Showing posts with label herbs. Show all posts
Showing posts with label herbs. Show all posts

Wednesday, 24 July 2013

Isis Phase II drug APOIIIRx slashes triglycerides by 64%

Isis Pharmaceuticals is "very encouraged" by a second set of mid-stage data for its heart drugAPOIIIRx, which shows that it can substantially slash levels of dangerous fats in the blood. 

In a 26-patient Phase II trial, patients with severely high levels of triglycerides taking Isis' drug alongside fibrates experienced 64% drop in triglycerides, and a 70% drop in apolipoprotein C-III (apoC-III), a component of 'bad' low-density lipoprotein
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Tuesday, 23 July 2013

New therapy for pancreatic cancer: Phase III clinical trial currently recruiting Australian patients

Currently there is a clinical trial that is recruiting patients from around the globe including sites across Australia. The trial is testing MM-398; a therapy that uses the latest in nanotechnology to deliver the chemotherapeutic agent irinotecan encased in a liposome to cancer patients.1 In particular this trial, named NAPOLI-1 (NAnoliPOsomaL Irinotecan) is recruiting patients with pancreatic cancer who have previously been treated with the chemotherapy agent gemcitabine unsuccessfully i.e. their disease has gone on to spread/progress despite this treatment.2,3
read all here


Irinotecan (Camptosar, Pfizer; Campto, Yakult Honsha) is a drug used for the treatment of cancer.
Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1. In chemical terms, it is a semisynthetic analogue of the natural alkaloid camptothecin.
Its main use is in colon cancer, in particular, in combination with other chemotherapy agents. This includes the regimen FOLFIRI, which consists of infusional 5-fluorouracil,leucovorin, and irinotecan.
Irinotecan received accelerated approval by the U.S. Food and Drug Administration (FDA) in 1996 and full approval in 1998. During development, it was known as CPT-11.
Irinotecan is activated by hydrolysis to SN-38, an inhibitor of topoisomerase I. This is then inactivated by glucuronidation by uridine diphosphate glucoronosyltransferase 1A1 (UGT1A1). The inhibition of topoisomerase I by the active metabolite SN-38 eventually leads to inhibition of both DNA replication and transcription.

Merrimack currently has six oncology therapeutics in clinical development, multiple product candidates in preclinical development and an active Systems Biology-driven discovery effort. 
  • Indication:
  • Description:
  • Target
  • Pancreatic Cancer (2nd line, 2 indications), Colorectal Cancer, Glioma
  • Nanotherapeutic
  • Encapsulated irinotecan
MM-398 is a nanotherapeutic consisting of the chemotherapuetic irinotecan, encapsulated in a liposomal sphere. MM-398 is designed to rely on the natural blood flow of the tumor to direct the therapy directly to the site of the cancer and minimize exposure to non-target cells.
MM-398 in the Clinic
MM-398 is being evaluated in clinical trials for its ability to treat tumors resistant to chemotherapy across multiple types of cancers, including pancreatic, lung, colorectal and glioma. The FDA and the European Medicines Agency granted MM-398 orphan drug designation in 2011 for the treatment of patients with metastatic pancreatic cancer who have previously failed treatment with the chemotherapy drug gemcitabine. Our Phase 3 study, NAPOLI-1 (NAnoliPOsomaL Irinotecan), is currently underway.

Phase III prostate cancer trial for 'homing' injection shows improvements

Prostate cancer

Phase III prostate cancer trial for 'homing' injection shows improvements
A new treatment for advanced prostate cancer that homes-in on tumours to deliver a high-energy burst of radiation to cancer cells has shown significant benefits in a large scale clinical trial.
The trial of 921 patients showed that treatment with the radioactive Radium-223 gave men with late-stage prostate cancer an average extra of 15 weeks of life.

Tuesday, 16 July 2013

Top Selling Schizophrenia Drug Abilify (Aripiprazole)


Abilify-Aripirazole-Atypical Antipsychotics-Otsuka-BMS
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 Strutcure of Aripirazole-Abilify-Antipsychotics-Otsuka-BMS-阿立哌唑-安律凡-大冢制药-エビリファイ
Chemical Synthesis of Aripiprazole(active ingredient for Abilify)
Chemical Synthesis of Abilify-Aripirazole-Atypical Antipsychotics-Otsuka-BMS-阿立哌唑-アリピプラゾール
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 DerivativesJ. 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
CN 201210235157
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: AbilifyAripiprex) is a partial dopamine agonist of the second generation class of atypical antipsychotics with additional antidepressant properties that is primarily used in the treatment ofschizophreniabipolar disordermajor 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 StatesOtsuka 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
Aripiprazole synth.png

Monday, 15 July 2013

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

HIV therapies 
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
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 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

Friday, 12 July 2013

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 ...

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

Monday, 1 July 2013

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


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 ...

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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

Friday, 28 June 2013

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 ...

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.

Tuesday, 25 June 2013

How many modes of action should an antibiotic have?

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?

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

thank you animated gif photo: Thank You w thumb up ty02.gif

Friday, 21 June 2013

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

File:Mannitol structure.png
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.