Thursday, March 29, 2012

SciBX: Science-Business eXchange Contents: March 29 2012, Volume 5 / Issue 13

SciBX: Science-Business eXchange

TABLE OF CONTENTS

March 29 2012, Volume 5 / Issue 13

Analysis

Cover Story
Targets and Mechanisms
Public-Private Interface

The Distillery: Therapeutics

Autoimmune disease
Cancer
Cardiovascular disease
Dermatology
Endocrine/metabolic disease
Gastrointestinal disease
Musculoskeletal disease
Neurology
Transplantation

The Distillery: Techniques

Chemistry
Drug platforms
Markers
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Analysis

Cover Story

Top

Memory is skin deep
Tracey Baas
doi:10.1038/scibx.2012.322
A Harvard Medical School team has identified a T cell–based immune response in the skin that is better at protecting mice from some viral infections than circulating T cells. Trem Rx is developing a vaccine platform against infectious diseases and cancer based on these results.
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Targets and Mechanisms

Top

PARP target practice
Joanne Kotz
doi:10.1038/scibx.2012.323
Swedish researchers have used an in vitro screen to evaluate the target selectivity of a panel of small molecule PARP inhibitors. The findings could eventually lead to next-generation PARP inhibitors that have a better therapeutic index than inhibitors currently in the cancer clinic.
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Sugar free
Lev Osherovich
doi:10.1038/scibx.2012.324
An international team has indirect genetic evidence that inhibiting the C isoform of ketohexokinase can block weight gain and insulin in a mouse model of metabolic syndrome. The challenge now is to selectively inhibit the disease-associated form of the enzyme without compromising systemic sugar metabolism.
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Public-Private Interface

Top

IMI's leadoff hitter
Kai-Jye Lou
doi:10.1038/scibx.2012.325
Europe's Innovative Medicines Initiative has recruited 7 pharmas to each contribute up to 50,000 compounds from their proprietary libraries for a public-private partnership called the European Lead Factory. The pharmas will have access to an expanded chemical space, and academic members of the factory will be able to run experiments with high-quality molecules.
Full Text | PDF

Distillery: Therapeutics

Autoimmune disease

Top

Protein tyrosine phosphatase non-receptor type 22 (PTPN22; LYP)
doi:10.1038/scibx.2012.326
In vitro studies identified a LYP inhibitor that could help treat autoimmune diseases.
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Cancer

Top

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)
doi:10.1038/scibx.2012.327
Mouse studies suggest TRAIL could eliminate cancer stem cells to help treat ALL.
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VEGF receptor 2 (KDR/Flk-1; VEGFR-2)
doi:10.1038/scibx.2012.328
In vitro and mouse studies suggest inhibiting VEGFR-2 could help treat glioblastoma multiforme (GBM).
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Euchromatic histone-lysine N-methyltransferase 2 (EHMT2; G9A); DNA methyltransferase
doi:10.1038/scibx.2012.329
Cell culture and mouse studies suggest blocking both G9A histone methyltransferase activity and its interactions with DNA methyltransferases could help treat breast cancer.
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Cytoplasmic dynein
doi:10.1038/scibx.2012.330
In vitro and cell culture studies identified small molecule inhibitors of cytoplasmic dynein that could help treat cancer.
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Interferon-β (IFNB; IFN-β)
doi:10.1038/scibx.2012.331
Mouse studies suggest a synthetic sialyl-IFNB compound could help treat cancer.
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Not applicable
doi:10.1038/scibx.2012.332
In vitro and mouse studies identified an isomer of 2-(4-methoxyphenyl)-4-quinolinyl) 2-piperidinyl-methanol that could help treat multidrug-resistant (MDR) cancers.
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Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1; RAC1)
doi:10.1038/scibx.2012.333
In vitro studies identified a RAC1 inhibitor that could help treat metastatic cancers.
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Epstein-Barr nuclear antigen 3B (EBNA3B)
doi:10.1038/scibx.2012.334
Mouse and patient sample studies suggest increasing EBNA3B signaling could help prevent Epstein-Barr virus (EBV)-associated lymphoma.
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Leukotriene B4 type 2 receptor (BLT2)
doi:10.1038/scibx.2012.335
In vitro and mouse studies suggest inhibiting BLT2 could help reduce ovarian cancer metastasis.
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Cardiovascular disease

