AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

Indian biopharma giant Biocon clocks revenue worth $121 mn

 companies, Uncategorized  Comments Off on Indian biopharma giant Biocon clocks revenue worth $121 mn
Jul 302013
 

 

Kiran Mazumdar-Shaw, chairman and managing director, Biocon.

Indian biopharma giant Biocon reported healthy growth of 22 percent for Q1 FY14 riding on the back of an increased geographical footprint in the emerging markets

 

Bangalore: Indian biopharma giant Biocon reported healthy growth of 22 percent for Q1 FY14. The firm clocked revenues worth $121 million (Rs723 crore), EBITDA of $29.50 million (Rs175 crore); and profit after tax (PAT) of $15.80 million (Rs94 crore).

Read more at: http://www.biospectrumasia.com/biospectrum/news/192549/how-biocon-clock-revenue-worth-usd121-mn#.UfdqX6I3CSo

biocon-s-india-focused-branded-formulations-vertical-as-well-as-research-services-continue-to-grow-at-a-steady-pace

Biocon’s India-focused branded formulations vertical as well as research services continue to grow at a steady pace

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B Family Album -Structural Biology: First structures of class B G protein-coupled receptors may aid drug hunts

 Uncategorized  Comments Off on B Family Album -Structural Biology: First structures of class B G protein-coupled receptors may aid drug hunts
Jul 292013
 
Two new G-Protein Coupled Receptor structures, the glucagon receptor (computer model with extracellular domain) and corticotropin-releasing factor receptor, showing their location on the GPCR family tree.

A computer model of a full-length glucagon receptor (left) and a crystal structure of a corticotropin-releasing factor receptor (right) add details of class B receptors to the class A structures already on the GPCR family tree.
Credit: Katya Kadyshevskaya
As many as 30% of drugs on the market target G protein-coupled receptors (GPCRs), a family of signaling conduits that snake back and forth across cell membranes. But there are several classes of these proteins, and scientists’ knowledge of the structures is almost entirely restricted to just one, the class A subtype. So drugs could be missing a lot of targets. Aim could improve, however, now that researchers have the first two reports of class B GPCR structures (Nature 2013, DOI: 10.1038/nature12357 and10.1038/nature12393
read all at
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AstraZeneca: FDA-RESUBMISSION OF THE NDA FOR DAPAGLIFLOZIN FOR THE TREATMENT OF TYPE 2 DIABETES

 Uncategorized  Comments Off on AstraZeneca: FDA-RESUBMISSION OF THE NDA FOR DAPAGLIFLOZIN FOR THE TREATMENT OF TYPE 2 DIABETES
Jul 272013
 

File:Dapagliflozin structure.svg

DAPAGLIFLOZIN

AstraZeneca and Bristol-Myers Squibb Company today announced that the U.S. Food and Drug Administration (FDA) has acknowledged receipt of the New Drug Application (NDA) resubmission for investigational drug dapagliflozin for the treatment of adults with type 2 diabetes. The FDA assigned a new Prescription Drug User Fee Act goal date of January 11 2014.

The dapagliflozin Phase II/III clinical development program included more than 12,000 adult patients with diabetes (more than 8,000 patients received dapagliflozin) in 26 clinical trials. In response to the FDA’s January 2012 complete response letter requesting additional data to allow a better assessment of the benefit-risk profile of dapagliflozin, the NDA resubmission includes several new studies and additional long-term data (up to four years’ duration) from previously submitted studies, resulting in an overall increase in patient-years exposure to dapagliflozin of more than 50 percent.

Dapagliflozin, an investigational compound, is a selective and reversible inhibitor of sodium-glucose cotransporter 2 (SGLT2), which works independently of insulin. It is currently approved for the treatment of type 2diabetes in the European Union, Australia, Brazil, Mexico and New Zealand

READ ALL AT

http://www.swedishwire.com/press-releases/17843-astrazeneca-fda-acknowledges-receipt-of-resubmission-of-the-new-drug-application-for-investigational-compound-dapagliflozin-for-the-treatment-of-type-2-diabetes

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Health Canada approves two GSK drugs for metastatic melanoma

 health canada, Uncategorized  Comments Off on Health Canada approves two GSK drugs for metastatic melanoma
Jul 262013
 

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Health Canada has approved two GlaxoSmithKline (GSK) drugs, Tafinlar(TM) (dabrafenib mesilate) and Mekinist(TM) (trametinib), for patients with unresectable or metastatic melanoma. Dabrafenib mesylate, which is a BRAF-inhibitor, is indicated as a monotherapy oral treatment for unresectable melanoma or metastatic melanoma in adult …http://www.gsk.ca/english/html/media-centre/2013-07-24.html

