Novartis' Omalizumab Meets Phase III Endpoints

Novartis' Omalizumab Meets Phase II...

Novartis reports new Phase III data showing omalizumab significantly...



http://www.pharmalive.com/novartis-omalizumab-meets-phase-iii-endpoints

Structures of resistance-breaking derivatives of established antibiotic classes. Selected compounds are depicted that were recently launched or are currently in development. Ceftobiprole has increased affinity for PBP2a, a member of the target family of penicillin-binding proteins not affected by marketed β-lactams. Tigecycline, iclaprim, telithromycin, and telavancin make contacts to additional binding sites on their established targets or address additional targets. Structural elements responsible for the novel target interactions are marked bold. MCB-3681, TD-1792, and CBR-2092 are hybrid molecules, in which two pharmacophors from different antibiotic classes are attached by linkers. Linkers are marked bold

All antibiotics that have been successfully employed for decades as monotherapeutics in the treatment of bacterial infections rely on mechanisms of bacterial growth inhibition which are by far more complex than inhibition of a single enzyme. Such successful antibiotics have in common that they address several targets in parallel and/or that their targets are encoded by multiple genes. Such multiplicity of targets and of target genes has the advantage that the emergence of spontaneous target-related resistance is a comparatively slow process. Recently registered antibiotics and novel antibiotics in development are discussed in the light of this promising concept of antibacterial polypharmacology.

How many modes of action should an antibiotic have?

• Heike Brötz-Oesterhelt 
• Nina A Brunner 

• AiCuris GmbH & Co.KG, Friedrich-Ebert Strasse 475, Building 302, D-42117 Wuppertal, Germany

Available online 30 July 2008

• http://dx.doi.org/10.1016/j.coph.2008.06.008,

http://www.sciencedirect.com/science/article/pii/S1471489208000799

Preventing Dangerous Liaisons

A new peptidomimetic inhibits prostate cancer’s growth by preventing the androgen receptor from binding to its cofactor
Read more

http://www.chemistryviews.org/details/news/4884471/Preventing_Dangerous_Liaisons.html

Gut Feeling for Obesity Treatment

Gut Feeling for Obesity Treatment

Newly synthesized benzimidazole-type compounds work directly in the gut rather than circulating in the blood to lower triglycerides
Read more

http://www.chemistryviews.org/details/news/4907951/Gut_Feeling_for_Obesity_Treatment.html

Silibinin (INN), also known as silybin, is the major active constituent of silymarin, a standardized extract of the milk thistle seeds containing mixture of flavonolignans consisting of among others of silibinin, isosilibinin, silicristin, and silidianin

Silibinin (INN), also known as silybin, is the major active constituent of silymarin, a standardized extract of the milk thistle seeds containing mixture of flavonolignans consisting of among others of silibinin, isosilibinin, silicristin, and silidianin. Silibinin itself is mixture of two diastereomers silibinin A and silybinin B in approximately equimolar ratio. Both in vitro and animal research suggest that silibinin has hepatoprotective (antihepatotoxic) properties that protect liver cells against toxins.^[1][2] Silibinin has also demonstrated in vitro anti-cancer effects against human prostate adenocarcinoma cells, estrogen-dependent and -independent human breast carcinoma cells, human ectocervical carcinoma cells, human colon cancer cells, and both small and nonsmall human lung carcinoma cells.^[3][4][5][6]
Chemically modified silibinin, silibinin dihydrogen disuccinate disodium (trade name Legalon SIL) a solution for injection, is currently being tested as a treatment of severe intoxications with hepatotoxic substances, such as death cap (Amanita phalloides) poisoning.^[7] There is also clinical evidence for the use of silibinin as a supportive element in alcoholic and Child grade ‘A’ liver cirrhosis.^[8]

