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Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

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DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc 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 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

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Genzyme’s multiple sclerosis treatment approved by European Commission

Sanofi and its subsidiary Genzyme have been given marketing approval by the European Commission for Lemtrada (alemtuzumab), a treatment for multiple sclerosis.  read all at

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Genzyme’s multiple sclerosis treatment approved by European Commission

Bayer’s Stivarga® (regorafenib) Tablets Approved in Europe

WHIPPANY, N.J. and SOUTH SAN FRANCISCO, Calif., Aug. 30, 2013 /PRNewswire/ — Bayer HealthCare and Onyx Pharmaceuticals, Inc. (NASDAQ: ONXX) announced today that the European Commission has approved Stivarga® (regorafenib) tablets for the treatment of adult patients with metastatic colorectal cancer (mCRC).

In September 2012, Stivarga was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy.





cas 755037-03-7

4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide hydrate

February 25, 2013 — The U.S. Food and Drug Administration today expanded the approved use of Stivarga (regorafenib) to treat patients with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease.

GIST is a tumor in which cancerous cells form in the tissues of the gastrointestinal tract, part of the body’s digestive system. According to the National Cancer Institute, an estimated 3,300 to 6,000 new cases of GIST occur yearly in the United States, most often in older adults.

Stivarga, a multi-kinase inhibitor, blocks several enzymes that promote cancer growth. With this new approval, Stivarga is intended to be used in patients whose GIST cancer cannot be removed by surgery or has spread to other parts of the body (metastatic) and is no longer responding to Gleevec (imatinib) and Sutent (sunitinib), two other FDA-approved drugs to treat GIST.

“Stivarga is the third drug approved by the FDA to treat gastrointestinal stromal tumors,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “It provides an important new treatment option for patients with GIST in which other approved drugs are no longer effective.”

Stivarga was approved in September 2012 to treat colorectal cancer. It is marketed by Bayer HealthCare Pharmaceuticals, based in Wayne, N.J. Gleevec is marketed by East Hanover, N.J.-based Novartis, and Sutent is marketed by New York City-based Pfizer.

Regorafenib (BAY 73-4506, commercial name Stivarga) is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase (RTK). Regorafenib shows anti-angiogenic activity due to its dual targetedVEGFR2-TIE2 tyrosine kinase inhibition. It is currently being studied as a potential treatment option in multiple tumor types.[1]

Metastatic colorectal cancer

Regorafenib demonstrated to increase the overall survival of patients with metastaticcolorectal cancer[2] and has been approved by the US FDA on September 27, 2012.[3]Stivarga is being approved with a Boxed Warning alerting patients and health care professionals that severe and fatal liver toxicity occurred in patients treated with Stivarga during clinical studies. The most common side effects reported in patients treated with Stivarga include weakness or fatigue, loss of appetite, hand-foot syndrome (also called palmar-plantar erythrodysesthesia), diarrhea, mouth sores (mucositis), weight loss, infection, high blood pressure, and changes in voice volume or quality (dysphonia).[4]

  1.  “Bayer Announces New Data on Oncology Portfolio To Be Presented at the ECCO-ESMO Congress 2009″. Retrieved 2009-09-19.
  2. “Phase III Trial of Regorafenib in Metastatic Colorectal Cancer Meets Primary Endpoint of Improving Overall Survival”. Retrieved 2011-10-26.
  3. “FDA approves new treatment for advanced colorectal cancer”. 27 Sep 2012.
  4. “FDA Prescribing Information”. 27 Sept 2012.

Regorafenib from the structure consists of three simple aromatic ring structure, which fragments can be connected from urea by the corresponding two aniline with phosgene or triphosgene prepared by oxygen fragments can be connected SNAr from the corresponding phenol by reaction of. Carboxylic acid 1 by esterification of Thionyl Chloride 2 , methyl amine solution to 2 the ester group is converted to an amide to obtain 3 , 3 , and 4 in alkaline conditions by SNAr reaction of 5 , 5 , and then the isocyanate 6 ( from the corresponding aniline with phosgene or triphosgene was obtained) to obtain the Regorafenib.

