Alkermes Adds Multiple Sclerosis Pill To Expanding Pipeline

Alkermes Adds Multiple Sclerosis Pill To Expanding PipelineTheStreet.comThe company expects to seek permission from FDA to begin human testing of its MMF prodrugs for multiple sclerosis in 2014, with a phase I study slated to begin mid-year. Composition of matter patents have been filed, which if granted, would give the ...

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http://www.thestreet.com/story/11981784/1/alkermes-adds-multiple-sclerosis-pill-to-expanding-pipeline.html?cm_ven=GOOGLEN

Santarus Completes Patient Enrollment in CONTRIBUTE Study with UCERIS (budesonide) as Add-on Treatment to 5-ASA Drugs

Santarus Completes Patient Enrollment in CONTRIBUTE Study with UCERIS ...MarketWatchA Biologics License Application for RUCONEST for the treatment of acute angioedema attacks in patients with hereditary angioedema is under review by the U.S. Food and Drug Administration with a response expected in April 2014. Santarus is also ...

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http://www.marketwatch.com/story/santarus-completes-patient-enrollment-in-contribute-study-with-uceris-budesonide-as-add-on-treatment-to-5-asa-drugs-2013-07-18

SAN DIEGO, Jul 18, 2013 (BUSINESS WIRE) -- Santarus, Inc. /quotes/zigman/91852/quotes/nls/snts SNTS -0.61% today announced the completion of enrollment in the CONTRIBUTE clinical study designed to evaluate the incremental benefit of adding UCERIS(R) (budesonide) extended release 9 mg tablets to oral aminosalicylate (5-ASA) therapy for the induction of clinical remission in adult patients with active, mild to moderate ulcerative colitis. UCERIS is currently approved in the U.S. for the induction of remission in patients with active, mild to moderate ulcerative colitis.

Traditional Chinese medicine - chemistry and application

Traditional Chinese medicine - chemistry and application

Amongst the many aspects of modern Chinese chemistry described in the Journal of Chemical Research during 2012, are phytochemical investigations into the constituents of traditional Chinese medicines derived from plants and fungi. Such studies have afforded new medicines to treat diseases such as Alzheimer’s, malaria and cancer.

http://www.sciencereviews2000.co.uk/blog/view/journal-of-chemical-research/58/traditional-chinese-medicine-chemistry-and-application/671

Top Selling Schizophrenia Drug Abilify (Aripiprazole)

 

Aripiprazole (brand names: Abilify, Aripiprex, OPC-14597,) is an atypical antipsychotic drug with the chemical name 7-[4-(2,3-dichlorophenyl)-1-piperazinyl]-butyloxy]-3,4-dihydro-2(1H)-quinolinone. It was first discovered by the Otsuka Pharmaceutical Company, Ltd., based in Japan, and in collaboration with Bristol-Myers Squibb began to market the drug in the United States following the approval by the Food and Drug Administration for schizophrenia in November 2002. According to IMS Health, Abilify was the fourth top-selling drug in the United States in 2011, with sales of $5.2 billion.

Chemical Structure of Aripiprazole (brand names: Abilify)

Chemical Synthesis of Aripiprazole(active ingredient for Abilify)

Experimental Procedures for the preparation of Aripiprazole (Abilify)

US 5,006,528 discloses process for the preparation of Aripiprazole in two steps. The first step comprises synthesis of 7-(4-bromobutoxy)-3,4-dihydrocarbostyril (7-BBQ) by alkylating the hydroxy group of 7-hydroxy-3,4-dihydrocarbostyril (7-HQ) with 1 ,4-dibromobutane using potassium carbonate in water at reflux temperature for 3 hours to obtain 7-BBQ in 68% yield. The resulting 7-BBQ is further reacted with 1- (2,3-dichlorophenyl)-piperazine to obtain Aripiprazole.

