Discovery Of Novel New Class of Antimicrobial Agents... ......

We know that most of the bacteria are getting resistant to the present drugs and there is an urgent need to find a solution for resistant bacteria. Inn this global fight against resistant bacteria many companies are trying different ways and now Chaperone Technologies, Inc has come up with something innovative and interesting way, i.e., the company is trying to develop antimicrobial compounds that work by inhibiting bacterial hsp70 proteins (an entirely new mechanism of action).

Chaperone’s antimicrobial program focuses on development of peptide as well as small molecule hsp70 inhibitor drugs that block the effect of this important class of molecular “chaperones” whose role is to help mediate or respond to toxic misfolded proteins within bacteria. Inhibition of this critical bacterial protein has been proven to kill bacterial pathogens. Besides antimicrobials, the inhibition of hsp70 molecular chaperone proteins present in other cell-types has a range of therapeutic applications that are being investigated by the company.

Using sophisticated computerized molecular modeling techniques, proprietary high-throughput screening tools developed by Chaperone and other approaches, the company has significantly expanded its library of novel hsp70 inhibitor compounds including CHP-267 and CHP-281, just two of the many promising drug candidates from this highly promising family of small molecule inhibitors discovered by the Company. Chaperone is looking at hsp70 inhibitors as stand alone antimicrobial agents as well as in combination with other antimicrobials (e.g., Finafloxacin.HCl : see the structure -which is under phase II clinical trials). The company recently received a US Patent covering a method of significantly amplifying the effectiveness of other antimicrobials by combining their use with that of an hsp70 inhibitor. Combining a bacterial hsp70 inhibitor with another antimicrobial yields increased bacterial killing of clinically important pathogens and the potential for combination therapy.

Chaperone’s drug candidates have been proven effective against dangerous bacteria such as MRSA, acinetobacter, and vancomycin resistant enterococci. When combined with other antibiotics, Chaperone’s compounds stimulate powerful antibiotic synergy, providing superior efficacy even while using significantly lower doses of the combined agents.

Source : http://www.biospace.com/news_story.aspx?NewsEntityId=118501

Combination of EGCG & DAPH-12 - a treatment for brain disorders ?

Amyloid plaques are tightly packed sheets of proteins that infiltrate the brain. These plaques, which are stable and seemingly impenetrable, fill nerve cells or wrap around brain tissues and eventually (as in the case of Alzheimer's) suffocate vital neurons or brain cells, causing loss of memory, language, motor function and eventually premature death.

To date, researchers have had no success in destroying plaques in the human brain and only minimal success in the laboratory. One reason for these difficulties in finding compounds that can dissolve amyloids is their immense stability and their complex composition.

Yet, Dr. Duennwald ( Boston Biomedical Research Institute , BBRI) and co workers from Pennsylvania School of Medicine, experienced success in previous studies when he exposed amyloids in living yeast cells to EGCG (see the above structure). Furthermore, he and his collaborators also found before that DAPH-12, (see below structure) too, inhibits amyloid production in yeast.

About EGCG :

Epigallocatechin gallate, also known as Epigallocatechin 3-gallate, is the ester of epigallocatechin and gallic acid and a type of catechin. EGCG is the most abundant catechin in most notably tea, among other plants, and is also a potent antioxidant and that may have therapeutic properties for many disorders including cancer. It is found in green tea, but not black tea, as EGCG is converted into thearubigins in black teas. EGCG can be found in many supplements.

These findings are significant because it is the first time a combination of specific chemicals (EGCG & DAPH-12) has successfully destroyed diverse forms of amyloids at the same time.

Though the detailed mechanism is still to be established, its a good achievement and hope this combinatorial therapy will help those sufferings from Alzheimer's and other degenerative diseases (Huntington's, and Parkinson's) in the days to come.....

Ref : http://www.nature.com/nchembio/journal/v5/n12/pdf/nchembio.246.pdf

Nizatidine as an Oral Solution.....

About Nizatidine :

Nizatidine is a histamine H₂-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). It was developed by Eli Lilly and is marketed under the trade names Tazac and Axid.


Recently FDA approved the Nizatidine Oral Solution in the 15 mg/mL strength. Nizatidine Oral Solution is the first available generic in oral solution form and marks Amneal’s fourth liquid approval. It represents the company’s first exclusive generic – Amneal has 180-day exclusivity to market the product beginning from the date of first shipment......

Source : http://www.amneal.com/headlines/archive/Nizatidine_Oral_Solution_12-04-09.pdf

Statins may protect against GVHD complications

Statins may protect against GVHD complications

First live targeting of tumors with RNA-based technology

Researchers at Duke University Medical Center have devised a way they might deliver the right therapy directly to tumors using special molecules, called aptamers, (Aptamers are oligonucleotides or peptide molecules that bind to a specific target molecule) which specifically bind to living tumor tissue.......

More....First live targeting of tumors with RNA-based technology

CASD-NMR a boon to structure validation....