GLENMARK-A new way for a new world


Type Public
Traded as BSE532296NSEGLENMARK)
Industry PharmaceuticalsDrugs &Healthcare
Founded 1977
Founder(s) Gracias Saldanha
Headquarters MumbaiMaharashtra[1]India
Key people Glenn Saldanha, MD & CEO [2]
Products Medicines and Vaccines
Revenue INR1031.10 crore(US$160 million) (2009–2010)[3]
Employees 7,000 [4]
Subsidiaries Glenmark Generics Ltd[5]

Glenmark Pharmaceuticals is a pharmaceutical company headquartered in MumbaiIndia[6] It manufactures and markets generic formulation products and active pharmaceutical ingredients (API), both in the domestic and international markets. In the formulation business, its business spans segments such as DermatologyInternal MedicinePaediatricsGynaecologyENT andDiabetes.

It has four manufacturing facilities for formulations and additional three facilities for APIs. These manufacturing facilities are located in the states of MaharashtraGoaHimachal Pradesh and Gujarat in India.

It operates in 95 countries through its subsidiaries, Glenmark Pharmaceuticals USA, Glenmark Pharmaceuticals UK. Glenmark Pharmaceuticals SA. [7]


  2.  “If I were FM | Glenn Saldanha, managing director and CEO, Glenmark Pharmaceuticals – Economy and Politics”. 2009-07-01. Retrieved 2010-09-30.
  3.  “BSE Plus”. Retrieved 2010-09-30.
  4. Glenmark Pharmaceuticals Ltd. (2529483): Stock Quote & Company Profile – BusinessWeek”. Retrieved 2010-09-30.
  5.  “Glenmark Pharmaceuticals | TopNews”. Retrieved 2010-09-30.
  6.  “about Glenmark Pharmaceuticals”. Retrieved 2010-09-30.
  7.  “Glenmark Pharmaceuticals acquires Bouwer Bartlett, South Africa”. 2005-12-26. Retrieved 2010-09-30.

WORLD-CLASS CAPABILITIEIS: Glenn Saldanha (left), Managing Director and CEO, along with Dr. Michael Buschle, President Biologics, Glenmark Pharmaceuticals at a press conference in Mumbai on Monday. Photo: Paul Noronha


Glenmark Pharma – The persevering innovator

Glenn Saldanha, chairman, Glenmark Pharmaceuticals Ltd

Every Tuesday, unmindful of the gridlocked traffic, Glenn Saldanha, the 43-year-old Chairman of Glenmark Pharmaceuticals Ltd, or GPL, makes it a point to visit his research centre at Mahape in Navi Mumbai. It is the hub of Glenmark’s focus on creating new chemical entities, or NCEs, R&Dspeak for original drugs. Leading the innovation for Saldanha are his lab coat-clad scientists and researchers peering into the test tubes, burettes and pipettes at the Mahape facility.

“Almost 30 to 40 per cent of my time spent on business goes into issues relating to innovation,” he says. That includes thinking about research strategy, deciding on which chemical targets to focus on and which therapeutic segments to chase, and even hiring key R&D talent. Today, out of Glenmark’s 600-odd scientists, 400 are involved in NCE research.

The past 13 years have convinced the ardent admirer of Steve Jobs, the iconic former CEO of Apple, that the future lies in innovation. “If you look at how some of the largest corporations of the world were built, it is clear you need to have innovative products,” says Saldanha, a pharmacist by training, who voraciously reads scientific journals to stay updated on current scientific thought and trends. “Look at what Apple has created… that is the way to build a mega corporation, and that is the key reason why, despite our setbacks, we believe so heavily in innovation.”

Creating an NCE has been the Holy Grail for Indian pharma companies, including giants such as Dr Reddy’s Laboratories and Ranbaxy Laboratories (now owned by Daiichi Sankyo of Japan), but without any major success so far. These companies have reviewed their focus on NCE research and some branched into related activities like differentiated products. So has Glenmark, but it also soldiers on with drug discovery as its key focus area. With five molecules currently undergoing trials in various phases, the company now leads the charge of the Indian drug research industry.

Even one successful launch, say that of revamilast (for asthma and rheumatoid arthritis), which has potential peak sales of $2 billion worldwide, could change the fortunes of the company, though one can never be sure till it actually happens. Next year, Glenmark is likely to have half a dozen compounds in Phase II human trials. Saldanha hopes to hit the market with one or more of his drugs between 2015 and 2017. This potential upside is precisely why Glenmark is in this listing of Tomorrow’s Goliaths, and not any of the other bigger or faster-growing companies.

