USPTO issues patent to MicuRx’s MRX-I antibacterial agent

USPTO issues patent to MicuRx’s MRX-I antibacterial agent: MicuRx Pharmaceuticals, Inc., a privately-held biopharmaceutical company developing next-generation antibiotics, today announced that the U.S. Patent and Trademark Office (USPTO) issued a composition of matter patent covering its clinical candidate, MRX-I. MRX-I is a novel antibacterial oxazolidinone (general structure of 2-oxazolidinone) that targets infections due to multi-drug resistant Gram-positive pathogens.

Azithromycin can be effective treatment option for patients with BOS

In continuation of my update on azithromycin

Azithromycin can be effective treatment option for patients with BOS: Researchers in the United Kingdom have determined that azithromycin, a broad-spectrum antibiotic that also has anti-inflammatory properties, can be an effective treatment option for patients suffering from bronchiolitis obliterans syndrome (BOS), a life-threatening complication that occurs in the majority of patients following lung transplantation.

Positive Results from Tesetaxel Study

Genta Incorporated announced results from its Phase 2 clinical trial using tesetaxel as initial, single-agent chemotherapy in women with  advanced breast cancer. Tesetaxel is an oral taxane in clinical development. The trial is lead by Memorial Sloan-Kettering Cancer Center, New York, NY, in collaboration with three other US centers.

Women were eligible if they had not received chemotherapy for locally advanced or metastatic HER2-negative breast cancer. Prior adjuvant chemotherapy was allowed if the recurrence was at least 12 months from the last dose. Forty-six patients were accrued to the trial, and 44 are currently evaluable for response. 70% of patients had received adjuvant chemotherapy; more than 80% of those regimens had included an injectable taxane. More than 50% of patients had received local radiotherapy, and approximately two-thirds had progressed on one more hormonal therapies.

Major objective responses were observed in 20 of 44 patients (45%), including one complete response and nineteen partial responses. Seven of the major responders cleared more than 75% of their measurable disease. The disease-control/clinical-benefit rate, which includes major responders and patients with stable disease, was 82%.

Exploratory analyses showed that 17 of 35 patients (49%) whose disease was estrogen receptor positive (ER+) had major responses. Median progression-free survival in the ER+ population was 7.3 months. In women with "triple-negative" disease, which is relatively insensitive to chemotherapy, 3 of 9 patients responded 33%.

Tivantinib Meets Study Endpoint

ArQule Inc. and Daiichi Sankyo Co. Ltd. announced that a Phase 2 trial data using tivantinib as a single agent investigational second-line treatment in hepatocellular carcinoma (HCC) met its primary endpoint. Now the full results from this trial will be presented at the 2012 Annual Meeting of American Society of Clinical Oncology, including positive data in the pre-defined c-MET high population. Additional clinical data with tivantinib will be featured in two poster discussions and two general poster sessions.

“These findings represent the first randomized data reported with an investigational c-MET inhibitor administered as a single agent second-line treatment in HCC,” said Paolo Pucci, chief executive officer of ArQule. “They clearly define c-MET high patients as a biological subgroup for potential targeted therapy with tivantinib. The robust statistical significance achieved in this trial reflects the anti-cancer activity of tivantinib alone and expands its therapeutic potential.”

Data from the HCC trial demonstrated a statistically significant improvement in time-to-progression (HR=0.43, log rank p-value=0.03), accompanied by significant improvements in progression-free survival and disease control rate among second-line patients with c-MET high tumors who were treated with tivantinib. In addition, overall survival data were observed favoring tivantinib-treated patients in this population. Efficacy was similar in the two tivantinib dosing subgroups (360 milligrams twice daily and 240 milligrams twice daily), with less frequent neutropenia in the lower dose.

Previously announced top-line data from the HCC trial demonstrate that treatment with tivantinib produced a statistically significant 56 percent improvement in TTP in the intent-to-treat (ITT) population by central radiology review, the primary endpoint (HR = 0.64, log rank p-value = 0.04) in this trial. Adverse events were reported at similar rates in the treatment and placebo arms, except for a higher incidence of fatigue and hematologic events, including neutropenia and anemia, in tivantinib-treated patients. The incidence of hematologic events declined following dose reduction of tivantinib from 360 milligrams twice daily to 240 milligrams twice daily.

