Thursday, January 17, 2013

SciBX: Science-Business eXchange Contents: January 17 2013, Volume 6 / Issue 2

SciBX: Science-Business eXchange

TABLE OF CONTENTS

January 17 2013, Volume 6 / Issue 2

Analysis

Cover Story
Targets and Mechanisms

The Distillery: Therapeutics

Cancer
Infectious disease
Musculoskeletal disease
Neurology
Other

The Distillery: Techniques

Assays and screens
Chemistry
Computational models
Drug delivery
Drug platforms
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Analysis

Cover Story

Top

HER2's new mutations
Tim Fulmer
doi:10.1038/scibx.2013.26
Washington University in St. Louis School of Medicine researchers have used next-generation sequencing to identify mutations in HER2 that are missed by standard screening tests. Based on the findings, the researchers are now recruiting patients with breast cancer expressing the mutations for a Phase II trial of Puma's HER2-targeting compound, neratinib.
Full Text | PDF

Targets and Mechanisms

Top

Overcoming amantadine resistance
Lauren Martz
doi:10.1038/scibx.2013.27
A group of U.S. researchers has developed inhibitors of the influenza A virus M2 mutant that is responsible for most resistance to amantadine. InfluMedix has licensed the compounds and expects to bring a new influenza antiviral to the market within five years.
Full Text | PDF

What to do with PKM2
Tracey Baas
doi:10.1038/scibx.2013.28
Novartis has shown that the absence of pyruvate kinase M2 isozyme has no effect on cancer cell proliferation in mice, thus suggesting PKM2 inhibition alone might not be an effective strategy to stop tumor growth. Biotechs working on PKM2 modulators think it is too early to write off the target.
Full Text | PDF

γ-Secretase lost and sound
Lev Osherovich
doi:10.1038/scibx.2013.29
Japanese and U.S. researchers have shown that inhibiting γ-secretase in the middle ear can promote hair cell regeneration and recovery from deafness in rodents. Keeping potentially toxic γ-secretase inhibitors confined to the ear will require formulation and delivery innovations.
Full Text | PDF

Distillery: Therapeutics

Cancer

Top

Mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1)
doi:10.1038/scibx.2013.30
In vitro and mouse studies identified small molecule MALT1 inhibitors that could help treat patients with the activated B cell (ABC) subtype of diffuse large B cell lymphoma (DLBCL).
Full Text | PDF

Inhibitor of DNA binding 1 (ID1)
doi:10.1038/scibx.2013.31
Patient sample, mouse and cell culture studies suggest inhibiting ID1 could help treat glioblastoma.
Full Text | PDF

Phosphoinositide 3-kinase (PI3K); mammalian target of rapamycin (mTOR; FRAP; RAFT1); Janus kinase-2 (JAK-2)
doi:10.1038/scibx.2013.32
In vitro and mouse studies suggest JAK-2 inhibitors could help increase the efficacy of PI3K and mTOR inhibitors against triple-negative breast cancer.
Full Text | PDF

p53
doi:10.1038/scibx.2013.33
Cell culture and mouse studies suggest reducing dietary serine could help treat p53-deficient cancers.
Full Text | PDF

Epidermal growth factor receptor (EGFR)
doi:10.1038/scibx.2013.34
A high throughput screening study suggests the staurosporine-based research compound Gö6967 could aid the development of new treatments for NSCLCs with resistance mutations in EGFR.
Full Text | PDF

Infectious disease

Top

Undecaprenyl diphosphate synthase (uppS)
doi:10.1038/scibx.2013.35
In vitro and mouse studies identified inhibitors of uppS that could help treat bacterial infection.
Full Text | PDF

Platelet factor 4 (PF4; CXCL4)
doi:10.1038/scibx.2013.36
In vitro and mouse studies suggest small molecule mimetics of PF4 could help treat malaria.
Full Text | PDF

Leukocyte cell-derived chemotaxin 2 (LECT2)
doi:10.1038/scibx.2013.37
In vitro and mouse studies suggest LECT2 could help treat sepsis.
Full Text | PDF

Musculoskeletal disease

Top

Peroxisome proliferation–activated receptor-γ coactivator 1α isoform 4 (PPARGC1A4; PGC-1α4)
doi:10.1038/scibx.2013.38
Mouse studies suggest upregulating PGC-1α4 could help increase muscle mass.
Full Text | PDF

Neurology

Top

Dopamine D2 receptor
doi:10.1038/scibx.2013.39
In vitro and mouse studies suggest dopamine D2 receptor agonists could help treat neuroinflammation in diseases such as PD.
Full Text | PDF

Other

Top

γ-Secretase; notch 1 (NOTCH1)
doi:10.1038/scibx.2013.40
Studies in cell culture and in rodents suggest blocking NOTCH1 processing using g-secretase inhibitors could help treat hearing loss.
Full Text | PDF

Distillery: Techniques

Assays and screens

Top

High throughput combinatorial screening to identify genotype-selective combination therapies for melanoma
doi:10.1038/scibx.2013.41
High throughput combinatorial screening could be useful for identifying genotype-selective combination therapies to treat melanoma.
Full Text | PDF

Chemistry

Top

Hydrolysis-resistant proteins with Pictet-Spengler ligations
doi:10.1038/scibx.2013.42
Pictet-Spengler ligations could be useful for creating hydrolysis-resistant biologics.
Full Text | PDF

Computational models

Top

Computational algorithm for designing G protein–coupled receptor (GPCR) ligands against a predefined set of targets
doi:10.1038/scibx.2013.43
A computational algorithm could be used to design GPCR ligands that modulate a predefined set of targets.
Full Text | PDF

Drug delivery

Top

pH (low) insertion peptides (pHLIPs) for drug delivery to ischemic myocardium
doi:10.1038/scibx.2013.44
pHLIPs could be useful for delivering imaging agents or therapeutics to ischemic regions of the heart that have lower pH values than nonischemic regions.
Full Text | PDF

pH (low) insertion peptides (pHLIPs) for delivery of gold nanoparticles to tumors
doi:10.1038/scibx.2013.45
pHLIPs could be used to target gold nanoparticles to tumors, which tend to have lower pH than normal tissue.
Full Text | PDF

Drug platforms

Top

Chimeric antigen receptors (CARs) that require dual-antigen binding for activation
doi:10.1038/scibx.2013.46
T cells engineered to express a CAR and a chimeric co-stimulatory receptor could enhance the tumor specificity of targeted T cell therapies.
Full Text | PDF

Direct conversion of quiescent cardiomyocytes into pacemaker cells
doi:10.1038/scibx.2013.47
A gene therapy approach for direct conversion of quiescent cardiomyocytes into pacemaker cells could be useful for treating arrhythmias.
Full Text | PDF

Production of antibody-toxin fusion immunotoxins in algae
doi:10.1038/scibx.2013.48
In vitro and mouse studies suggest algae chloroplasts could be used to produce anticancer immunotoxin fusion proteins.
Full Text | PDF

Targeting ventral tegmental area (VTA) dopaminergic neurons to treat depression
doi:10.1038/scibx.2013.49
Targeting a subset of dopaminergic neurons could be useful for reducing depression-related behaviors.
Full Text | PDF

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