 FROM SILYBUM MARIANUM (L.) GAERTN.
A NEW NATURAL PREVENTIVE TARGETED AT THE LIVER
The liver, due to the vital role it plays in metabolism, is particularly exposed to the harmful action of endogenous and exogenous toxic substances. In fact, many potentially harmful molecules (alcohol, drugs, hormones, etc.) are metabolized by the liver and transformed into more hydro-soluble derivatives for subsequent biliary extraction and removal from the body. This detoxication process is achieved by a variety of enzymes (oxidizing, reducing, hydrolyzing or conjugating) located in the hepatic microsomes, part of the smooth endoplasmic reticulum of the liver cell. For this reason the upkeep of the integrity of the liver cell is necessary for the safeguarding of health. Several biochemical reactions involve as starters or intermediates various free radical species which constitute a continuous risk factor for the integrity of the hepatocytes.Therefore, any prevention aimed at reducing potential damage to the liver and any substances contributing to its integrity are certainly of interest. Derivatives of the traditionally used European plant Silybum marianum (L.) Gaertn. (Asteraceae) occupy an eminent position in liver protection. The name Silybum derives from "sillybon" (tuft, pendant), an ancient Greek word used by Dioscorides (I century A.D.) to indicate a thistle with white spotted leaves. An old legend tells that these white marks and stripes on the leaves represent the drops of Mary's milk fallen from her breast while she was breastfeeding Jesus during their escape to Egypt.² Since ancient times S. marianum has been known and used to be recommended as an emetic. During the Middle Ages the plant was probably cultivated in monasteries and used for medicinal purposes: the roots, herb and leaves were recommended for swelling and erysipelas (St. Hildegard from Bingen, 1098-1179) or for the treatment of liver complaints (Lonicerus, John Gerard, Pietro Andrea Mattioli, XVI-XVII centuries). From 1755 onwards, the specific use of S. marianum fruit for the treatment of liver disease, disorders of the bile duct and spleen was documented. At present, the standardized extract (silymarin) obtained from the fruit of S. marianum and containing as main constituents silybin, silydianin and silychristin (Fig.1), is widely used in European medicine in the treatment of liver disease. The main constituent silybin has been subjected to several biochemical and pharmacological studies which have demonstrated its interesting properties but also its poor bioavailability. Complexation with soy phosphatidylcholine gives rise to the lipophilic complex (US Patent 4, 764, 508) which substantially improves the bioavailibility of silybin. This results in a marked preventive action as observed in several models of liver intoxication including those with a strong involvement of oxidative stress. In this way, the silybin-phosphatidylcholine complex SILIPHOS®, containing 33% of silybin, endowed with antioxidant activity and, simultaneously, able to prevent cellular derangement by stabilizing the cell membranes and restoring the normal ultrastructure of the hepatocytes, plays a key role in the prevention of liver damage.http://www.swansonvitamins.com/health-library/products/siliphos.html

1. Al-Anati L, Essid E, Reinehr R, Petzinger E (2009). "Silibinin protects OTA-mediated TNF-alpha release from perfused rat livers and isolated rat Kupffer cells". Molecular Nutrition & Food Research 53 (4): 460–6. doi:10.1002/mnfr.200800110. PMID 19156713.
2. Jayaraj R, Deb U, Bhaskar AS, Prasad GB, Rao PV (2007). "Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in mice". Environmental Toxicology 22 (5): 472–9. doi:10.1002/tox.20283. PMID 17696131.
3. Mokhtari MJ, Motamed N, Shokrgozar MA (2008). "Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line". Cell Biology International 32 (8): 888–92. doi:10.1016/j.cellbi.2008.03.019. PMID 18538589.
4. Bhatia N, Zhao J, Wolf DM, Agarwal R (1999). "Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin". Cancer Letters 147 (1–2): 77–84. doi:10.1016/S0304-3835(99)00276-1. PMID 10660092.
5. Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS (2007). "Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer". Journal of Surgical Research 143 (1): 58–65. doi:10.1016/j.jss.2007.03.080. PMID 17950073.
6. Sharma G, Singh RP, Chan DC, Agarwal R (2003). "Silibinin induces growth inhibition and apoptotic cell death in human lung carcinoma cells". Anticancer Research 23 (3B): 2649–55. PMID 12894553.
7. Mitchell, T (2009). "Intravenous Milk thistle (silibinin-legalon) for hepatic failure induced by amatoxin/Amanita mushroom poisoning". (Clinical study).
8. Saller R, Brignoli R, Melzer J, Meier R (2008). "An updated systematic review with meta-analysis for the clinical evidence of silymarin". Forschende Komplementärmedizin (2006) 15 (1): 9–20. doi:10.1159/000113648. PMID 18334810. Retrieved 2010-12-14.

