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DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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Drug firms and cancer………… Lucrative lifesavers
The hopes and perils of betting on cancer treatments
NEW weapons are emerging in the war on cancer. That is good news not just for patients but also for drug companies. The biggest ones, faced with falling sales as their existing medicines go off-patent, are investing in smaller firms with promising cancer treatments under development, hoping to secure the next blockbuster.
NATURE’S VIAGRA-Health benefits of pomegranate by – By Dr. Janardhana V Hebbar, Ayurveda Expert
Countless studies have shown the seemingly countless benefits of fruits for a person’s health.
The U.S. Government recommends that people get some servings of fruits every day. Of all the fruits ready in the shop today,
one fruit is at its height of popularity because of its legendary Greek mythology connection and its exoticism-the pomegranate fruit.
READ COMPLETE ARTICLE AT
http://www.askveda.in/blog/health-benefits-of-pomegranate/
Capecitabine Intermediate-cxpharma
Jiangsu Chengxin Pharmaceutical Co., Ltd with total area 60,000m2 and total invested amount of RMB 300 million, is a high-tech joint-stock enterprise established in 2012, located in Binjiang Pharm-Chem Industry Park, Qidong, the outstanding cultural city well known as the Rivers and Seas Pearl in Jiangsu Province, close to Chongming Island with merely one separated river. It takes around 1 hour by car from the manufacturing site to Shanghai, the Yangtze River Delta economic metropoli……More
http://www.cxpharma.com/en/about.asp?id=8
Dear sir,
We are just a manufacturer and very strong in the following intermediates:
Intermediates for Capecitabine:
2′,3′-Di-O-acetyl-5′-deoxy-5-fluorocytidine (CAS: 161599-46-8)
1,2,3-Triacetyl-5-deoxy-D-ribose (CAS: 62211-93-2)
Methyl-5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranoside (CAS: 23202-81-5)
We have the dedicated workshop for Capecitabine intermediate. Our capacity is more than 20MT per month. Our company is complied with the requirement from EU GMP, US FDA and Chinese GMP. Just for your information.
If you are interested in any of above, please let me know.
Looking forward to your early reply.
Best regards,
Runya Wang(Ms) / Sales Department
Add: No.338 Shanghai Road, Binjiang Pharm-Chem
Industry Park, Qidong, Jiangsu, P.R.China 226221
Tel: 0086-513-86029596
Fax: 0086-513-86105399
Email: runya.wang@cxpharma.com
Web: www.cxpharma.com
http://www.cxpharma.com/en/home.asp in english
Roche reports positive Phase II results for experimental eye drug
Lampalizumab
Roche reports positive Phase II results for experimental eye drug
Lampalizumab, an experimental eye drug from Roche, has helped slow down the progression of an advanced form of age-related macular degeneration (AMD) in a Phase II study, the company announced this week.
READ ALL AT
SEE ALSO
Lampalizumab effective in Phase II clinical trial for macular degeneration
Roche’s new drug for age-related macular degeneration, lampalizumab, showed effective in slowing the progression of AMD in patients with advanced disease, shrinking the area of geographic atrophy by 20%. Read More >>
Lampalizumab (INN) is a humanized monoclonal antibody designed for the treatment of geographic atrophy secondary to age-related macular degeneration. It binds to CFD.[1][2]
This drug was developed by Genentech/Roche.
References
FDA grants priority review to Pharmacyclics drug
ibrutinib
FDA grants priority review to Pharmacyclics drug
Pharmacyclics is getting a priority review of its blood cancer treatment by federal regulators. A priority review shortens a drug evaluation by the U.S. Food and Drug Administration from 10 months to six. The acceptance of the application triggers a $75 million milestone payment to Pharmacyclics from Johnson & Johnson’s Janssen unit.