Ref : http://investors.arqule.com/releasedetail.cfm?ReleaseID=674815

New anti-cancer drug developed

New anti-cancer drug developed

Successful Completion Of Proof-of-concept Clinical Trial Of Levotofisopam For The Treatment Of Gout

Pharmos Corporation,  announced that it has successfully completed a proof-of-concept clinical trial using its compound levotofisopam (5S)-1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine, S-tofisopam see structure below) to treat patients with hyperuricemia and gout. This phase 2a trial was conducted at the Duke Clinical Research Unit of Duke University and the principal investigator was John Sundy, MD, PhD, an expert and key opinion leader in the treatment of gout. The trial was designed to assess the safety and efficacy of levotofisopam as a uric acid-lowering agent in patients with gout.

The trial enrolled 13 patients in an open label study with patients confined in the Duke facility.  The study enrolled patients with screening serum urate between 8 and 12 mg/dL. Subjects received a single dose of 50 mg on days 1 and 7 and 50 mg TID on days 2 through 6.  Levotofisopam was well tolerated. The mean reduction in serum urate was over 45%. All 13 patients were responders, and demonstrated a serum urate level of less than 6 mg/dL on day 7. Seven subjects achieved a serum urate level less than 4 mg/dL on day 7. Additionally there was an increase in the fractional excretion of urate, confirming the compound's mechanism of action as a uricosuric agent that enhances urate excretion by the kidneys. 

Commenting on the results of this Phase 2a trial, the principal investigator Dr. John Sundy said, "monotherapy with levotofisopam was well tolerated and induced clinically important reductions in serum urate levels in all patients studied. These results support further development of levotofisopam for treating hyperuricemia in patients with gout."

Achillion Announces Additional Proof-of-Concept Data With ACH-2684 for the Treatment of Hepatitis C

Achillion Announces Additional Proof-of-Concept Data With ACH-2684 for the Treatment of Hepatitis C: Achieves Up to 3.73 log10 Reduction in Genotype 1 HCV RNA After Three Days of Treatment With Once-Daily 400 mg ACH-2684 in Phase 1b Study : Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today reported...

Achillion Pharmaceuticals, Inc. reported proof-of-concept data from a Phase 1b clinical trial demonstrating that patients with chronic hepatitis C (HCV) genotype 1 (GT 1) treated with ACH-2684 (see below structure), a second-generation protease inhibitor, achieved a mean maximum 3.73 log10 reduction in HCV RNA after three-day 400 mg monotherapy with once-daily (QD) dosing. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with HCV.

 "We believe ACH-2684, with its potent antiviral activity achieved without boosting and once-daily dosing, is one of the most intriguing protease inhibitors in clinical development for the treatment of HCV,"...

Heparin-like compounds inhibit breast cancer metastasis to bone

Heparin-like compounds inhibit breast cancer metastasis to bone: Researchers from VTT Technical Research Centre of Finland have in collaboration with the University of Turku, Indiana University and two Finnish companies, Biotie Therapies Corp. and Pharmatest Services Ltd, discovered a novel mechanism regulating...

Researchers,  subsequently showed how heparin and a high-molecular-weight Escherichia coli K5-derived heparin-like polysaccharide (K5-NSOS see below structure) inhibited TGF-β–induced IL-11 production in MDA-MB-231(SA) cells. In addition, K5-NSOS inhibited bone resorption activity of human osteoclasts in vitro. We evaluated the therapeutic potential of K5-NSOS and fragmin in a mouse model of breast cancer bone metastasis. MDA-MB-231(SA) cells were inoculated into the left cardiac ventricle of athymic nude mice which were treated with fragmin, K5-NSOS, or vehicle once a day for four weeks. Both heparin-like glycosaminoglycans inhibited weight reduction, decreased osteolytic lesion area, and reduced tumor burden in bone. In conclusion, our data imply novel mechanisms involved in TGF-β induction and support the critical role of heparan sulfate glycosaminoglycans in cancer metastasis as well as indicate that K5-NSOS is a potential antimetastatic and antiresorptive agent for cancer therapy. This study illustrates the potential to translate in vitro siRNA screening results toward in vivo therapeutic concepts.