A combination of the myxoma virus and the immune suppressant rapamycin can kill glioblastoma multiforme, the most common and deadliest malignant brain tumor

 read all at

http://www.dddmag.com/news/2013/06/virotherapy-rapamycin-combo-kills-brain-tumors

rapamycin, sirolimus

.Artificial sweetener a potential treatment for Parkinson’s disease.

Mannitol, a sugar alcohol produced by fungi, bacteria, and algae, is a common component of sugar-free gum and candy. The sweetener is also used in the medical field — it’s approved by the FDA as a diuretic to flush out excess fluids and used during surgery as a substance that opens the blood/brain barrier to ease the passage of other drugs.

Now Profs. Ehud Gazit and Daniel Segal of Tel Aviv University‘s Department of Molecular Microbiology and Biotechnology and the Sagol School of Neuroscience, along with their colleague Dr. Ronit Shaltiel-Karyo and PhD candidate Moran Frenkel-Pinter, have found that mannitol also prevents clumps of the protein α-synuclein from forming in the brain — a process that is characteristic of Parkinson’s disease.

Read more at

http://scienceblog.com/63913/artificial-sweetener-a-potential-treatment-for-parkinsons-disease/

Ambrx partners with Zhejiang for breast cancer antibody drug conjugate development

Ambrx has partnered with Zhejiang Medicine for the development and commercialization of ARX788, its antibody drug conjugate (ADC) for breast cancer... Targeting Her2-positive breast cancer, ARX788 is developed by the clinical stage biopharmaceutical company Ambrx as site-specific ADC.

http://contractresearch.pharmaceutical-business-review.com/news/ambrx-partners-with-zhejiang-for-breast-cancer-antibody-drug-conjugate-development-170613

Chemical Nanoengineering: Designing Drugs Controlled by Light

Researchers at IRB Barcelona and IBEC design the first peptides regulated by light to modulate biological processes. (Credit: Copyright Laura Nevola)





The scientific cooperation between chemists, biotechnologists and physicists from various Catalan institutes, headed by Pau Gorostiza, from the Institute for Bioengineering of Catalonia (IBEC), and Ernest Giralt, from the Institute for Research in Biomedicine (IRB Barcelona), has led to a breakthrough that will favor the development of light-regulated therapeutic molecules.

read all at
 http://www.sciencedaily.com/releases/2013/06/130618101516.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fmatter_energy%2Forganic_
chemistry+%28ScienceDaily%3A+Matter+%26+Energy+News+--+Organic+Chemistry%29

HANDBOOK OF MEDICINAL HERBS-by DOCSTOC

Handbook of Medicinal Herbs (PDF)

Incyte Drug Jakafi ® (ruxolitinib) Improved Overall Survival in Phase III Trial of Patients with Myelofibrosis

ruxolitinib Incyte Drug Jakafi®ruxolitinib Improved Overall Survival in Phase ... Incyte Drug Jakafi®ruxolitinib Improved Overall Survival in Phase III Trial of Patients with Myel. by Business Wirevia The Motley Fool Jun 16th 2013 220AM ... http://www.dailyfinance.com/2013/06/16/incyte-drug-jakafi-ruxolitinib-improved-overall-su/ Ruxolitinib (trade names Jakafi and Jakavi, by Incyte Pharmaceuticals and Novartis) is a drug for the treatment of intermediate or high-risk myelofibrosis, a type of bone marrow cancer. It is also being investigated for the treatment of other types of cancer (such as lymphomas and pancreatic cancer), for polycythemia vera, and for plaque psoriasis. The phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-I (COMFORT-I) and COMFORT-II trials showed significant benefits by reducing spleen size, relieving debilitating symptoms, and improving overall survival

