Friday, February 21, 2014

FDA Accepts Filing of NDA for IV Antibiotic Oritavancin with Priority Review

Oritavancin (INN, also known as LY333328) is a novel semi-synthetic glycopeptide antibiotic being developed for the treatment of serious Gram-positive infections. Originally discovered and developed by Eli Lilly, oritavancin was acquired by InterMune in 2001 and then by Targanta Therapeutics in late 2005.

In Dec 2008 the FDA declined to approve it, and an EU application was withdrawn. In 2009 the development rights were acquired by The Medicine Co. who are running clinical trials for a possible new FDA application in 2013

Wednesday, February 19, 2014

Small molecules stop cervical cancer virus assembling

Researchers in China have disrupted the life cycle of the leading cause of cervical cancer – the human papilloma virus – using a macrocyclic molecule called a pillarene. The team hope their findings will offer new prophylactic avenues against the virus.

The pillarene derivative, CP5A, was tested as it is known to have high water solubility and show selective binding towards basic amino acids, like l-Lysine, l-arginine and l-histidine. Because of these properties, CP5A binds to the exposed basic amino acids in protein L1, preventing pentamer formation, and therefore stopping the creation of viral particles.

The team hope to screen other small molecules to find inhibitors for more specific binding sites on the interface between L1 and L2. Their long term aim is to use one of these to produce a HPV vaccine.

Ref :!divAbstract

Tuesday, February 18, 2014

Old FDA-approved drugs may hold promise for treatment of rare, drug-resistant cancer

After studying how samples of GIST responded to various concentrations of the 89 drugs in the laboratory, Dr. Duensing and her colleagues identified 37 compounds that showed some anticancer activity in at least one of the concentrations tested. Importantly, they noted that the most promising candidates all belonged to only two major drug classes: inhibitors of gene transcription and so-called topoisomerase II inhibitors. Based on these findings, the research team selected the two most promising compounds for further testing - gene transcription inhibitor mithramycin A (left structure below) , which is in clinical trials to treat Ewing sarcoma, and topoisomerase II inhibitor mitoxantrone (beow right structure), which is used in metastatic breast cancer and leukemia.

Both drugs were highly effective in fighting GIST in laboratory tests. Moreover, the mechanism of action of each drug was linked to the specific underlying biology of these tumors.

"These are very encouraging results," said Dr. Duensing. "The next step will be moving our findings to clinical exploration to see if the results we found in the lab hold up in patients."

Old FDA-approved drugs may hold promise for treatment of rare, drug-resistant cancer

Ref :

Sunday, February 16, 2014

FDA-approved drug pregabalin effectively treats RLS symptoms with less side effects

In continuation of my update on pregabalin

A report in the Feb. 13 New England Journal of Medicine confirms previous studies suggesting that long-term treatment with the type of drugs commonly prescribed to treat restless leg syndrome (RLS) can cause a serious worsening of the condition in some patients. The year-long study from a multi-institutional research team found that pregabalin - which is FDA-approved to treat nerve pain, seizures, and other conditions - was effective in reducing RLS symptoms and was much less likely to cause symptom worsening than pramipexole, one of several drugs that activate the dopamine neurotransmission system and are FDA approved for treatment of RLS.

"Our key finding is that dopaminergic drugs, while very effective for many people with RLS, can worsen symptoms in some patients over time, while non-dopaminergic pregabalin is not associated with this disturbing side effect," says John Winkelman, MD, PhD, of the Massachusetts General Hospital Department of Psychiatry, senior author of the study. "Those treating RLS patients with dopaminergic drugs need to be aware of this common complication and exercise caution if their symptoms worsen."

Wednesday, February 5, 2014

Melatonin shows potential to slow tumor growth in certain breast cancers

An  early stage study shows melatonin   a hormone that regulates the body's sleep and awake cycles  may have the potential to help slow the growth of certain breast cancer tumors, according to researchers from Henry Ford Hospital in Detroit and Foundation for Research Support of the State of São Paulo.

Tuesday, February 4, 2014

Geranium extracts inhibit HIV-1

Extracts of the geranium plant Pelargonium sidoides inactivate human immunodeficiency virus type 1 (HIV-1) and prevent the virus from invading human cells. Scientists report that these extracts represent a potential new class of anti-HIV-1 agents for the treatment of AIDS.

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Sunday, February 2, 2014

Biotechdaily - Nilotinib Enhances Toxic Protein Removal from Parkinson's Disease Neurons

In continuation of my update on Nilotinib

The anticancer drug nilotinib induces clearance of the toxic protein alpha-synuclein from   neurons in a mouse model of Parkinson's disease and ameliorates symptoms of the disease.

Investigators at Georgetown University Medical Center (Washington DC, USA) worked with a mouse model of Parkinson’s disease. They reported in the May 10, 2013, online edition of the journal Human Molecular Genetics that lentiviral transfection of the gene encoding alpha-synuclein into the mouse SN lead to activation (phosphorylation) of the tyrosine kinase Abl and that lentiviral transfection of the gene encoding Abl increased alpha-synuclein levels, which exacerbated the disease. Administration of the tyrosine-kinase inhibitor nilotinib decreased Abl activity and increased autophagic clearance of alpha-synuclein into lysosomes in transgenic and lentiviral gene-transfer models.

The drug nilotinib was approved as Tasigna in the USA and the EU for drug-resistant chronic myelogenous leukemia (CML). In 2006, a Phase I clinical trial found that nilotinib had a relatively favorable safety profile and showed activity in cases of CML resistant to treatment with imatinib (Gleevec [USA]/ Glivec [Europe, Australia, and Latin America]), another tyrosine kinase inhibitor currently used as a first-line treatment. In that study, 92% of patients (already resistant or unresponsive to imatinib) achieved a normal white blood cell counts after five months of treatment.

In the current study, nilotinib, which enters the brain within [US] Food and Drug Administration approved doses, led to autophagic degradation of alpha-synuclein, protection of SN neurons and improvement of motor performance in the Parkinson’s disease mice.

"No one has tried anything like this before," said senior author Dr. Charbel E-H Moussa, assistant professor of neuroscience at the Georgetown University Medical Center. "This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell. By clearing intracellular proteins, the drug prevents their accumulation in pathological inclusions called Lewy bodies and/or tangles, and also prevents amyloid secretion into the extracellular space between neurons, so proteins do not form toxic clumps or plaques in the brain."

"The doses used to treat CML are high enough that the drug pushes cells to chew up their own internal organelles, causing self-cannibalization and cell death," said Dr. Moussa. "We reasoned that small doses—for these mice, an equivalent to 1% of the dose used in humans—would turn on just enough autophagy in neurons that the cells would clear malfunctioning proteins, and nothing else. We successfully tested this for several diseases models that have an accumulation of intracellular protein. It gets rid of alpha-synuclein and tau in a number of movement disorders, such as Parkinson's disease as well as Lewy body dementia."