Reduced melatonin levels linked to greater diabetes risk - Life Extension Update

In continuation of my update on Melatonin....

"Melatonin receptors have been found throughout the body in many tissues including pancreatic islet cells, reflecting the widespread effects of melatonin on physiological functions such as energy metabolism and the regulation of body weight," Ciaran McMullan and colleagues at Brigham and Women's Hospital noted in their introduction to the article. "Loss-of-function mutations in the melatonin receptor are associated with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional analysis of persons without diabetes, lower nocturnal melatonin secretion was associated with increased insulin resistance."

The researchers matched 370 women who developed diabetes while enrolled in the Nurses' Health Study with 370 nondiabetic participants. Morning urine samples obtained upon enrollment in 2000 were analyzed for the ratio of 6-sulfoxymelatonin (the major metabolite of melatonin) to creatinine in order to estimate overnight melatonin secretion.

Women with diabetes had a 6-sulfatoxymelatonin to creatinine ratio that was significantly lower than that of the control group. Among those whose ratio was among the lowest of the participants, the adjusted risk of developing diabetes was more than twice that of women whose ratio was among the highest group.

"This is the first time that an independent association has been established between nocturnal melatonin secretion and type 2 diabetes risk," announced Dr McMullan, who is a researcher in the Renal Division and Kidney Clinical Research Institute at BWH. "Hopefully this study will prompt future research to examine what influences a person's melatonin secretion and what is melatonin's role in altering a person's glucose metabolism and risk of diabetes."

"It is interesting to postulate from these data, in combination with prior literature, whether there is a causal role for reduced melatonin secretion in diabetes risk," the authors remark. "Further studies are needed to determine whether increasing melatonin levels (endogenously via prolonged nighttime dark exposure or exogenously via supplementation) can increase insulin sensitivity and decrease the incidence of type 2 diabetes."

Ref : http://jama.jamanetwork.com/article.aspx?articleid=1674239

Reduced melatonin levels linked to greater diabetes risk - Life Extension Update

FDA Approves Invokana to Treat Type 2 Diabetes

In continuation of my update on Canagliflozin

We know that, Canagliflozin (Invokana) is drug for the treatment of type 2 diabetes developed by Johnson & Johnson. In March 2013,  canagliflozin became the first in a new class of drugs for diabetes treatment to be approved. It is an inhibitor of subtype 2 sodium-glucose transport protein (SGLT2), which is responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter causes blood glucose to be eliminated through the urine..

FDA Approves Invokana to Treat Type 2 Diabetes

Ganetespib Shows Potency Against Lung Cancer

In continuation of my update on Ganetespib

Ganetespib Shows Potency Against Lung Cancer

FDA Approves Stivarga for Advanced Gastrointestinal Stromal Tumors

In continuation of my update on Stivagra

We know that, Regorafenib (BAY 73-4506, commercial name Stivarga) is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase (RTK). Regorafenib shows anti-angiogenic activity due to its dual targeted VEGFR2-TIE2 tyrosine kinase inhibition. It is currently being studied as a potential treatment option in multiple tumor types.

Now...

FDA Approves Stivarga for Advanced Gastrointestinal Stromal Tumors

FDA Approves Tecfidera - a New Treatment for Multiple Sclerosis

We know that, Dimethyl fumarate (DMF) is the methyl ester of fumaric acid. DMF was initially recognized as a very effective hypoxic cellradiosensitizer. Later, DMF combined with three other fumaric acid esters (FAE) was licensed in Germany as oral therapy for psoriasis (Fumaderm). Other diseases, such as necrobiosis lipoidica, granuloma annulare, and sarcoidosis were also found to respond to treatment with DMF in case reports or small patient series. Recently, phase III clinical trials found that DMF (BG-12) successfully reduced relapse rate and time to progression of disability in multiple sclerosis. DMF is thought to haveimmunomodulatory properties without significant immunosuppression.

In a non-medical use, DMF was applied as a biocide in furniture or shoes to prevent growths of mold during storage or transport in a humid climate. However, due to incidences of allergic reactions after skin contact the European Union banned DMF in consumer products since 1998, and since January 2009 the import of products containing DMF was also banned...

Now...