ABILIFY® Granted Additional Approval as Adjunctive Therapy for the Treatment of Depression in Japan

ABILIFY® Granted Additional Approval as Adjunctive Therapy for the Treatment of Depression in Japan

Otsuka Pharmaceutical Co., Ltd. today obtained regulatory approval from the Japanese Ministry of Health, Labor and Welfare (MHLW) for ABILIFY as the first antsipsychotic drug in Japan to treat...

http://japan.pharmaintellect.com/2013/06/abilify-granted-additional-approval-as.html?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+Pharmainvest+%28PharmaInvest%29

Ibrutinib Phase 2 Data: Analyses Show Efficacy with Ibrutinib Monotherapy in Patients with Relapsed or Refractory Mantle Cell or Diffuse Large B-cell Lymphoma

ibrutinib

June 16, 2013 

Janssen Research & Development, LLC (Janssen), today announced the results of two separate Phase 2 studies suggesting that ibrutinib, an investigational oral Bruton's tyrosine kinase (BTK) inhibitor, shows efficacy when used as a monotherapy in patients with relapsed/refractory mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL). The studies were presented today at the European Hematology Association (EHA) 18^th Annual Congress in Stockholm, Sweden. Ibrutinib is being jointly developed by Janssen and Pharmacyclics, Inc.

Ibrutinib (USAN), also known as PCI-32765, is an experimental drug candidate for the treatment of various types of cancer. It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton tyrosine kinase (Btk).

Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson's Janssen Pharmaceutical division for B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and multiple myeloma.

Ibrutinib was first designed and synthesized at Celera Genomics by Zhengying Pan, who along with a team of chemists and biologists reported in 2007 a structure-based approach for creating a series of small molecules that inactivate BTK through covalent binding to cysteine-481 near the ATP binding domain of BTK[2]. 

These small molecules irreversibly inhibited BTK by using a Michael acceptor for binding to the target cysteine. 

In April 2006, Pharmacyclics acquired Celera’s small molecule BTK inhibitor discovery program, which included a compound, PCI-32765 (known as compound 13 in the Pan et al paper) that was subsequently chosen for further preclinical development based on the discovery of anti-lymphoma properties in vivo . 

Since 2006, Pharmacyclics’ scientists have advanced the molecule into clinical trials and identified specific clinical indications for the drug.  It also has potential effects against autoimmune arthritis.

Pharma-Execs-2012-Pipeline-Report

 
Just days before this article went to press, FDA approved the first of a new kind of oral enzyme treatment that mediates cellular response, Incyte/Novartis' Jakafi, for a rare bone marrow disease called myelofibrosis. The next JAK inhibitor, Pfizer's toficitinib, could hit the market late next year, meaning a lot of rheumatoid arthritis patients will never again have to sit in a hospital for a couple of hours to get an anti-TNF infusion. Many innovative drugs, long out of the gate, are closing in on the finish line; science is back, and a better understanding of the way genomics shapes disease is bringing about better outcomes, and sometimes faster approvals.

read all at

http://www.pharmexec.com/pharmexec/Deals/Pharm-Execs-2012-Pipeline-Report/ArticleStandard/Article/detail/752361?contextCategoryId=48159

The Design, Development and Scale-Up of Safe Chemical Processes and Operations

2 - 4 October 2013 • Chilworth Global, Princeton, NJ, USA

Dr Vahid Ebadat, Chilworth Technology Inc.