Ibrutinib (USAN[1]), also known as PCI-32765, is an experimental drug candidate for the treatment of various types of cancer. It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton tyrosine kinase (Btk).[2][3][4] Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson’s Janssen Pharmaceutical division for B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and multiple myeloma.[6][7][8]. Ibrutinib was first designed and synthesized at Celera Genomics by Zhengying Pan, who along with a team of chemists and biologists reported in 2007 a structure-based approach for creating a series of small molecules that inactivate BTK through covalent binding to cysteine-481 near the ATP binding domain of BTK[2]. These small molecules irreversibly inhibited BTK by using a Michael acceptor for binding to the target cysteine. In April 2006, Pharmacyclics acquired Celera’s small molecule BTK inhibitor discovery program, which included a compound, PCI-32765 (known as compound 13 in the Pan et al paper) that was subsequently chosen for further preclinical development based on the discovery of anti-lymphoma properties in vivo [5]. Since 2006, Pharmacyclics’ scientists have advanced the molecule into clinical trials and identified specific clinical indications for the drug. [2][3][4] [5] [6][7][8] It also has potential effects against autoimmune arthritis.[9]
Clinical trials
It has given good results in two phase II clinical trials.[10]
Mechanism
In preclinical studies on chronic lymphocytic leukemia (CLL) cells, ibrutinib has been reported to promote apoptosis, inhibit proliferation, and also prevent CLL cells from responding to survival stimuli provided by the microenvironment.[11] In this study, treatment of activated CLL cells with ibrutinib resulted in inhibition of Btk tyrosine phosphorylation and also effectively abrogated downstream survival pathways activated by this kinase including ERK1/2, PI3K, and NF-κB. Additionally, ibrutinib inhibited proliferation of CLL cells in vitro, effectively blocking survival signals provided externally to CLL cells from the microenvironment including soluble factors (CD40L, BAFF, IL-6, IL-4, and TNF-α), fibronectin engagement and stromal cell contact.
In early clinical studies, the activity of ibrutinib has been described to include a rapid reduction in lymphadenopathy accompanied by a transient lymphocytosis, suggesting that the drug might have direct effects on cell homing or migration to factors in tissue microenvironments.[12]
Ibrutinib has been reported to reduce CLL cell chemotaxis towards the chemokines CXCL12 and CXCL13, and inhibit cellular adhesion following stimulation at the B cell receptor.[13][14] Together, these data are consistent with a mechanistic model whereby ibrutinib blocks BCR signaling, which drives cells into apoptosis and/or disrupts cell migration and adherence to protective tumor microenvironments.
References
- ^ Statement on a Nonproprietary Name Adopted by the USAN Council
- ^ Pan, Z; Scheerens, H; Li, SJ; Schultz, BE; Sprengeler, PA; Burrill, LC; Mendonca, RV; Sweeney, MD et al. (2007). “Discovery of selective irreversible inhibitors for Bruton’s tyrosine kinase”. ChemMedChem 2 (1): 58–61. doi:10.1002/cmdc.200600221. PMID 17154430.
|displayauthors=suggested (help) - ^ Celera Genomics Announces Sale of Therapeutic Programs to Pharmacyclics
- ^ United States patent 7514444
- ^ Honigberg, LA; Smith, AM; Sirisawad, M; Verner, E; Loury, D; Chang, B; Li, S; Pan, Z; Thamm, DH; Miller, RA; Buggy (2010). “The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy”. Proceedings of the National Academy of Sciences of the United States of America 107 (29): 13075–80. doi:10.1073/pnas.1004594107. PMID 20615965. Unknown parameter
|firs11=ignored (help) - ^ Janssen Biotech, Inc. Announces Collaborative Development and Worldwide License Agreement for Investigational Anti-Cancer Drug, PCI-32765
- ^ Clinical trials involve PCI-32765
- ^ Clinical trials involve ibrutinib
- ^ Chang, BY; Huang, MM; Francesco, M; Chen, J; Sokolove, J; Magadala, P; Robinson, WH; Buggy, JJ (2011). “The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells”. Arthritis Research & Therapy 13 (4): R115. doi:10.1186/ar3400. PMID 21752263.
- ^ Good News Continues for Ibrutinib in CLL. 8 Dec 2012
- ^ Herman SE, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, Flynn J, Jones J, Blum KA, Buggy J.J., Hamdy A, Johnson AJ, Byrd JC. (2011) Bruton’s tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood 117: 6287-6296
- ^ The Bruton’s tyrosine kinase (BTK) inhibitor PCI-32765 (P) in treatment-naive (TN) chronic lymphocytic leukemia (CLL) patients (pts): Interim results of a phase Ib/II study.J Clin Oncol 30, 2012 (suppl; abstr 6507)
- ^ Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, Keating MJ, O’Brien S, Chiorazzi N, Burger JA. (2012) The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood 119: 1182-1189.
- ^ de Rooij MF, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, Pals ST, Spaargaren M. (2012) The clinically active BTK inhibitor PCI-32765 targets B-cell receptor (BCR)- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood 119: 2590-2594.