Preparation of 7-(4-bromobutoxy)-3,4-dihydro-2(1H)quinolinone (7-(4-bromobutoxy)-3,4-dihydrocarbostyril; 7-BBQ)

7-Hydroxy-3,4-dihydro-2(1H)-quinolinone (aka 7-Hydroxy-3,4-dihydrocarbostyril, 60gm) and potassium carbonate (76.3 gm) were taken in acetonitrile (1200ml) at room temperature. To this tetra butyl ammonium iodide (13.7 gm) and 1 ,4-dibromobutane (238.5gm) were added and heated at 40- 45°C for 24 hours. Reaction mass was cooled upto room temperature and was filtered off. The resulting filtrate was distilled off under vacuum. The resultant mass was cooled to 25-30°C and cyclohexane (300 ml) was added under stirring. The resulting solid was filtered off and was dried. The resulting solid was taken in water and was stirred for few minutes. The solid was filtered and dried under vacuum at 55-60°C for 20 hours to obtain title compound. mp 110.5-111 °C; 1H NMR (DMSO-d6) ä 1.81 (2H, m, -CH2-), 1.95 (2H, m, -CH2-), 2.41 (2H, t, J ) 7 Hz, -CH2CO-), 2.78 (2H, t, J) 7 Hz, -CH2-C-CO-), 3.60 (2H, t, J ) 6 Hz, -CH2Br), 3.93 (2H,t, J ) 6 Hz, O-CH2-), 6.43 (1H, d, J ) 2.5 Hz), 6.49 (1H, dd, J) 2.5, 8 Hz), 7.04 (1H, d, J ) 8 Hz), 9.98 (1H, s, NHCO). Anal. (C13H16NO2Br) C, H, N.

Yield: 73-75%; Purity: 93-95%

Preparation of Aripiprazole (7-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one)

7-(4-Bromobutoxy)-l ,2,3,4-tetrahydroquinolin-2-one (50 gm) was taken in acetonitrile (500 ml) at 25-30°C. To this potassium carbonate (67.2 gm) and l-(2,3- dichlorophenyl) piperazine hydrochloride (44.9gm) were added under stirring. The reaction mixture was refluxed at 80-85°C for 8 hours. The reaction mass was cooled to room temperature, filtered and the resulting solid was washed with acetonitrile. To the resulting solid, water was added and was stirred. The solid was filtered off, washed with water and dried under vacuum at 75-80°C for 15 hrs. The resulting crude aripiprazole was crystallized from isopropyl alcohol and water to obtain title compound. Yield: 75-80%; Dimer Impurity: <0.1%. 1H NMR: DMSO-d6 d 9.96 [1H, s, NH]; 7.29 [2H, m, Ar]; 7.13 [1H, q, Ar]; 7.04 [1H, d, Ar]; 6.49 [1H, dd, Ar]; 6.45 [1H, d, Ar]; 3.92 [2H, t, -CH2-O-]; 2.97 [4H, bb,2(-CH2-)]; 2.78 [2H, t, -CH2-N2-)]; 2.39 [4H, m, 2(-CH2-)]; 1.73 [2H, m, - CH2-]; 1.58 [2H, m, -CH2-]. IR:cm-1 3193; 2939; 2804; 1680; 1627; 1579; 1520; 1449; 1375; 1270; 1245; 1192; 1169; 1045; 965; 649; 869; 780; 712; 588.

Preparation of aripiprazole anhydrous Type I using isopropyl alcohol and water

Crude aripiprazole (30 g) was taken in isopropyl alcohol (600 ml) and was heated to 80-85°C. Water (90 ml) was added at the same temperature. Activated carbon was added and the mixture was stirred for 30 minutes at the same temperature. The resulting hot solution was filtered and the bed was washed with hot isopropyl alcohol. The resulting filtrate was cooled to 25-30°C for 4 hours. The resulting solid was filtered, washed with isopropyl alcohol and dried under suction for 1 hour. The resulting wet solid was dried in preheated oven maintained at 100-105°C for 6 hours to obtain title compound.

Yield: 87-89% HPLC Purity: 99.89

Anhydrous crystal D: Below detectable limit (BDL) at limit of detection 1%.

Hydrate A: Below detectable limit (BDL) at limit of detection 1 %.

Particle size distribution: d₁₀=15.83 m, d₅₀=60.12 m, d₉₀=144.99 m

Preparation of aripiprazole anhydrous Type I using ethanol and water

Crude aripiprazole (15 g) was taken in ethanol (300 ml) and water (45 ml) and was heated to 80-85°C for 1-2 hours. The resulting mixture was cooled to 25-30°C within 4 hours and stirred for 3 hours. The resulting solid was filtered and dried under suction for 1 hour. The resulting wet solid was dried in preheated oven maintained at 100-105°C for 3 hours to obtain title compound. Yield: 90% HPLC Purity: 99.9%

Anhydrous crystal D: Below detectable limit (BDL) at limit of detection 1%.