Undiminished zest
“Every year we expect two more molecules to get into clinical trials,” says Saldanha, his zest undiminished by past failures. “In 2008, in a span of one or two quarters, our entire pipeline pretty much got wiped out, but we never lost our commitment and passion.” At that time its most advanced molecule, oglemilast, used for treating patients with chronic obstructive pulmonary disease, had to be abandoned when its Phase IIb trials produced unsatisfactory results. It also had to suspend clinical development of GRC 6211, a compound for treating osteoarthritis pain, because of side effects.

Unlike other companies that reduced NCE development efforts when faced with similar situations, Glenmark persevered. “We never downsized our research team and did not cut back on budgets,” says Saldanha. “We did not even cut travel and our scientists continued to participate in major global conferences.” It is hardly surprising that his core R&D team has stayed put. Consider Neelima Joshi, 48, Senior Vice President and Head of NCE R&D, who was part of the dozen-odd people who set up the Mahape facility in 2000.

Even then, she says, Glenmark’s management was clearly focused on innovation and the move was in anticipation of the product patent regime that was to come in 2005. It was the impending change in India’s patent law that shaped the mind of the 29-year-old Saldanha in 1998, when he returned to India after working with Eli Lilly and PricewaterhouseCoopers to run his father Gracias Saldanha’s formulations business. After India became a signatory to General Agreement on Tariffs and Trade, it changed its patent law in 2005 from a process patent, which encouraged creation of copies of blockbuster original drugs with minor process changes, to a product patent, where the original drug’s patent itself is recognised in India, thereby prohibiting the creation of copies. This key change, and Saldanha’s passion for research, convinced him to steer Glenmark the NCE way.

However, not everyone agrees with Glenmark’s approach to NCE development, especially of giving away a promising molecule in the early stages to big multinational companies for further R&D. The argument: outlicensing a molecule at a later stage can give a company better valuations. The alternative is to do what Piramal Healthcare wants to – not outlicense. “We believe in taking the drug from the bench to market,” says Dr Swati A. Piramal, Vice Chairperson of Piramal Healthcare, which hopes to deploy the funds it got from sale of its formulations business to Abbott for its R&D efforts. “We are now at the end of the 10 years, having begun in 2002, and we hope between 2012 and 2015, we will hit the market with a new drug.”

While Piramal’s approach is a bench-to-market one, others such as Sun Pharma have developed a different model. Sun Pharma has created a separate research entity called Sun Pharma Advanced Research Centre, better known as SPARC, whose sustainability is built by making differentiated and innovative “generic-plus” products (in simple language, the risk is less, as the basic ingredient is known, but the company is developing a patented technology and a better-targeted product with intellectual property built in). What is more, the returns from this are to help fund the research programme.

On the other hand, Hyderabadbased Dr Reddy’s, one of the pioneers of India’s drug discovery journey, has today rationalised its research programme. It had, in fact, tried out a unique model of creating the country’s first integrated drug development company, Perlecan Pharma, which had equity capital commitments from ICICI Venture and other investors. But it soon saw the outside investors exit and brought back Perlecan into the Dr Reddy’s fold after delays in progress of candidates were not acceptable to some partners who had wanted early monetisation.

Beyond NCEs
Dr Reddy’s has now widened its scope beyond NCEs to differentiated products and formulations where improvements are made on existing products that have limited competition in the market. Its only Phase III candidate, balaglitazone, a diabetes drug, has yet to deliver the goods; the asset class it belongs to, glitazone, has had to deal with an overhang of safety concerns, especially in cases where there is a prolonged use of the drug. Yet, Dr Reddy’s sees sense in Glenmark’s model. “It is a viable model and a right strategy for a small company as Indian companies do not have the capacity to take the drug on their own to the market,” says Satish Reddy, Chief Operating Officer and Managing Director of Dr Reddy’s. “They will need to depend on upfront and milestone payments, and royalties.”

Analysts are cautiously optimistic as Glenmark will have some six compounds in Phase II only next year. Plus the fact that Glenmark has still not hit the market with a new drug weighs it down. “It has had no material success so far; they may make it big but it is difficult to say right now,” says a Mumbai-based analyst.

Neelima Joshi Senior VP and Head, NCE R&D
Even in 2000, our management was clearly focused on innovation and the move was in anticipation of the product patent regime that was to come: Neelima Joshi

On his part, Saldanha argues that he has already recovered his R&D investments. “Till date, we have spent about $120 million in innovation research; against that we have got around $200 million as upfront and milestone payments.”

Says Nomura Financial Advisory and Securities in a recent report: “Glenmark has generated outlicensing income every year from 2004/05 to 2011/12 – except 2008/09. Average licensing income has been Rs 1 billion over the eightyear period. With seven development assets in the pipeline, we believe Glenmark will be able to continue to book licensing income, although the quantum and timing cannot be predicted.”