External links
- BTK inhibitor PCI-32765, National Cancer Institute Drug Dictionary
The U.S. Food and Drug Administration (FDA) has approved Mirvaso (brimonidine) topical gel for the topical treatment of the facial erythema (redness) of rosacea in adults 18 years of age or older
brimonidine
Mirvaso
Generic Name: brimonidine
Date of Approval: August 23, 2013
Company: Galderma Laboratories, L.P.
Treatment for: Facial Erythema (Redness) of Rosacea
READ ALL AT
http://www.drugs.com/mirvaso.html
Brimonidine (bri-MOE-ni-deen, brand names Alphagan and Alphagan-P) is a drug used to treat open-angle glaucoma or ocular hypertension.
It acts via decreasing synthesis of aqueous humor, and increasing the amount that drains from the eye through uveoscleral outflow. As a treatment for glaucoma, it is usually given in eyedrop form.
Mechanism of action
Brimonidine is an α2 adrenergic agonist.
Alpha 2 agonists, through the activation of a G protein-coupled receptor, inhibit the activity of adenylate cyclase. This reduces cAMP and hence aqueous humour production by the ciliary body.
Peripheral alpha 2 agonist activity results in vasoconstriction of blood vessels (as opposed to central alpha 2 agonist activity that decreases sympathetic tone, as can be seen by the medication clonidine). This vasoconstriction may explain the acute reduction in aqueous humor flow. The increased uveoscleral outflow from prolonged use may be explained by increased prostaglandin release due to alpha adrenergic stimulation. This may lead to relaxed ciliary muscle and increased uveoscleral outflow.[1]
Clinical uses
Brimonidine is indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. It is also the active ingredient of Combigan along with timolol maleate.
In 2013, the FDA approved topical application of brimonidine 0.33% (Mirvaso) for facial erythema or rosacea.
References
- Mosby’s Drug Guide for Nurses (7th edition; Skidmore) 2007.
External links
Portuguese medicine expenditure in hospitals keeps increasing
August 29, 2013 | By Márcio Barra
The Portuguese Government spends almost as much money on the NHS hospitals’ expenses with medicines as with the reimbursement of all drugs sold in pharmacies, according to data revealed by the Portuguese Ministry of Health.
The numbers disclosed show that, in 2012, the state spent about $ 2,200 million with drugs, 1.200 million of which with the reimbursement of medicines sold in pharmacies and 1.000 million with medicines provided in hospitals.
While the expenses on drugs sold in pharmacies are in control, thanks to successive price cuts by the Government over the years – just in 2013, about 1.400 brand drugs had mandatory a 7% price discount – the expenses with medicines in hospitals and debts to the Pharmaceutical Industry grew again this year, both in value and in average payments. This upward trend is ongoing for six consecutive months.
In July, the value…
View original post 124 more words
Citrus And Statins
bergamottin
Citrus And Statins. —Citrus And Statins “” “How Foods and Drugs Collide” provided my first knowledge that 5-geranoxy psoralen (bergamottin) had been identified as the active agent in grapefruit juice implicated in interfering with the so-called statin drugs
( C&ENCitrus And Statins, Sept. 27, page 55 William L. Stanley Carmel, Calif. /articles/88/i49/Citrus-Statins.html 20101206 88 49 /magazine/88/8849.html /departments/letters.html Citrus And Statins Letters Citrus And Statins Chemical & Engineering News Citrus And Statins ACS 2009 IRS Form 990 Available The American Chemical Society’s 2009 Form 990 is now available on ACS’s website.
Chemical & Engineering News, 88(49), December 06, 2010 [Letters] you will have to pay a fee or subscribe
free info from net
Bergamottin is a natural furanocoumarin found principally in grapefruit juice. It is also found in the oil of bergamot orange, from which it was first isolated and from which its name is derived. To a lesser extent, bergamottin is also present in the essential oils of other citrus fruits. Along with the chemically related compound 6′,7′-dihydroxybergamottin, it is believed to be responsible for thegrapefruit juice effect in which the consumption of the juice affects the metabolism of a variety of pharmaceutical drugs.[1]
Chemistry
Chemically, bergamottin and dihydroxybergamottin are linear furanocoumarins functionalized with side chains derived fromgeraniol. They are inhibitors of some isoforms of the cytochrome P450 enzyme, particularly CYP3A4.[2] This prevents oxidative metabolism of certain drugs by the enzyme, resulting in an elevated concentration of drug in the bloodstream.