Hydrate A: Below detectable limit (BDL) at limit of detection 1%.

Particle size distribution: d₁₀=22.01 m, d₅₀=105.10 m, d₉₀=232.97 m

References For the Process of Aripiprazole (Abilify,)

Yasuo Oshiro, Seiji Sato, Nobuyuki Kurahashi, Tatsuyoshi Tanaka, Tetsuro Kikuchi, Katsura Tottori, Yasufumi Uwahodo, and Takao Nishi; Novel Antipsychotic Agents with Dopamine Autoreceptor Agonist Properties: Synthesis and Pharmacology of 7-[4-(4-Phenyl-1-piperazinyl)butoxy]- 3,4-dihydro-2(1H)-quinolinone Derivatives; J. Med. Chem. 1998, 41, 658-667

Yasuo Oshiro, Seiji Sato, Nobuyuki Kurahashi; Carbostyril derivatives, Otsuka Pharmaceutical Co., Ltd; US patent 5006528;Issue date: Apr 9, 1991

BANDO, Takuji, YANO, Katsuhiko, FUKANA, Makoto, AOKI, Satoshi ;Method for producing fine particles of aripiprazole anhydride crystals b; OTSUKA PHARMACEUTICAL CO., LTD., WO 2013002420 A1

ZHENG Siji, LIU Xiaoyi, FU Linyong, TAN Bo, ZHOU Min: ARIPIPRAZOLE MEDICAMENT FORMULATION AND PREPARATION METHOD THEREFOR. / FORMULATION DE MÉDICAMENT ARIPIPRAZOLE ET SON PROCÉDÉ DE PRÉPARATION. / SHANGHAI ZHONGXI PHARMACEUTICAL January 2013: WO 2013/000391

CN 201210235157

CN102846543A

CN102850268A;

CN101781246A 

GUPTA, Vijay Shankar, KUMAR, Pramod, VIR, Dharam ;Process for producing aripiprazole in anhydrous type i crystals;JUBILANT LIFE SCIENCES LIMITED;WO 2012131451 A1

SRIVASTAVA JAYANT GUPTA Vijay Shankar;Improved process for the preparation of 7.(4-bromobutoxy) 3,4-dihydrocarbostyril, a precursor of aripiprazole;wo2011030213 A1

No Generic Abilify in the US until April 2015

On May 7, 2012, The U.S. Court of Appeals for the Federal Circuit ruled in favor of Otsuka Pharmaceutical Co., Ltd. in its patent litigation against several companies including Israel-based Teva and Weston, Ontario-based Apotex seeking FDA approval to market generic copies of Abilify®. (see the pdf file for the decision upholding the Otsuka patent here). The Federal Circuit affirmed a decision of the U.S. District Court for the District of New Jersey holding that the asserted claims of U.S. Patent No. 5,006,528 (pdf file here) covering aripiprazole, the active ingredient in Abilify®, are valid, thus maintaining patent and regulatory protection for Abilify® in the U.S. until at least April 20, 2015. The case is Otsuka Pharma Co. v. Sandoz Inc., 2011-1126 and 2011-1127, U.S. Court of Appeals for the Federal Circuit (Washington). The lower court case is Otsuka Pharmaceutical Co. v. Sandoz Inc., 07cv1000, U.S. District Court for the District of New Jersey (Trenton).

Chemical Name for Aripiprazole(active ingredient for Abilify): 7-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one
CAS number 129722-12-9

Aripiprazole  brand names: Abilify, Aripiprex) is a partial dopamine agonist of the second generation class of atypical antipsychotics with additional antidepressant properties that is primarily used in the treatment ofschizophrenia, bipolar disorder, major depressive disorder, and irritability associated with autism.^[1] It was approved by the U.S.Food and Drug Administration (FDA) for schizophrenia on November 15, 2002 and the European Medicines Agency on 4 June 2004; for acute manic and mixed episodes associated with bipolar disorder on October 1, 2004; as an adjunct for major depressive disorder on November 20, 2007;^[2] and to treat irritability in children with autism on 20 November 2009.^[3] Aripiprazole was developed by Otsuka in Japan, and in the United States, Otsuka America markets it jointly with Bristol-Myers Squibb.