FDA Approves Tecfidera - a New Treatment for Multiple Sclerosis

FDA Approves Kadcyla for Late-Stage Breast Cancer

We know that, Trastuzumab emtansine  in the United States, ado-trastuzumab emtansine, trade name Kadcyla) is anantibody-drug conjugate consisting of the monoclonal antibody trastuzumab (Herceptin) linked to the cytotoxic agentmertansine (DM1). Trastuzumab alone stops growth of cancer cells by binding to the HER2/neu receptor, whereas mertansine enters cells and destroys them by binding to tubulin. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the toxin specifically to tumor cells.

In the EMILIA clinical trial of women with advanced HER2 positive breast cancer who were already resistant to trastuzumab alone, it improved survival by 5.8 months compared to the combination of lapatinib and capecitabine. Based on that trial, the U.S. Food and Drug Administration (FDA) approved marketing on February 22, 2013.

Trastuzumab emtansine was developed by Genentech. The planned cost is expected to be $9,800 a month, or $94,000 for a typical course of treatment..

Now....

FDA Approves Kadcyla for Late-Stage Breast Cancer

Warner Chilcott Announces FDA Approval of New Ulcerative Colitis Product Delzicol

We know that, Mesalazine , also known as mesalamine (USAN) or 5-aminosalicylic acid (5-ASA), is an anti-inflammatory drug used to treat inflammatory bowel disease, such as ulcerative colitis and mild-to-moderate Crohn's disease. Mesalazine is a bowel-specificaminosalicylate drug that acts locally in the gut and has its predominant actions there, thereby having few systemic side effects.

As a derivative of salicylic acid, mesalazine is also thought to be an antioxidant that traps free radicals, which are potentially damaging byproducts of metabolism

Warner Chilcott plc announced that the United States Food and Drug Administration (FDA) has approved its new 400 mg mesalamine product indicated for the treatment of ulcerative colitis. The product will be marketed as Delzicol (mesalamine) 400 mg delayed-release capsules. The Company anticipates that it will commercially launch Delzicol in March 2013.

Warner Chilcott Announces FDA Approval of New Ulcerative Colitis Product Delzicol

Takeda Receives FDA Approval for Kazano (alogliptin and metformin) for Type 2 Diabetes

Takeda Pharmaceuticals U.S.A., Inc. today announced that the United States (U.S.) Food and Drug Administration (FDA) has approved Kazano (alogliptin and metformin HCl) for the treatment of type 2 diabetes in adults as adjuncts to diet and exercise. 

Kazano contains alogliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i) that is designed to slow the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). Kazano combines alogliptin with metformin HCl, a widely used anti-diabetes medication, in a single tablet.

The most common adverse events (greater than or equal to 4%) reported with alogliptin include nasopharyngitis, headache and upper respiratory tract infection. Common adverse events (greater than or equal to 4%) reported with Kazano include upper respiratory tract infection, nasopharyngitis, diarrhea, hypertension, headache, back pain and urinary tract infection.

Takeda is committed to providing type 2 diabetes patients with treatment options that help address their needs, and is planning to commercially launch Kazano in the summer of 2013.

Takeda's consolidated financial statements for the 2012 fiscal year will not be impacted by the FDA approvals.

Takeda Receives FDA Approval for Kazano (alogliptin and metformin) for Type 2 Diabetes

FDA Approves Exjade to Remove Excess Iron in Patients with Genetic Blood Disorder

In continuation of my update on Deferasirox

We know that, Deferasirox (marketed as Exjade) is a rationally-designed oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is the first oral medication approved in the USA for this purpose.

It was approved by the United States Food and Drug Administration (FDA) in November 2005. According to FDA (May 2007), renal failure and cytopenias have been reported in patients receiving deferasirox oral suspension tablets. It is approved in the European Union by the European Medicines Agency (EMA) for children 6 years and older for chronic iron overload from repeated blood transfusions.....

FDA Approves Exjade to Remove Excess Iron in Patients with Genetic Blood Disorder

Santarus Receives FDA Approval of Uceris (budesonide) for the Induction of Remission in Patients with Active, Mild to Moderate Ulcerative Colitis

In continuation of my update on Budesonide

We know that, Budesonide is a glucocorticoid steroid for the treatment of asthma and non-infectious rhinitis (including hay fever and other allergies), and for treatment and prevention of nasal polyposis. In addition, it is used for Crohn's disease (inflammatory bowel disease).

