Alexion’s Soliris® (eculizumab) Receives Orphan Drug Designation for the Treatment of Neuromyelitis Optica (NMO)

Structure of eculizumab. Eculizumab was engineered to reduce immunogenicity and eliminate effector function. Human IgG2 and IgG4 heavy-chain sequences were combined to form a hybrid constant region that is unable to bind Fc receptors or to activate the complement cascade. Eculizumab exhibits high affinity for human C5, effectively blocking its cleavage and downstream proinflammatory and cell lytic properties. Reprinted from Rother et al with permission.  

Alexion's Soliris® (eculizumab) Receives Orphan Drug Designation for the ...

Fort Mills Times
In a Phase 2 study presented at the 2012 annual meeting of the American Neurological Association (ANA), Soliris treatment was associated with a significant reduction in the frequency of relapses (recurring attacks) in patients with severe, relapsing ...

http://www.fortmilltimes.com/2013/06/27/2789656/alexions-soliris-eculizumab-receives.html


Eculizumab (INN and USAN; trade name Soliris) is a humanized monoclonal antibody that is a first-in-class terminal complement inhibitor and the first therapy approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare, progressive, and sometimes life-threatening disease characterized by excessive destruction of red blood cells (hemolysis). It costs £400,000 (US$600,000) per year per patient

Eculizumab also is the first agent approved for the treatment of atypical hemolytic uremic syndrome (aHUS), an ultra-rare genetic disease that causes abnormal blood clots to form in small blood vessels throughout the body, leading to kidney failure, damage to other vital organs and premature death.

In clinical trials in patients with PNH, eculizumab was associated with reductions in chronic hemolysis, thromboembolic events, and transfusion requirements, as well as improvements in PNH symptoms, quality of life, and survival.Clinical trials in patients with aHUS demonstrated inhibition of thrombotic microangiopathy (TMA),the formation of blood clots in small blood vessels throughout the body, including normalization of platelets and lactate dehydrogenase (LDH), as well as maintenance or improvement in renal function.

Eculizumab was discovered and developed by Alexion Pharmaceuticals and is manufactured by Alexion. It was approved by the United States Food and Drug Administration (FDA) on March 16, 2007 for the treatment of PNH, and on September 23, 2011 for the treatment of aHUS. It was approved by the European Medicines Agency for the treatment of PNH on June 20, 2007, and on November 24, 2011 for the treatment of aHUS. Eculizumab is currently being investigated as a potential treatment for other severe, ultra-rare disorders.

Celgene buys MophoSys for myeloma antibody development

Celgene buys MophoSys for myeloma antibody development
German biopharmaceutical company MorphoSys will jointly develop an antibody for the treatment of multiple myeloma (MM) and leukaemia with Celgene Corporation. 

http://www.pharmaceutical-technology.com/news/newscelegene-buys-mophosys-for-myeloma-antibody-development?WT.mc_id=DN_News

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.