ONE LAKH VIEWS ON ALL MY BLOGS--DR ANTHONY CRASTO

DR ANTHONY MELVIN CRASTO Ph.D

WORLDDRUGTRACKER
ANNOUNCING ONE LAKH PLUS VIEWS ON ALL BLOGS- DR ANTHONY CRASTO

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SEE ALSO

• Organic Chemistry by Dr Anthony
• Technology Transfer
• Stereochemistry
• Spectroscopy
• Polymorphism
• Reactions in Org Chem

DR ANTHONY MELVIN CRASTO, Worlddrugtracker, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his PhD from ICT ,1991, Mumbai, India, in Organic chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK- GENERICS LTD, Research centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Prior to joining Glenmark, he worked with major multinationals like Hoechst Marion Roussel, now sSanofi, Searle India ltd, now Rpg lifesciences, etc. he is now helping millions, has million hits on google on all organic chemistry websites. His New Drug Approvals, Green Chemistry International, Eurekamoments in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 25 year tenure, good knowledge of IPM, GMP, Regulatory aspects, he has several international drug patents published worldwide . He gas good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, polymorphism etc He suffered a paralytic stroke in dec 2007 and is bound to a wheelchair, this seems to have injected feul in him to help chemists around the world, he is more active than before and is pushing boundaries, he has one lakh connections on all networking sites, He makes himself available to all, contact him on +91 9323115463, amcrasto@gmail.com

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amcrasto@gmail.com

email me if u like my posts

Primary pulmonary hypertension

Primary pulmonary hypertension from drvasudev007

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
read all at
.http://www.pharmatimes.com/Article/13-07-23/Isis_PhII_drug_slashes_triglycerides_by_64.aspx

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.<sup>2,3
read all here

http://www.virtualmedicalcentre.com/news/new-therapy-for-pancreatic-cancer-phase-iii-clinical-trial-currently-recruiting-australian-patients/18708</sup>


irinotecan

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. 
MM-398
(Nanotherapeutic)

• Indication:
• Description:
• Target

• Pancreatic Cancer (2^nd 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.
posters
http://merrimackpharma.com/library/research/mm-398-preclinical-posters

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

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.http://www.pharmaceutical-technology.com/news/newsphase-iii-prostate-cancer-trial-for-homing-injection-shows-benefit?WT.mc_id=DN_News

Anticancer agent – elacytarabin

Elacytarabine

Cytarabine is a cytosine derivative that is a common component of chemotherapy regimens for blood cancers such as acute myeloid leukaemia (AML), and because it can cross the blood–brain barrier, it is useful in the treatment of central nervous system lymphomas. However, the response is variable, and resistance commonly develops via multiple mechanisms. Its activity is dependent on the intracellular concentrations of the active phosphorylated form, and one of the main mechanisms of resistance involves the deficiency of the transporter molecule hENT1 that carries it into the cells. As a result, Clavis Pharma developed a lipophilic ester derivative, elacytarabine, whose cellular uptake is not hENT1-dependent.1

- See more at:http://www.manufacturingchemist.com/technical/article_page/Anticancer_agent__elacytarabine/83035

 http://www.manufacturingchemist.com/technical/article_page/Anticancer_agent__elacytarabine/83035#sthash.bF8Vqa3M.dpuf

Cancer drug tested in pet dogs is now bound for human trials

PAC 1
Thanks to a new $2 million investment, a drug that spurs cancer cells to self-destruct while sparing healthy cells is on the road to human clinical trials. The compound, known as PAC-1, has so far proven safe and has promising anti-cancer effects in cell culture, in mouse models of cancer and in pet dogs with spontaneously occurring lymphomas and osteosarcomas.

If PAC-1 (pack one) makes it through the U.S. Food and Drug Administration’s Investigational New Drug review, the first human (Phase I) clinical trial of the drug will begin in mid-2014. The investor, who wishes to remain anonymous, has an option to invest another $2 million to take the drug into human trials. The clinical work will be conducted at the University of Illinois Cancer Center in Chicago.

http://news.illinois.edu/news/13/0717cancer_drug_PaulHergenrother_TimFan.html

Photo by
L. Brian Stauffer

---

University of Illinois chemistry professor Paul Hergenrother, left, and veterinary clinical medicine professor Tim Fan led a study of an anti-cancer compound in pet dogs that is now headed for human clinical trials.
PAC-1 (first procaspase activating compound) is a synthesized chemical compound that selectively induces apoptosis, or cell suicide, in cancerous cells. PAC-1 has shown good results in mouse models and is being further evaluated for use in humans. In 2010 a published study showed PAC-1 to be safe to research dogs, and a second study published later that same year reported that a PAC-1 derivative (called S-PAC-1) was well tolerated in a small Phase I Clinical Trial of pet dogs with lymphoma. Even at low doses of S-PAC-1, tumors regressed in 1/6 dogs, and the disease was stabilized (no additional tumor growth) in 3/6 dogs

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 ...

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

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

Role of computers in drug design1

allow slideshare to load...........

Role of computers in drug design1 from Educationcareer,authorstream




 

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.

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

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Jun 7, 2013 – To track information on drugs on worldwide basis, all aspects covered, A group by DR ANTHONY MELVIN CRASTO Ph.D.

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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