With standalone revenues of Rs 1,154.63 crore and consolidated revenues of almost Rs 3,000 crore, Glenmark hopes to hit the $1-billion mark soon. And if one of the NCEs sails through, the impact on the topline will be significant – a huge distance travelled for a company that clocked less than Rs 100 crore in the late 1990s. Certainly, Saldanha’s long drives on the Mumbai roads to his R&D headquarters are proving worthwhile.



Soliris Gets Thumbs Up From EMA’s COMP


CAS number   219685-50-4

Alexion’s Soliris® (eculizumab) Receives Positive Opinion from the Committee for Orphan Medicinal Products for Treatment of Neuromyelitis Optica (NMO)

Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced that Soliris® (eculizumab), the company’s first-in-class terminal complement inhibitor, has received a positive opinion for orphan medicinal product designation from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) for the treatment of neuromyelitis optica (NMO), a life-threatening, ultra-rare neurological disorder. The positive opinion of the COMP has now been forwarded to the European Commission for final approval and publication in the community register. Soliris is not approved in any country for the treatment of patients with NMO


Soliris is a formulation of eculizumab which is a recombinant humanized monoclonal IgG2/4;κ antibody produced by murine myeloma cell culture and purified by standard bioprocess technology. Eculizumab contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-chain variable regions. Eculizumab is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a molecular weight of approximately 148 kDa.


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).[1] It costs £400,000 ($US 600,000) per year per patient.[1]

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.[2][3]

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.[1][4][5][6] Clinical trials in patients with aHUS demonstrated inhibition of thrombotic microangiopathy (TMA),[7] the formation of blood clots in small blood vessels throughout the body,[1][3][4] including normalization of platelets and lactate dehydrogenase (LDH), as well as maintenance or improvement in renal function.[7]

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

  1. Hillmen, Young, Schubert, P, N, J, et al (2006). “The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria”.N Engl J Med 355 (12): 1233–1243. doi:10.1056/NEJMMoa061648PMID 16990386.
  2. Noris, Caprioli, Bresin, M, J, E, et al. (2010). “Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype”. Clin J Am Soc Nephrol 5: 1844–1859.
  3. Caprioli, Noris, Brioschi, J, M, S, et al (2006). “Genetics of HUS: the impact of MPC, CFH, and IF mutations on clinical presentation, response to treatment, and outcome”. Blood 108: 1267–1279.
  4.  Hillman, Hall, Marsh, P, C, JC, et al (2004). “Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria”. N Eng J Med 350: 552–559.
  5.  Ray, Burrows, Ginsberg, Burrows, JG, RF, JS, EA (2000). “Paroxysmal nocturnal hemoglobinuria and the risk of venous thrombosis: review and recommendations for management of the pregnant and nonpregnant patient”. Haemostasis 30: 103–107.
  6.  Kelly, Hill, Arnold, RJ, A, LM, et al (2011). “Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival”. Blood 117: 6786–6792.
  7. .Soliris® (eculizumab) prescribing information (2011). Cheshire, CT: Alexion Pharmaceuticals.

Roche may bid for Alexion, gets Erivedge EU approval


Erivedge , Vismodegib

The molecule also is known as GDC-0449 and RG3616.

read all at

Vismodegib works by interfering with the membrane protein Smoothened, which provides positive signals to the Hh pathway. At present, there are no FDA-approved drugs targeting Hh signaling, although the pathway is the focus of investigation in a variety of cancers.

Meantime, Roche has obtained conditional European approval for Erivedge (vismodegib) for the treatment of adults with symptomatic metastatic basal cell carcinoma (BCC) or locally advanced BCC inappropriate for surgery or radiotherapy.

The Basel-based group noted that the approval makes Erivedge, a capsule taken once-a-day, the first licensed medicine for patients in the European Union “with this disfiguring and potentially life-threatening form of skin cancer”. Chief medical officer Hal Barron said the green light “is great news for patients with advanced basal cell carcinoma, who previously had no medicines to treat their disease”, adding that Erivedge substantially reduced tumour size in patients in clinical trials.

Under the conditional approval, Roche will provide additional data from an ongoing global safety study. Erivedge was approved by the US Food and Drug Administration in January 2012 following a priority review.