It is marketed by AstraZeneca as a nasal inhalant under the brand name Rhinocort (in Denmark, as Rhinosol), as an oral inhalant under the brand name Pulmicort (in Israel, Budicort), and as either an enema or a modified-release oral capsule under the brand name Entocort. It is also sold in combination with formoterol (Oxis) in a single inhaler, under the brand name Symbicort. In Brazil it is marketed by Eurofarma under the brand name Noex. Entocort EC is an oral capsule marketed in the United States by Prometheus Laboratories.

Santarus Receives FDA Approval of Uceris (budesonide) for the Induction of Remission in Patients with Active, Mild to Moderate Ulcerative Colitis

FDA Approves Sirturo to Treat Multi-Drug Resistant Tuberculosis

In continuation of my update on bedaquiline...

Sirturo is being approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides patients earlier access to promising new drugs while the company conducts additional studies to confirm the drug’s clinical benefit and safe use.

The FDA also granted Sirturo fast track designation, priority review and orphan-product designation. The drug demonstrated the potential to fill an unmet medical need, has the potential to provide safe and effective treatment where no satisfactory alternative therapy exists, and is intended to treat a rare disease, respectively.

Sirturo carries a Boxed Warning alerting patients and health care professionals that the drug can affect the heart’s electrical activity (QT prolongation), which could lead to an abnormal and potentially fatal heart rhythm. The Boxed Warning also notes deaths in patients treated with Sirturo. Nine patients who received Sirturo died compared with two patients who received placebo. Five of the deaths in the Sirturo group and all of the deaths in the placebo arm seemed to be related to tuberculosis, but no consistent reason for the deaths in the remaining Sirturo-treated patients could be identified.

Sirturo’s manufacturer, Janssen Therapeutics, will distribute the drug from a single source and will provide educational materials to help ensure the drug is used appropriately.

Sirturo’s safety and effectiveness were established in 440 patients in two Phase 2 clinical trials. Patients in the first trial were randomly assigned to be treated with Sirturo plus other drugs used to treat TB, or a placebo plus other drugs used to treat TB. All patients in the second trial, which is ongoing, received Sirturo plus other TB drugs. Both studies were designed to measure the length of time it took for a patient’s sputum to be free of M. tuberculosis (sputum culture conversion, or SCC).

FDA Approves Sirturo to Treat Multi-Drug Resistant Tuberculosis

FDA Approves Juxtapid - New Orphan Drug for Rare Cholesterol Disorder

In continuation of my update on lomitapide..

US FDA, Juxtapid (lomitapide) to reduce low-density lipoprotein (LDL) cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). Juxtapid is intended for use in combination with a low fat diet and other lipid-lowering treatments.

FDA Approves Juxtapid - New Orphan Drug for Rare Cholesterol Disorder

FDA Approves Adasuve (loxapine) Inhalation Powder for the Acute Treatment of Agitation Associated with Schizophrenia or Bipo...

In continuation of my update on adasuve

FDA Approves Adasuve (loxapine) Inhalation Powder for the Acute Treatment of Agitation Associated with Schizophrenia or Bipo...

Discovery could increase efficacy of promising cystic fibrosis drug

We know that, Ivacaftor (trade name Kalydeco, developed as VX-770) is a potentiator approved for patients with the G551D mutation of cystic fibrosis. Ivacaftor was developed by Vertex Pharmaceuticals in conjunction with the Cystic Fibrosis Foundation.

Cystic fibrosis is caused by any one of several defects in a protein, cystic fibrosis transmembrane conductance regulator, which regulates fluid flow within cells and affects the components of sweat, digestive fluids, and mucus. The defect, which is caused by a mutation in the individual's DNA, can be in any of several locations along the protein, each of which interferes with a different function of the protein. G551D is a standard amino acid abbreviation for a mutation in which the amino acid glycine (G) in position 551 is replaced with aspartic acid (D). G551D is characterized by a dysfunctional CFTR protein on the cell surface. In the case of G551D, the protein is trafficked to the correct area, the epithelial cell surface, but once there the protein cannot transport chloride through the channel. Ivacaftor, a CFTR potentiator, improves the transport of chloride through the ion channel by binding to the channels directly to induce a non-conventional mode of gating which in turn increases the probability that the channel is open.

Accidental discovery of a mutation in CFTR, the R532 mutation, allowed MU researchers to reveal a new "non-strict coupling" relationship that occurs between the consumption of ATP, a molecule that provides energy in the body, and the opening and closing of the CFTR. They argue that the new information uncovered about this mechanism that controls the opening and closing of the CFTR and the passage of ions through it could explain how and where the new cystic fibrosis treatment Kalydeco (Vx-770) works.