Aripiprazole can be synthesized beginning with a dichloroaniline and bis(2-chloroethyl)amine:

1.  U.S. Patent 5,006,528

Furiex Pharmaceuticals Announces Completion of Patient Enrollment for Its Phase III Clinical Trials of Eluxadoline for IBS-d

http://www.ama-assn.org/resources/doc/usan/eluxadoline.pdf  
get the structure of eluxadoline here
 name
 Benzoic acid, 5-[[[(2S)-2-amino-3-[4-(aminocarbonyl)-2,6-dimethylphenyl]-1-
oxopropyl][(1S)-1-(5-phenyl-1H-imidazol-2-yl)ethyl]amino]methyl]-2-methoxy-

MOLECULAR FORMULA C32H35N5O5
MOLECULAR WEIGHT 569.7
TRADEMARK None as yet
SPONSOR Furiex Pharmaceuticals, Inc.
CODE DESIGNATIONS JNJ-27018966
CAS REGISTRY NUMBER 864821-90-9
WHO NUMBER 9749

Eluxadoline nonproprietary drug name - AMA

www.ama-assn.org/resources/doc/usan/eluxadoline.pdf‎

• 
  
• 
  

November 28, 2012. N11/133. STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL. USAN (ZZ-82). ELUXADOLINE.

Furiex Pharmaceuticals Announces Completion of Patient Enrollment for Its Phase III Clinical Trials of Eluxadoline for IBS-d

Furiex Pharmaceuticals Inc.Posted on:15 Jul 13

• 
  

Furiex Pharmaceuticals Inc. (NASDAQ: FURX) today announced completion of patient enrollment in the company’s two ongoing Phase III clinical trials studying eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome or IBS-d. Both studies met their target enrollments and Furiex expects to release top line results in the first quarter of 2014.
The two Phase III trials have the same overall design and efficacy endpoints but differ in overall duration. One study has a 52-week treatment period and the other a 30-week treatment period. Each study has three treatment arms placebo 75 mg eluxadoline twice a day and 100 mg eluxadoline twice a day with approximately 375 patients per arm and is designed to capture both the U.S. Food

read all at
http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=76787#.UeUl4EHDBZg

need phase 2 data see here
 In a phase 2 study of the mixed μ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D. ClinicalTrials.gov number, NCT01130272

Research in HIV therapies -A review- The global community has made significant strides forward in its mission to eradicate the HIV epidemic

 

Over the last 30 years, the face of human immunodeficiency virus (HIV) has changed from one largely associated with homosexuality, drug addicts, prejudice, fear and rejection without much hope of a future, to one involving innocent children born of mothers living with HIV for whom it is hoped the disease will be curable and even eradicated. 

According to the World Health Organization (WHO) and UNAIDS, 34 million people were living with HIV worldwide in 2011. Sub-Saharan Africa was, and still is, the most severely affected area. Approximately 5 per cent of adults in this region live with HIV, representing almost 70 per cent of the global HIV-infected population. On a positive note, the number of newly infected people has declined by approximately 25 per cent over the past ten years and, importantly, over the past two years, half of the reductions in HIV infections has been in children.

Treatment and prevention
The approach to, and success of, HIV treatment and prevention has.....................cont

read all at

 http://www.pmlive.com/pharma_news/research_in_hiv_therapies_488697
THE NAMES OF DRUGS USED ARE LISTED HERE, PLEASE READ IT

 

 article by
Wendy McNeely

Adis International (Springer Healthcare), using data derived from Adis R&D Insight and Clinical Trials Insight. For further information on Adis services, please contact Daniela Ranzani on +39 02 423 4562 or email her Daniela.Ranzani@springer.com

PROSTRATE CANCER

ALLOW SLIDESHARE TO LOAD...........................