Vismodegib (trade name Erivedge) is a drug for the treatment of basal-cell carcinoma(BCC). The approval of vismodegib on January 30, 2012, represents the first Hedgehog signaling pathway targeting agent to gain U.S. Food and Drug Administration (FDA) approval.[1] The drug is also undergoing clinical trials for metastatic colorectal cancer,small-cell lung cancer, advanced stomach cancerpancreatic cancermedulloblastomaand chondrosarcoma as of June 2011.[2] The drug was developed by the biotechnology /pharmaceutical company Genentech, which is headquartered at South San Francisco, CaliforniaUSA.

Vismodegib is indicated for patients with basal cell carcinoma (BCC), which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation.[3]

Hedgehog Activation.

The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the hedgehog signaling pathway.[2] SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway.[4] This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.[5]

Hedgehog pathway
Ligand-dependent Hedgehog signaling.


  1.  “Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients”.
  1.  “Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients”.
  2.  Molecule of the Month. June 2011.
  3.  “FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma”.
  4.  “Vismodegib (GDC-0449) Smoothened Inhibitor – BioOncology”.
  5.  H. Spreitzer (4 July 2011). “Neue Wirkstoffe – Vismodegib”. Österreichische Apothekerzeitung (in German) (14/2011): 10.

Vismodegib is Hedgehog (Hg) path inhibitors. Pka = 3.8 (pyridinium cation); soluble 0.1μg/mL (pH = 7), 0.99mg/mL (pH = 1), logP = 2.7. Vismodegib can be synthesized by the following route:




Please wait and allow slideshare to load…………..

EU OKs Blood Cancer Drug Iclusig




ARIAD Announces Marketing Authorization for Iclusig® (ponatinib) in the European Union
CAMBRIDGE, Mass. & LAUSANNE, Switzerland–(BUSINESS WIRE)–Jul. 2, 2013– ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced that the European Commission (EC) has granted a marketing authorization for Iclusig® (ponatinib) as an orphan medicinal product for two indications:read all at


Ponatinib (Iclusig, previously AP24534) is an FDA approved oral drug candidate developed by ARIAD Pharmaceuticals for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). It is a multi-targeted tyrosine-kinase inhibitor. Some forms of CML, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors.

Oncologists have complained, however, that many patients can’t afford the “astronomical” cost of $138,000 a year, which makes it one of the most expensive drugs in medicine, and far more expensive than what is needed to pay the development costs.

Ponatinib was approved by the US FDA on December 14, 2012, for patients with resistant or intolerant CML and Ph+ ALL, based on results of the PACE phase II trial reported days earlier at the annual ASH meeting.Because the approval was under the FDA’s accelerated approval program the applicant will be required to carry out additional studies.

The PACE (Ponatinb Ph+ ALL and CML Evaluation) pivotal phase II trial started enrolling patients in September 2010 and is designed to provide definitive clinical data for regulatory approval in this setting. Good results were reported in Dec 2012.

At the 2010 annual meeting of the American Society of Hematology, ARIAD announced from a Phase I study of ponatinib in patients with resistant and refractory chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). The study demonstrated that in chronic-phase CML patients treated with ponatinib, 66 percent of patients in the trial achieved a major cytogenetic response, including 100 percent of patients who also had a T315I mutation

Vitaros Approved in 10 Countries

Vitaros, alprostadil

7-[(1R,3R)-3-hydroxy-2-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid

Apricus Biosciences Inc. said that its impotence drug Vitaros has been approved in 10 European countries. The company said Vitaros is now approved in the Netherlands, Germany, France, Italy, and the U.K., among other countries, for the treatment of erectile dysfunction.

The active ingredient in Vitaros, alprostadil, is an ingredient in other approved impotence treatments and Apricus is also studying it as a treatment for female sexual arousal disorder.

Prostaglandin E1 (PGE1), known pharmaceutically as alprostadil,[1] is a prostaglandin. It is a drug used in the treatment of erectile dysfunction[2] and has vasodilatory properties.

Patent ductus arteriosus

Alprostadil is also used in maintaining a patent ductus arteriosus in newborns. This is primarily useful when there is threat of premature closure of the ductus arteriosus in an infant with ductal-dependent congenital heart disease, including cyanotic lesions (e.g., pulmonary atresia/stenosis, tricuspid atresia/stenosis, transposition of the great arteries) and acyanotic lesions (e.g., coarctation of the aorta, hypoplastic left heart syndrome, critical aortic stenosis, interrupted aortic arch).

