Thursday, May 24, 2012

SciBX: Science-Business eXchange Contents: May 24 2012, Volume 5 / Issue 21

SciBX: Science-Business eXchange

TABLE OF CONTENTS

May 24 2012, Volume 5 / Issue 21

Analysis

Cover Story
Targets and Mechanisms

The Distillery: Therapeutics

Cancer
Cardiovascular disease
Endocrine/metabolic disease
Musculoskeletal disease
Neurology

The Distillery: Techniques

Assays and screens
Chemistry
Drug platforms
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Analysis

Cover Story

Top

Reviving Ras
Joanne Kotz
doi:10.1038/scibx.2012.536
Genentech and Vanderbilt teams have independently used fragment-based drug discovery to identify a new small molecule binding site that blocks activation of Ras, a highly prevalent oncoprotein that has previously been considered undruggable. The results could reinvigorate drug discovery efforts against the target.
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Targets and Mechanisms

Top

Cooling down AD
Lev Osherovich
doi:10.1038/scibx.2012.537
A Johns Hopkins University team has clinical proof-of-concept data for slowing the progression of Alzheimer's disease by reducing activity in the hippocampus with antiepileptic drugs. AgeneBio has licensed the IP and is planning a Phase II trial of an antiepileptic to prevent AD.
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Getting around peripartum cardiomyopathy
Michael J. Haas
doi:10.1038/scibx.2012.538
A Harvard Medical School–led team has shown that a soluble form of FLT1 causes about one-third of peripartum cardiomyopathy cases—those associated with pre-eclampsia. Ongoing studies are seeking to identify small molecule inhibitors of the protein and determine whether the mechanism also underlies the other two-thirds of cases.
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Getting selective for γ
Tim Fulmer
doi:10.1038/scibx.2012.539
Cellzome and Exelixis have independently designed the first highly selective inhibitors of the γ-isoform of PI3K. Exelixis hopes to out-license its inhibitors, whereas the recent acquisition of Cellzome by GlaxoSmithKline gives the pharma a new class of compounds for inflammatory and autoimmune diseases.
Full Text | PDF

Distillery: Therapeutics

Cancer

Top

BRAF; cyclin dependent kinase inhibitor 2A (CDKN2A; INK4a; ARF; p16INK4a); cyclin dependent kinase 4 (CDK4); CDK6
doi:10.1038/scibx.2012.540
Mouse studies suggest a BRAF inhibitor plus a CDK4 and CDK6 inhibitor could help treat pediatric astrocytomas that carry the BRAF V600E mutation and have a CDKN2A deficiency.
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DNA
doi:10.1038/scibx.2012.541
Mouse and cell culture studies identified mithramycin analogs that could help treat cancer.
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K-Ras; son of sevenless homolog 1 (SOS1)
doi:10.1038/scibx.2012.542
Two independent in vitro studies identified a previously unknown binding site on K-Ras that could be targeted with small molecules to treat cancer.
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P glycoprotein (MDR1; ABCB1; P-gp; CD243)
doi:10.1038/scibx.2012.543
Cell culture studies identified ecdysteroid compounds that could help treat multidrug-resistant (MDR) cancers.
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p21 Protein (Cdc42 Rac)-activated kinase 4 (PAK4)
doi:10.1038/scibx.2012.544
In vitro and rodent studies identified a pyrroloaminopyrazole series of PAK4 inhibitors that could help treat cancers.
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Sirtuin 7 (SIRT7)
doi:10.1038/scibx.2012.545
In vitro and mouse studies suggest inhibiting SIRT7 could help treat cancer.
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Topoisomerase I (TOP1); tyrosyl-DNA phosphodiesterase 1 (TDP1)
doi:10.1038/scibx.2012.546
In vitro studies identified a bis(indenoisoquinoline)-based inhibitor of TOP1 and TDP1 that could help treat cancer.
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Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2)
doi:10.1038/scibx.2012.547
Genomic and mouse studies identified PREX2 mutants in melanomas that could be inhibited to help treat the cancer.
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Tyrosine kinase non-receptor 2 (Tnk2; ACK1)
doi:10.1038/scibx.2012.548
Mouse and cell culture studies suggest inhibiting ACK1 could help reverse resistance to radiotherapy in castration-resistant prostate cancer (CRPC).
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Survivin (BIRC5)
doi:10.1038/scibx.2012.549
Mouse studies suggest survivin inhibitors could help treat Merkel cell carcinoma, a form of skin cancer caused by the Merkel cell polyomavirus.
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NAD(P)H dehydrogenase quinine 1 (NQO1; QR1)
doi:10.1038/scibx.2012.550
In vitro and mouse studies identified deoxynyboquinone (DNQ) as a new NQO1 substrate that could help treat solid tumors.
Full Text | PDF

