1 (mTORC1); lamin A/C (LMNA)
doi:10.1038/scibx.2012.813
In vitro and mouse studies suggest inhibiting mTORC1 could help treat laminopathies including dilated cardiomyopathy.
Full Text | PDF

Endocrine/metabolic disease

Top

Free fatty acid receptor 1 (FFAR1; GPR40)
doi:10.1038/scibx.2012.814
Mouse and in vitro studies have identified GPR40 agonists that could help treat type 2 diabetes.
Full Text | PDF

Pyroglutamylated RFamide peptide receptor (QRFPR; GPR103)
doi:10.1038/scibx.2012.815
Mouse and in vitro studies suggest a GPR103 agonist could increase food intake to help treat anorexia.
Full Text | PDF

Infectious disease

Top

Phospholipase A2 group IVA cytosolic calcium-dependent (PLA2G4A; cPLA2-α)
doi:10.1038/scibx.2012.816
In vitro studies suggest inhibiting PLA2G4A could help treat HCV infection and dengue fever.
Full Text | PDF

Glucose-6-phosphate dehydrogenase (g6pd)
doi:10.1038/scibx.2012.817
In vitro studies identified Plasmodium falciparum g6pd inhibitors that could help treat malaria.
Full Text | PDF

Inflammation

Top

APAF1 interacting protein (APIP)
doi:10.1038/scibx.2012.818
In vitro and genetic sequencing studies suggest reducing APIP expression could help treat systemic inflammatory response syndrome (SIRS), which is a whole-body inflammatory state that can occur in response to infection.
Full Text | PDF

Neurology

Top

β-Site APP-cleaving enzyme 1 (BACE1); amyloid precursor protein (APP)
doi:10.1038/scibx.2012.819
Human genetic, cell culture and in vitro assay studies suggest the A673T substitution in APP may protect against AD and normal cognitive decline.
Full Text | PDF

NMDAR
doi:10.1038/scibx.2012.820
In vitro and mouse studies have identified a hydrogen sulfide (H2S)-releasing NMDAR antagonist that could help treat stroke.
Full Text | PDF

Ophthalmic disease

Top

Nicotinamide nucleotide adenylyltransferase 1 (NMNAT1)
doi:10.1038/scibx.2012.821
Studies with human tissues identified multiple NMNAT1 mutations that could help diagnose Leber's congenital amaurosis (LCA).
Full Text | PDF

Unknown
doi:10.1038/scibx.2012.822
Mouse studies suggest a photosensitive compound could help treat retinitis pigmentosa (RP).
Full Text | PDF

Other

Top

Cytochrome P450 family 11 subfamily B polypeptide 1 (CYP11B1)
doi:10.1038/scibx.2012.823
In vitro studies identified CYP11B1 inhibitors that could help treat Cushing's disease.
Full Text | PDF

Various

Top

Not applicable
doi:10.1038/scibx.2012.824
In vitro and mouse studies suggest preventing formation of neutrophil extracellular traps (NETs) could help prevent thrombosis in patients with cancer.
Full Text | PDF

Distillery: Techniques

Assays and screens

Top

Impact of receptor tyrosine kinase (RTK) ligands on sensitivity of human tumor–derived cell lines to kinase inhibitors
doi:10.1038/scibx.2012.825
Analysis of the impact of RTK ligands on sensitivity of human tumor–derived cell lines to kinase inhibitors could guide combination therapy to prevent drug resistance.
Full Text | PDF

Stromal and cancer cell coculture system to uncover drug resistance mechanisms and guide combination therapy
doi:10.1038/scibx.2012.826
A stromal and cancer cell coculture system could help uncover drug resistance mechanisms and guide combination therapy.
Full Text | PDF

Drug delivery

Top

Intracellular delivery of therapeutic small interfering RNA with carbonate co-oligomers
doi:10.1038/scibx.2012.827
Carbonate co-oligomers for intracellular delivery of therapeutic siRNA could help treat a range of diseases.
Full Text | PDF

Nanoparticle vaccines targeted to the large intestine
doi:10.1038/scibx.2012.828
Nanoparticle vaccines targeted to the large intestine could help protect against mucosal infections.
Full Text | PDF

Systemic delivery of antisense oligonucleotide therapy for myotonic dystrophy type 1 (DM1)
doi:10.1038/scibx.2012.829
A study in mice suggests subcutaneous injection of an antisense oligonucleotide could help treat DM1.
Full Text | PDF

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