Sexual dysfunction

Alprostadil is sold in the United States as urethral suppositories and in injectable form. The suppositories are sold under the brand name MUSE.[3] The injectable forms are Edex[4] and Caverject.[5] Muse delivers alprostadil as a penile suppository, inserted into the urethra, at least ten minutes before the erection will be needed. Caverject and Edex are similarly fast-acting, but instead are injected by syringe directly into the corpus cavernosum of the penis.

Apricus Biosciences is developing proprietary drugs; Vitaros for men with erectile dysfunction, Femprox for female sexual arousal disorder and RayVa for Raynaud’s phenomenon. Two Phase III studies have been completed for Vitaros, and approval has been granted in Canada. Apricus Biosciences is seeking regulatory approval in Europe, South America, and other territories. Apricus Biosciences sold the rights for Vitaros in the US to Warner Chilcott.[6]

Alprostadil is also available as a generic. The major cost is that it must be mixed by a compounding pharmacy and supplies of alprostadil may be difficult to obtain. There are different formulations, including Bimix and Trimix, which may include papaverine and/or phentolamine. A typical mix might be 30 mg of papaverine, 2 mg of phentolamine, and 20 mcg alprostadil. As a generic, it is much less expensive than the pre-packaged injectables. It is premixed and must be kept refrigerated and the user must load a syringe with the quantity needed.

Critical limb ischemia

Alprostadil is also used for critical limb ischemia. It increases blood flow by peripheral vasodilation within 5 minutes and induces angiogenesis. It is most effective when the ankle pressure is at least 30 mmHg and at least one tibial artery is patent.

  1.  Cawello W, Leonhardt A, Schweer H, Seyberth HW, Bonn R, Lomeli AL (September 1995). “Dose proportional pharmacokinetics of alprostadil (prostaglandin E1) in healthy volunteers following intravenous infusion”. British Journal of Clinical Pharmacology 40 (3): 273–6. PMC 1365109. PMID 8527291.
  2.  Harding LM, Adeniyi A, Everson R, Barker S, Ralph DJ, Baranowski AP (December 2002). “Comparison of a needle-free high-pressure injection system with needle-tipped injection of intracavernosal alprostadil for erectile dysfunction”. International Journal of Impotence Research 14 (6): 498–501. doi:10.1038/sj.ijir.3900916. PMID 12494285.
  3.  “Muse Suppository – Facts and Comparisons”. Retrieved 4 January 2013.
  4.  Edex – Facts and Comparisons
  5.  Caverject – Facts and Comparisons
  6.  Fain Hughes (2007-10-29). “NEXM: Dutton Sees Strong Speculative Buy and 12-Month Price Double”. Retrieved 2007-11-01.

Prostaglandin E1 (alprostadil, PGE1) erectile dysfunction drug, molecular model. PGE1 is a prostaglandin used in the treatment of erectile dysfunction. Stock Photo - 17817688
Prostaglandin E1 (alprostadil, PGE1) erectile dysfunction drug, molecular model. PGE1 is a prostaglandin used in the treatment of erectile dysfunction.

Sanofi Updates Lantus Label in EU, ORIGIN Results on Lantus® Cardiovascular Safety Integrated Into European Union Product Label

Lantus® (insulin glargine)

June 5, 2013 –

Sanofi  announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for inclusion in the Lantus® (insulin glargine) product label of safety and efficacy data from the insulin glargine cardiovascular (CV) outcomes trial ORIGIN (Outcome Reduction with Initial Glargine INtervention). The revised label is evidence of Sanofi’s ongoing commitment to further assert the well-known safety and efficacy profile of insulin glargine, the most-studied basal insulin. The indication for the use of Lantus® remains unchanged.

Mechanism of Action
Insulin glargine (lantus) mechanism of action.

LANTUS (insulin glargine rdna origin injection) consists of insulin glargine dissolved in a clear aqueous fluid. Each milliliter of LANTUS (insulin glargine rdna origin injection) contains 100 IU (3.6378 mg) insulin glargine.

LANTUS® is a sterile solution of insulin glargine for use as an injection. Insulin glargine is a recombinant human insulin analog that is a long-acting (up to 24-hour duration of action), parenteral blood-glucose-lowering agent.,  LANTUS (insulin glargine rdna origin injection) is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acidasparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Chemically, it is 21A– Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin and has the empirical formula C267H404N72O78Sand a molecular weight of 6063.

New Rule on Importing Active Pharmaceutical Ingredients (API) to the EU







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