Cardiovascular disease

Top

Protein disulfide isomerase (PDI)
doi:10.1038/scibx.2012.551
In vitro and mouse studies identified a PDI inhibitor that could help prevent thrombosis.
Full Text | PDF

Endocrine/metabolic disease

Top

Aldehyde dehydrogenase 1 family member A1 (ALDH1A1)
doi:10.1038/scibx.2012.552
Mice and human tissue studies suggest antagonizing ALDH1A1 could help treat obesity and type 2 diabetes.
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Musculoskeletal disease

Top

Family with sequence similarity 20 member C (FAM20C)
doi:10.1038/scibx.2012.553
In vitro studies identified FAM20C as a protein kinase that phosphorylates extracellular proteins and that could be targeted to treat Raine syndrome, a rare congenital disorder characterized by lethal bone dysplasias.
Full Text | PDF

Neurology

Top

β-Amyloid 42 (Aβ42)
doi:10.1038/scibx.2012.554
In vitro and mouse studies suggest inhibiting a pyroglutamylated form of Aβ42 could help treat AD.
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Not applicable
doi:10.1038/scibx.2012.555
A clinical study suggests epilepsy drugs could be useful for treating or preventing AD.
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Metabotropic glutamate receptor subtype 5 (mGluR5; GRM5)
doi:10.1038/scibx.2012.556
Studies in mice suggest antagonizing mGluR5 could help treat autism.
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Methylglyoxal; NaV1.8 (PN3; SCN10A)
doi:10.1038/scibx.2012.557
Human and mouse studies suggest inhibiting the metabolite methylglyoxal could help treat hyperalgesia in diabetic neuropathy.
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UbiA prenyltransferase domain containing 1 (UBIAD1)
doi:10.1038/scibx.2012.558
Drosophila studies suggest improving vitamin K2 production could help treat diseases involving mitochondrial dysfunction, including PD.
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Transglutaminase 1 (TGM1; TG1); TGM2 (TG2)
doi:10.1038/scibx.2012.559
Studies in mice and in cultured neurons suggest inhibiting TGM1 and TGM2 could be neuroprotective after stroke.
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Distillery: Techniques

Assays and screens

Top

High throughput screening of T cell receptor (TCR) to detect minimal residual disease (MRD) in T cell acute lymphoblastic leukemia (T-ALL)
doi:10.1038/scibx.2012.560
High throughput screening of lymphoid receptor genes could help guide diagnosis and prognosis in T-ALL.
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Proteomic method for developing rational combinations of kinase inhibitors
doi:10.1038/scibx.2012.561
A proteomic method could aid the development of rational combinations of kinase inhibitors to treat cancer.
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Chemistry

Top

Synthesis of biologically active meroterpenoids
doi:10.1038/scibx.2012.562
A method of synthesizing meroterpenoids could generate new compounds to treat cancer and infectious diseases.
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Drug platforms

Top

Protocol for augmenting β cell regeneration and reversing late-stage type 1 diabetes
doi:10.1038/scibx.2012.563
A protocol using an antibody and a cell transplant conditioning regimen plus delivery of gastrin and epidermal growth factor (EGF) could help treat late-stage type 1 diabetes.
Full Text | PDF

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