"To his credit, Dr. Hwang exploited the behavior of the CFTR mutants to demonstrate that CFTR's gate is not strictly coupled to the nucleotide binding engine (NBD) that binds and splits ATP [energy] to drive conformational changes that regulate chloride flow through the CFTR protein channel," said colleague David Sheppard, PhD, an associate professor in the School of Physiology and Pharmacology at the University of Bristol in Bristol, U.K. who did not participate in the study.

In their study, MU researchers were able to observe the effects of the cystic fibrosis drug Vx-770 on the recently discovered R352 mutation. They found that Vx-770 enhances the activity of the CFTR channel by exploiting this "non-coupling" mechanism, a conclusion also supported by experimental results with the wild-type CFTR protein.

"Traditionally, researchers have defined how energy is utilized and transferred in the CFTR as a 'strict coupling' mechanism, meaning that one ATP molecule opens CFTR's gate, ions pass through and the ATP molecule is hydrolyzed and then the gate closes," Hwang said. "In this new model, we argue that the CFTR uses energy from ATP hydrolysis to carry out its function of chloride flow, but this coupling mechanism is more plastic than we thought and therefore could be subjective to manipulations by drugs such as Vx-770."

CFTR is part of a family of thousands of active transporter proteins called ABC proteins. Although CFTR may share many structural features with its ABC "cousins," as Hwang calls them, it has been unclear as to whether CFTR and its cousins may work in a similar manner.

The new idea of how the CFTR utilizes ATP to carry out its function may bear a broader implication because of the evolutionary relationship between CFTR and other ABC transporter proteins. It opens up a wide variety of therapeutic possibilities for other common diseases, such as cancer, heart disease and diabetes, Hwang said, since many other ABC proteins play critical roles in those human illnesses.

"It's taken years for scientists to solve this particular puzzle about the CFTR protein," Hwang said. "Our recent study provides evidence that these ABC transporter proteins and CFTR, a chloride channel, are two peas in a pod. Mother nature employs the same structural framework with just a little bit of modification to do two totally different things. From a basic science perspective, it's a big deal.".....

Ref : http://www.pnas.org/content/110/11/4404.abstract?sid=3e58deab-1076-4255-b20b-73ff47495950

Discovery could increase efficacy of promising cystic fibrosis drug

Pain reliever shows anti-viral activity against flu

In continuation of my update on naproxen

New influenza vaccines must be developed annually, because the surface proteins they target mutate rapidly, the way cars used to get a whole new look every year. The researchers, led by Anny Slama-Schwok of the Institut National de la Recherche Agronomique, Jouy en Josas, France, found a much more stable, reliable target for anti-influenza activity. The so-called ribonucleoprotein complexes are necessary for replication, and the researchers realized they could target the nucleoprotein, preventing assembly of the complexes. Because of its vital function, the nucleoprotein is highly conserved, making it a good potential target for antiviral drugs.

The nucleoprotein's three dimensional structure, solved in 2006, provided the basis for searching for new drugs that could interfere with its action. The researchers did a virtual screening within the Sigma-Aldrich online catalog of biochemicals. That screening identified Naproxen, better known as the over-the-counter pain reliever Aleve, and as expected, it bound to the nucleoprotein, and impeded RNA binding, says Slama-Schwok. In further testing, it reduced the viral load in cells infected with H1N1 and H3N2 influenza A virus, and in mice it demonstrated a therapeutic index against influenza A that was superior to that of any other anti-inflammatory drug.

Specifically, naproxen blocks the RNA binding groove of the nucleoprotein, preventing formation of the ribonucleoprotein complex, thus taking the vital nucleoproteins out of circulation. The researchers write that naproxen is a lead compound for drug development that could be improved by tweaking the molecule to boost its ability to bind to nucleoprotein.

As an already approved drug, naproxen could become a treatment against influenza relatively quickly, the researchers write. Its status as a non-steroidal anti-inflammatory drug (NSAID), which inhibits the COX-2 pathway, as well as an antiviral would boost its efficacy.

Ref : http://aac.asm.org/content/early/2013/02/26/AAC.02335-12.abstract?sid=e3391873-6ffe-4f2e-8737-685e5f2ca15f

Pain reliever shows anti-viral activity against flu