Dr. Swati Umbrajkar

Dr Will Watson, Scientific Update

http://ecampaign.scientificupdate.co.uk/index.php?action=social&c=17c276c8e723eb46aef576537e9d56d0.882

Developing safe processes is of paramount importance to any chemical company. Exothermic chemical reactions in batch and semi- batch processes can result in serious injury to people and plant if they get out of control. Results of thermal runaways include violent loss of containment, possibly explosion and the release of flammable or toxic materials to the environment.
Employers are bound by Health & Safety legislation to ensure the safety of their employees and those outside their employment who might be affected by their activities. Chemical manufacturers must therefore be aware of all potential dangers in their processes and take steps to eliminate them. The best approach is to design safety into the process from the start.
This seminar is designed to enhance the awareness of chemists and engineers regarding hazard issues. Utilizing the expertise of the chemists and chemical engineers at Chilworth Global and Scientific Update, it will consider hazard control of new chemical processes throughout their development cycle: from early development through to full-scale production. Hazards can often be eliminated by appropriate choice of reagent or synthetic route at the R&D stage. Where this is not possible, techniques exist to quantify the hazards so that robust engineering solutions can he applied in production.

Who Should Attend?

• R&D and Process Development Chemists, Chemical Engineers, Managers and anyone whose responsibilities include safety or risk assessment of chemical processes or building safety into chemical process scale-up.

Visit SCIENTIFIC UPDATE website for complete course information.

http://ecampaign.scientificupdate.co.uk/index.php?action=social&c=17c276c8e723eb46aef576537e9d56d0.882

DRUG SCALEUP AND MANUFACTURING INTERNATIONAL BY DR ANTHONY MELVIN CRASTO, WORLD DRUG TRACKER

http://drug-scaleup-and-manufacturing.webnode.com/news/my-website-on-scaleup-of-organic-compounds/

AstraZeneca buys Pearl Therapeutics in $1.15bn deal

AstraZeneca buys Pearl Therapeutics in $1.15bn deal


The UK's second largest drug company, AstraZeneca, has announced that it will buy US based lung disease drug specialist, Pearl Therapeutics, in a deal worth up to $1.15bn (£742m).

 http://www.pharmaceutical-technology.com/news/newsastrazeneca-buys-pearl-therapeutics-in-115bn-deal?WT.mc_id=DN_News














 

PFIZER, MERCK, SANOFI --Does This Pipeline Promise Tomorrow's Blockbuster Sales?

Does This Pipeline Promise Tomorrow's Blockbuster Sales?

Motley Fool
Pfizer's future looks strong with its robust pipeline that boasts 74 total drugs in development, and at least in late-stage candidates, Merck looks strong as well, with another 23 therapies in phase 2 development. However, it's the quality, not the ...


read all at
http://www.fool.com/investing/general/2013/06/12/does-this-pipeline-promise-tomorrows-blockbuster-s.aspx

Will nanorods be the next big male contraceptive idea?

Will nanorods be the next big male contraceptive idea?

Successful experiments on mice bode well for a future human contraceptive - if men can stomach the injections Researchers in China have discovered a new method of male contraception: a quick injection of gold nanorods into the testes, followed by a 10 minute dose of infrared light. The procedure has only been demonstrated in mice, but the researchers believe it could be used for dogs and cats – and even humans. Pet contraception is considered an important topic, given the four million unwanted dogs and cats that are thought to be put down every year in the US alone. Many vets routinely sterilise pets, but since surgery requires time and expertise scientists have been looking for cheaper, simpler alternatives.

http://www.rsc.org/chemistryworld/2013/06/gold-nanorods-male-contraceptive



Functionalising the nanorods with methoxy poly(ethylene glycol) enables them to be used for contraception or even sterilisation © ACS

90Y-Epratuzumab Study Shows Improvement of Therapy Results Following R-CHOP

 


June 10, 2013 (GLOBE NEWSWIRE) -- Immunomedics, Inc. (Nasdaq:IMMU), a biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases, today reported that adding two doses of epratuzumab labeled with the radioisotope, yttrium-90 (90Y), to a combination of rituximab and CHOP chemotherapy (R-CHOP), the standard of care for patients with diffuse large B-cell lymphoma (DLBCL), appeared to improve elderly patients' responses to treatment.

read all at
http://www.drugs.com/clinical_trials/90y-epratuzumab-study-shows-improvement-therapy-results-following-r-chop-15714.html 




by
WORLD DRUG TRACKER
DR ANTHONY