Prostate cancer from morwenna2

Vical's Allovectin Phase III Trial Results: Consider The Possibilities

Vical's Allovectin Phase III Trial Results: Consider The Possibilities ... Cohen: We saw that happen last year when JNJ prematurely unblinded the pre- chemo Phase III study for the prostate cancer drug Zytiga. The trial achieved ... http://seekingalpha.com/article/1538852-vical-s-allovectin-phase-iii-trial-results-consider-the-possibilities Allovectin-7 is a substance that is being studied as a gene therapy agent in the treatment of cancer, such as malignant melanoma. It is a plasmid/lipid complex containing the DNA sequences encoding HLA-B7 and ß2 microglobulin - two components of major histocompatibility complex (MHC, class I). It increases the ability of the immune system to recognize cancer cells and kill them. In 1999, FDA granted Allovectin-7 orphan drug designation for the treatment of invasive and metastatic melanoma. Allovectin-7 entry in the public domain NCI Dictionary of Cancer Terms

Ohr Pharmaceutical Achieves 50% Enrollment Milestone in Squalamine Eye Drop Phase II Clinical Trial

squalamine

July 10, 2013 /
Ohr Pharmaceutical, Inc. , a pharmaceutical company focused on the development of novel therapeutics for large unmet medical needs, today announced that it has enrolled the first 60 patients in the Company's ongoing OHR-002 Phase II clinical trial evaluating Squalamine Eye Drops for the treatment of the wet form of age-related macular degeneration ("wet-AMD").
The study is a randomized, double blind, placebo controlled study enrolling patients at more than twenty clinical sites in the U.S. "We are excited to have reached the halfway point in the enrollment of our Squalamine Eye Drop study," said Dr. Irach B. Taraporewala, CEO of Ohr.
"This milestone sets the stage for the planned interim analysis once the 60 patients complete the nine month treatment protocol, and we expect the data to be available in the second quarter of 2014.
" "I am pleased with the continued progress in the trial to evaluate Squalamine Eye Drops for exudative AMD," commented Dr. Jason Slakter, retinal disease specialist at Vitreous-Retina-Macula Consultants of NY, and member of Ohr's scientific advisory board. "The Company's eye drop for treating wet-AMD would potentially offer patients a convenient, self-administered, treatment alternative or adjunct to currently used intravitreal injections directly into the eye. This could be a significant advancement in the future treatment of wet-AMD." Study OHR-002 is a randomized, double blind, placebo controlled Phase II study to evaluate the efficacy and safety of Squalamine Eye Drops for the treatment of wet-AMD.
The study will enroll 120 treatment naive wet-AMD patients at more than twenty clinical sites in the U.S., who will be treated with Squalamine Eye Drops or placebo eye drops twice daily for a nine month period.
The primary and secondary endpoints include visual acuity parameters, need for rescue intravitreal injections, and safety. The protocol includes an interim analysis upon the completion of the treatment period in 50% of the patients (60). More information on the clinical trial can be found at clinicaltrials.gov. About Ohr Pharmaceutical, Inc. Ohr Pharmaceutical, Inc. (NasdaqCM:OHRP) is a pharmaceutical company dedicated to the clinical development of new drugs for underserved therapeutic needs in large and growing markets. The Company is focused on advancing its pipeline products currently in phase II clinical development: Squalamine Eye Drops for the treatment of the wet form of age-related macular degeneration, and OHR/AVR118 for the treatment of cancer cachexia. Additional information on the Company can be found at www.ohrpharmaceutical.com.

Women at High Breast Cancer Risk Should Consider Preventive Drugs: Experts

July 9, 2013 -- Women at high risk of breast cancer should discuss with their doctors the use of so-called chemopreventive drugs to reduce that risk, according to a new practice guideline issued by the American Society of Clinical Oncology (ASCO).
The new guideline updates the previous one, issued in 2009, said Dr. Kala Visvanathan, director of the clinical cancer genetics and prevention service at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, who co-chaired the guidelines panel.

Read more at 

http://www.drugs.com/news/women-breast-cancer-risk-should-consider-preventive-experts-45805.html

Cancer Fighting Fish: Source of New Drugs?