Normally, the grapefruit juice effect is considered to be a negative interaction, and patients are often warned not to consume grapefruit or its juice when taking medication. However, some current research is focused on the potential benefits of cytochrome P450 inhibition.[3] Bergamottin, dihydroxybergamottin, or synthetic analogs may be developed as drugs that are targeted to increase the oral bioavailability of other drugs. Drugs that may have limited use because they are metabolized by CYP3A4 may become viable medications when taken with a CYP3A4 inhibitor because the dose required to achieve a necessary concentration in the blood would be lowered.[4]
Biosynthesis of bergamottin
Bergamottin is derived from components originating in the shikimate pathway.[5] The biosynthesis of this compound starts with the formation of the demethylsuberosin (3) product which is formed via the alkylation of the umbelliferone (2) compound.[6] The alkylation of the umbelliferone is initiated with the use of dimethylallyl pyrophosphate, more commonly known as DMAPP. The cyclization of an alkyl group occurs to form marmesin (4), which is done in the presence of NADPH and oxygen along with a cytochrome P450 monooxygenase catalyst.[7] This process is then repeated twice more, first to remove the hydroxyisopropyl substituent from marmesin (4) to form psoralen (5), and then to add a hydroxyl group to form bergaptol (6).[8] Bergaptol (6) is next methylated with SAM, S-Adenosyl methionine, to form bergapten (7). The final step in this biosynthesis is the attachment of a GPP, or geranyl pyrophosphate, to the newly methylated bergapten (7) to form the target molecule bergamottin (8).
References
- ^ David G. Bailey, J. Malcolm, O. Arnold, J. David Spence (1998). “Grapefruit juice-drug interactions”. Br J Clin Pharmacol 46 (2): 101–110. doi:10.1046/j.1365-2125.1998.00764.x.PMC 1873672. PMID 9723817.
- ^ Basavaraj Girennavar, Shibu M. Poulose, Guddadarangavvanahally K. Jayaprakasha, Narayan G. Bhat and Bhimanagouda S. Patila (2006). “Furocoumarins from grapefruit juice and their effect on human CYP 3A4 and CYP 1B1 isoenzymes”. Bioorganic & Medicinal Chemistry 14 (8): 2606–2612. doi:10.1016/j.bmc.2005.11.039. PMID 16338240.
- ^ E. C. Row, S. A. Brown, A. V. Stachulski and M. S. Lennard (2006). “Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of CYP3A4”. Org. Biomol. Chem. 4(8): 1604–1610. doi:10.1039/b601096b. PMID 16604230.
- ^ Christensen, Hege; Asberg, Anders; Holmboe, Aase-Britt; Berg, Knut Joachim (2002). “Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers”. European Journal of Clinical Pharmacology 58 (8): 515–520. doi:10.1007/s00228-002-0516-8. PMID 12451428.
- ^ Dewick, P. Medicinal Natural Products:A Biosynthetic Approach, 2nd ed., Wiley&Sons: West Sussex, England, 2001, p 145.
- ^ Bisagni, E. Synthesis of psoralens and analogues. J. Photochem. Photobiol. B. 1992, 14, 23-46.
- ^ Voznesensky, A. I.; Schenkman, J. B. The cytochrome P450 2B4-NADPH cytochrome P450 reductase electron transfer complex is not formed by charge-pairing. J. Biol. Chem. 1992, 267, 14669-14676.
- ^ Kent, U. M.; Lin, H. L.; Noon, K. R.; Harris, D. L.; Hollenberg, P. F. Metabolism of bergamottin by cytochromes P450 2B6 and 3A5. J. Pharmacol. Exp. Ther. 2006, 318, 992-1005
Ward off cancer with super-nutrient lycopene: Here’s the research
(NaturalNews) Men who like pizza, pasta with red sauce, and lasagna have a new excuse to eat more of those dishes upon discovering that lycopene in tomato sauce promotes prostate health. This news has been around for some time.
Learn more: http://www.naturalnews.com/041805_cancer_prevention_lycopene_super_nutrient.html#ixzz2dL4boXcH
Transform your life in 10 minutes with ancient ‘youthing’ practice
NaturalNews) If you need more zest and zip in your life, the secret to these states and more can be found in a set of simple (yet profound) yogic exercises known as the “Five Tibetans.” Developed by Buddhist monks and brought to the West in the 1930s, Tibetan yoga is a series of five movements that improve digestion and circulation while dispelling fatigue and depression. Advocates of the practice rave about the boundless energy, clarity and vitality the short daily sessions produce. And many also believe Tibetan yoga reverses the hands of time, promoting an ageless and disease free body.
Learn more: http://www.naturalnews.com/041813_transform_life_ancient_practice_youthing.html#ixzz2dL3zsuIL
New Drug Approvals 