 

Ref : http://mcr.aacrjournals.org/content/10/5/597.abstract

NSAIDs and Cardiovascular Risk Explained, According to Studies from the Perelman School of Medicine

NSAIDs and Cardiovascular Risk Explained, According to Studies from the Perelman School of Medicine: After nearly 13 years of study and intense debate, a pair of new papers from the Perelman School of Medicine, at the University of Pennsylvania have confirmed exactly how a once-popular class of anti-inflammatory drugs leads to cardiovascular risk for people taking...

Ref : http://www.uphs.upenn.edu/news/News_Releases/2012/05/risk/

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target

Research by a collaborative group of scientists from UC San Diego School of Medicine, UC San Francisco and Wake Forest School of Medicine has led to identification of an existing drug that is effective against Entamoeba histolytica. Using a high-throughput screen for drugs developed by the research team, they discovered that auranofin (see structure) a drug approved by the US Food and Drug Administration 25 years ago for rheumatoid arthritis -- is very effective in targeting an enzyme that protects amebae from oxygen attack (thus enhancing sensitivity of the amebae to reactive oxygen-mediated killing).

Entamoeba histolytica is a protozoan intestinal parasite that causes human amebiasis, the world's fourth leading cause of death from protozoan parasites. It is listed by the National Institutes of Health as a category B priority biodefense pathogen. Current treatment relies on metronidazole, which has adverse effects, and potential resistance to the drug is an increasing concern.

Study shows how a drug-lead compound suppresses tumour formation

Study shows how a drug-lead compound suppresses tumour formation: A team of scientists from the National University of Singapore's (NUS) Department of Biological Sciences and Mechanobiology Institute have discovered how a drug-led compound - a compound that is undergoing preclinical trials as a potential drug - can deprive cancer cells of energy and stop them from growing into a tumour. This drug-led compound is named BPTES (see below structure). This is the the first detailed descriptions of precisely how BPTES inhibits glutaminase....

 

Ref : http://www.pnas.org/content/109/20/7705.full

Scientists unravel action mechanism of castor oil

Scientists unravel action mechanism of castor oil: Castor oil is known primarily as an effective laxative; however, it was also used in ancient times with pregnant women to induce labour. Only now have scientists at the Max Planck Institute for Heart and Lung Research succeeded in unravelling the mysteries of the action mechanism. A receptor by the name of EP3 on the cells of the intestine and uterus is apparently responsible. This is activated by an ingredient, i.e., Ricinoleic acid (12-hydroxy-9-cis-octadecenoic acid) is an unsaturated omega-9 fatty acid in the oil, see the structure).

More : http://www.mpg.de/5808639/receptor_castor_oil

New Blood Thinner May Lower Chances of Clots in High-Risk Heart Patients: FDA

In continuation of my update on Rivaroxaban

New Blood Thinner May Lower Chances of Clots in High-Risk Heart Patients: FDA:  The new blood thinner Xarelto appears to lower the chances of potentially fatal blood clots in high-risk heart patients, a U.S. Food and Drug Administration review has found.

Cobiprostone shows promise against NSAID-induced gastric mucosal injury

Cobiprostone shows promise against NSAID-induced gastric mucosal injury: Sucampo Pharmaceuticals, Inc. today announced the presentation of preclinical data at Digestive Disease Week 2012, in San Diego, which demonstrates the protective effect of cobiprostone (see structure)  against epithelial barrier dysfunction in models of non-steroidal anti-inflammatory drug (NSAID)-induced gastric mucosal injury.

Ref : http://investor.sucampo.com/phoenix.zhtml?c=201197&p=irol-newsArticle&ID=1697806&highlight=

Pernix Therapeutics introduces Omeclamox-Pak® for the treatment of H. pylori infection and duodenal ulcer disease

Pernix Therapeutics introduces Omeclamox-Pak® for the treatment of H. pylori infection and duodenal ulcer disease: Pernix Therapeutics Holdings, Inc., a specialty pharmaceutical company,  announced the introduction of Omeclamox-Pak®, a ten-day therapy of omeprazole (below 1st) delayed-release capsules (20 mg), clarithromycin (below 2nd) tablets (500 mg) and amoxicillin (below 3rd) capsules (500 mg) for the treatment of Helicobacter pylori (H. pylori) infection and duodenal ulcer disease (active or one-year history) to eradicate H. pylori in adult patients...