CASD-NMR(Critical Assessment of Automated Structure Determination) of Proteins is a rolling community-wide experiment involving developers of software tools / protocols for the automated calculation of protein structures from NMR data. The goal of CASD-NMR is to help advance the relevant methodology in order to reach the level of quality and reliability required for direct structure deposition in the PDB. CASD-NMR will also produce extensive data sets that will be useful to develop better methods for NMR structure validation. The more significance of this project is : In the future, automation in NMR will allow 'unsupervised' results to be accepted by the community as being correct and viable, ready for inclusion in the Protein Data Bank (PDB) straight away. The PDB is a database that stores macromolecular structural data that is freely and publicly available for further research.

Ref : http://www.e-nmr.eu/CASD-NMR

New target for diabtes type 2 treatment ?

Mitochondria provide energy for cellular activity. Mitochondrial damage causes people with type 2 diabetes to lose insulin-producing cells, a finding that could lead to new treatments, researchers say.

The researchers (Dr. E. Dale Abel, chief of the endocrinology and metabolism division at the University of Utah School of Medicine in Salt Lake City) found that when insulin-producing beta cells in the pancreas can't respond to circulating insulin, it triggers a "molecular cascade" that damages the normal action of a certain molecular receptor on the surface of the mitochondria. The damaged mitochondria then begin to destroy adenosine triphosphate, the prime fuel for cellular activity. As a result, the beta cells die.

The study provides novel insights into the role of insulin signaling in the regulation of the BAD/GK complex, glycolytic enzyme activity and mitochondrial metabolism in pancreatic β-cells. Ser112-BAD_S and its upstream kinases may be potential targets for the maintenance of the BAD/GK complex that is necessary for normal mitochondrial function and the regulation of β-cell survival....

Source : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007983

CCII capsules offer safe and effective treatment for rheumatoid arthritis

Chicken collagen can provide relief from rheumatoid arthritis (RA) symptoms. A randomised, controlled trial, published in BioMed Central's open access journal Arthritis Research & Therapy, has found that Chicken type II collagen (CCII), a protein extracted from the cartilage of chicken breast, is a safe and effective treatment for RA.

More....CCII capsules offer safe and effective treatment for rheumatoid arthritis

Positive data from rose bengal disodium for psoriasis & atopic dermatitis....

Acid Red 94, (Rose Bengal sodium salt), 3,4,5,6-tetrachloro-2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate :

Provectus Pharmaceuticals, Inc announced preliminary data for the company’s PH-10 Phase 2 clinical trial for Psoriasis as well as for its Phase 2 clinical trial for Atopic Dermatitis. As per the claim by the company, in its Phase 2 trial of PH-10 (0.001% Rose Bengal) for psoriasis, preliminary data shows that 79% of 29 subjects in the clinical trial demonstrated improvement in the Psoriasis Scoring Index (PSI) during four weeks of daily treatment with PH-10. In addition, 83% of the subjects reported no or only mild pruritus (itching) by week four of the trial, with no significant safety issues noted. The 30^th and final subject will complete final evaluation in early December.

In its Phase 2 trial of PH-10 for atopic dermatitis (“eczema”), preliminary data from the first 18 subjects indicated that 94% of subjects had improvement in the Eczema Area Severity Index (EASI) during four weeks of treatment. Subjects applied PH-10 daily for up to four weeks to skin areas affected by atopic dermatitis, with response observed weekly throughout this treatment phase and for one month after the end of this period. As in the psoriasis study, the treatments were generally well tolerated with no significant safety issues identified. Hope a sigh of relief for those suffering from psoriasis and atopic dermatitis....

Ref : http://www.pvct.com/pressrelease.html?article=20091201

Positive Results from Chronic Study of Rivaroxaban (anticoagulant drug)...

Rivaroxaban, is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto. If approved by the United States FDA, it will be marketed by Ortho-McNeil Pharmaceutical. It is the first available orally active direct inhibitor of coagulation Factor Xa. Rivaroxaban is well absorbed from the gut and maximum inhibition of factor Xa occurs three hours after a dose. The effects lasts 8–12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible.

Rivaroxaban is undergoing review by the FDA, On March 19, 2009, an advisory panel recommended FDA approval of rivaroxaban 10 mg once daily for use in patients undergoing hip or knee replacement surgery. The advisory panel concluded that the record trials demonstrate that rivaroxaban is non-inferior and possibly superior to subcutaneous enoxaparin 40 mg once daily. However, they also found an increased risk of bleeding with rivaroxaban and did not address the question of long-term (i.e. > 35 days) use. The advisory panel noted that 1 participant out of 6183 randomized to rivaroxaban died of liver toxicity.....

Source :http://abstracts.hematologylibrary.org/cgi/content/abstract/112/11/436?maxtoshow=&HITS=50&hits=50&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&displaysectionid=Oral+Session&fdate=1/1/2008&tdate=12/31/2008&resourcetype=HWCIT