Top

Potassium channel Kv1.5 (KCNA5)
doi:10.1038/scibx.2012.336
In vitro and in vivo studies suggest a new class of KCNA5 inhibitors could help treat atrial fibrillation (AF).
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Dermatology

Top

Cysteinyl leukotriene receptor 2 (CYSLTR2; CysLT2); leukotriene C4 synthase (LTC4S)
doi:10.1038/scibx.2012.337
Mouse studies suggest inhibiting leukotriene C4 signaling through LTC4S and CysLT2 could help treat atopic dermatitis.
Full Text | PDF

Endocrine/metabolic disease

Top

Sphingosine-1-phosophate phosphatase 1 (SGPP1)
doi:10.1038/scibx.2012.338
Cell culture studies suggest antagonizing SGPP1 could help treat type 2 diabetes.
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Ketohexokinase (fructokinase; KHK)
doi:10.1038/scibx.2012.339
Mouse studies suggest antagonizing the C isoform of KHK could help treat metabolic syndrome and obesity.
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Phosphoinositide 3-kinase (PI3K); PI3Kα; PI3Kδ; PTEN (MMAC1; TEP1)
doi:10.1038/scibx.2012.340
Mouse studies suggest inhibiting PI3K could help treat obesity.
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Gastrointestinal disease

Top

Leucine-rich repeat-containing G protein–coupled receptor 5 (LGR5; GPR49)
doi:10.1038/scibx.2012.341
Cell culture and mouse studies suggest engraftment of stem cell–derived colon tissues could help treat colitis and other gastrointestinal epithelial injuries.
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Musculoskeletal disease

Top

Not applicable
doi:10.1038/scibx.2012.342
In vitro and mouse studies suggest betulinic acid analogs could help treat osteoporosis.
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Neurology

Top

Cannabinoid CB2 receptor (CNR2)
doi:10.1038/scibx.2012.343
Tissue, cell culture and mouse studies suggest agonizing CNR2 could help treat brain inflammation.
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Not applicable
doi:10.1038/scibx.2012.344
Mouse studies suggest bone marrow transplantation and enhancing microglial activity could both help treat Rett syndrome, a form of autism caused by a mutation in methyl CpG binding protein 2 (MECP2; RTT).
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Hydrogen voltage-gated channel 1 (HVCN1)
doi:10.1038/scibx.2012.345
Studies in cell culture and in mice suggest antagonizing HVCN1 could help prevent brain damage caused by ischemic stroke.
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Prokineticin 2 (PROK2; Bv8); prokineticin receptor 2 (PROKR2; PKR2)
doi:10.1038/scibx.2012.346
Rat studies suggest inhibiting PROK2 signaling could help treat stroke.
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Transplantation

Top

MicroRNA-155 (miR-155)
doi:10.1038/scibx.2012.347
Mouse studies suggest inhibiting miR-155 could help treat acute GvHD.
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Distillery: Techniques

Chemistry

Top

Ring expansion approach for synthesizing libraries of macrolactones and macrolactams
doi:10.1038/scibx.2012.348
A synthetic approach using ring expansion to generate lactone and lactam classes of macrocycles could provide new drug leads for targets that are difficult to modulate with small molecules.
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Drug platforms

Top

Ester and esterase chemistry for tissue-specific drug activation and imaging
doi:10.1038/scibx.2012.349
In vitro and cell culture studies suggest engineered esterases could be used to selectively activate dyes and prodrugs for tissue-specific imaging and drug delivery.
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Markers

Top

Truncating mutations in titin (TTN) as a marker of dilated cardiomyopathy
doi:10.1038/scibx.2012.350
Screening for truncating mutations in TTN could help diagnose dilated cardiomyopathy, a weakening of the cardiac muscle that can lead to congestive heart failure.
Full Text | PDF

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