 During the process known as metastasis, cancer cells detach from the bulk of the tumor and colonize distant organs. In order to do so, they enter the blood circulation by attaching to the cells that constitute tumor vessels. This event is driven by interactions occurring between Galβ1–3GalNAcα1-Ser/Thr, a disaccharide present on the surface of tumor cells, and galectin-3, a protein situated on vascular cells.

 http://www.chemistryviews.org/details/news/4540321/Cancer_Fighting_Fish_Source_of_New_Drugs.html

• Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostatecancer metastasis,
  P. Guha, E. Kaptan, G. Bandyopadhyaya, S. Kaczanowska, E. Davila, K. Thompson, S. S. Martin, D. V. Kalvakolanu, G. R. Vasta, H. Ahmed,
  Proc. Natl. Acad. Sci. USA 2013.
  DOI: 10.1073/PNAS.1202653110

Garlic in India

 

 

Garlic in India

The ancient Indians had varying views on garlic; but, for the most part, it was considered to be highly beneficial to the body. Ancient Sanskrit writings, dating as far back as 5,000 years ago, described the healing properties of garlic. In fact, the ancient medical practice of Ayurveda, which is still practised today, promoted garlic as one of the most important herbs. It recommends garlic in over 100 formulations for treating stomach, liver, tumor, asthma and other similar problems.

The Charaka Samhita is the oldest surviving Ayurvedic text, dating back to 200 BCE to 200 CE (AD), and suggests using garlic for alleviating:

• worms
• piles
• leukoderma
• leprosy
• epilepsy
• heart disease
• fainting
• arthritis
• rheumatism
• chronic rhinitis
• baldness.

 It was also included in the diet of nursing mothers to encourage milk secretion in nursing mothers and was hung to protect against evil spirits.

Other Ayurvedic teachings recommend garlic for:

• arteriosclerosis
• pain
• cholera
• dysentery
• indigestion
• constipation
• appetite loss
• fatigue
• typhoid
• tuberculosis
• cough
• fractures. 

It is also advocated for improving eyesight, intelligence, sexual debility, and impotency.

On the other hand, the ancient Indians believed garlic was a natural aphrodisiac that inspired lust and stimulated passions and, as a result, holy men, monks, widows, adolescents, and fasting persons were forbidden from consuming garlic. In addition, it was considered to be rajasic food; which meant it had unsettling effects on the body and devotees on the path to spiritual enlightenment were advised against eating it. The Buddists, Jains, Greeks and Romans also shared these sentiments; however, some believe the mild irritation garlic caused in the genitourinary tract may have resulted in its aphrodisiac and rajasic status.

References:

1. Charaka Samhita (Handbook on Ayurveda), edited by G. Van Loon (2002)

Chocolate as medicine: a quest over the centuries

The rehabilitation of chocolate has occurred only in recent times. The pages of scientific magazines have been positively recaptured and chocolate’s reputation is being restored to the value that Carl Linnaeus credited to this food, when he named the generous plant Theobroma cacao, the food of the gods
read all at
http://www.rsc.org/chemistryworld/2013/07/chocolate-medicine-wilson-hurst

Verona Pharma Plc Peer-Reviewed Paper Suggests RPL554 With Glycopyrrolate, Or Other Muscarinic Receptor Antagonists, Produces Synergistic Bronchodilation

RPL554

Verona Pharma Plc ("Verona Pharma" Or The "Company") Peer-Reviewed ...

Wall Street Journal
Verona Pharma is developing first-in-class drugs to treat respiratory disease, such as COPD, asthma and chronic, severe cough. The Company has three drug programmes, two of which are in Phase II. The lead programme, RPL554, is an innovative dual ...
read all at
http://online.wsj.com/article/PR-CO-20130701-900428.html?mod=googlenews_wsj



RPL-554 (LS-193,855) is a drug which acts as a long-acting inhibitor of the phosphodiesterase enzymes PDE-3 and PDE-4, producing both bronchodilator and antiinflammatory effects.^[1] It is being developed by Verona Pharma as a potential treatment for asthma and hay fever, and is currently in clinical trials.^[2][3]

1.  Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP. The Pharmacology of Two Novel Long-Acting Phosphodiesterase 3/4 Inhibitors, RPL554 (9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl) -3,4,6,7-tetrahydro-2H-pyrimido(6,1-a)isoquinolin-4-one) and RPL565 (6,7-Dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido(6,1-a)isoquinolin-4-one). Journal of Pharmacology and Experimental Therapeutics 2006; 318(2):840-848.
2.  Verona Pharma Plc - Lead Drug RPL554
3.  Asthma and hay fever drug tested. BBC News, Wednesday 10 September 2008

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