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Iron Oxide Nanoparticles Show the Way

 nanotechnology  Comments Off on Iron Oxide Nanoparticles Show the Way
Jul 262013
 

Iron oxide nanoparticles precisely direct stem cells to damage tissues, thereby increasing their therapeutic potential

Read more

http://www.chemistryviews.org/details/news/5039301/Iron_Oxide_Nanoparticles_Show_the_Way.html

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Probiotic Could Prevent Kidney Stones

 Uncategorized  Comments Off on Probiotic Could Prevent Kidney Stones
Jul 252013
 

The discovery of a gene’s function in E. coli and other bacteria might lead to a probiotic to prevent calcium-oxalate urinary stones, the most common type of kidney stone. Human cells can’t metabolize oxalate and high concentrations can result in painful blockages of the urinary tract.

http://www.dddmag.com/news/2013/07/probiotic-could-prevent-kidney-stones?et_cid=3386057&et_rid=523035093&type=cta

 

http://www.precisionnutrition.com/all-about-kidney-stones

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AstraZeneca began a pivotal trial with selumetinib , thyroid cancer, Phase 3 trial

 Phase 3 drug, Uncategorized  Comments Off on AstraZeneca began a pivotal trial with selumetinib , thyroid cancer, Phase 3 trial
Jul 232013
 

File:Selumetinib skeletal.svg

 

selumetinib

Array Biopharma To Report Top-line Results From ARRY-502 Asthma Trial
Sacramento Bee
AstraZeneca began a pivotal trial with selumetinib (an Array-invented drug) in patients with thyroid cancer in May 2013 and expects to begin a Phase 3 trial in patients with non-small cell lung cancer during the second half of 2013. Three other Array

http://www.sacbee.com/2013/07/22/5586413/array-biopharma-to-report-top.html

 

Selumetinib (AZD6244) is a drug being investigated for the treatment of various types of cancer, for example non-small cell lung cancer (NSCLC).

The gene BRAF is part of the MAPK/ERK pathway, a chain of proteins in cells that communicates input from growth factors. Activating mutations in the BRAF gene, primarily V600E (meaning that the amino acid valine in position 600 is replaced by glutamic acid), are associated with lower survival rates in patients with papillary thyroid cancer. Another type of mutation that leads to undue activation of this pathway occurs in the gene KRAS and is found in NSCLC. A possibility of reducing the activity of the MAPK/ERK pathway is to block the enzyme MAPK kinase (MEK), immediately downstream of BRAF, with the drug selumetinib. More specifically, selumetinib blocks the subtypes MEK1 and MEK2 of this enzyme.[1]

In addition to thyroid cancer, BRAF-activating mutations are prevalent in melanoma (up to 59%), colorectal cancer (5–22%), serous ovarian cancer (up to 30%), and several other tumor types.[2]

KRAS mutations appear in 20 to 30% of NSCLC cases and about 40% of colorectal cancer.[1]

A Phase II clinical trial about selumetinib in NSCLC has been completed in September 2011;[3] one about cancers with BRAF mutations is ongoing as of June 2012[update].[4]

  1. Troiani, T.; Vecchione, L.; Martinelli, E.; Capasso, A.; Costantino, S.; Ciuffreda, L. P.; Morgillo, F.; Vitagliano, D. et al. (2012). “Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase a activation in human lung and colorectal cancer cells”. British Journal of Cancer 106 (10): 1648–1659. doi:10.1038/bjc.2012.129. PMC 3349172. PMID 22569000|displayauthors= suggested (helpedit
  2. Davies, H.; Bignell, G. R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H. et al. (2002). “Mutations of the BRAF gene in human cancer”. Nature 417 (6892): 949–954. doi:10.1038/nature00766. PMID 12068308|displayauthors= suggested (helpedit
  3. ClinicalTrials.gov NCT00890825 Comparison of AZD6244 in Combination With Docetaxel Versus Docetaxel Alone in KRAS Mutation Positive Non Small Cell Lung Cancer (NSCLC) Patients
  4. ClinicalTrials.gov NCT00888134 AZD6244 in Cancers With BRAF Mutations

more info…………………………………….

AZD-6244 (Selumetinib) is an orally-available, aminobenzimidazole-based, allosteric inhibitor of MEK1 kinase with an IC50 of 14 nM. [1] IC50 concentrations of
In cellular growth assays, AZD-6244 was more potent in cell lines containing activating B-Raf and Ras mutations, with IC50 values ranging from 59 to 473 nM. In HT-29 and Malme-3M cell studies, AZD-6244 was found to induce G1-S cell cycle arrest, inducing apoptosis after a 2-day incubation period. [1] In Colo-205 xenografts, AZD6244 induced increased levels of cleaved caspase-3, indicating apoptosis. [2]

In diffuse large B-cell lymphoma (DLBCL) lines, nanomolar concentration of AZD-6244 effectively downregulated MEK/ERK target substrates, including c-Myc, Mcl-1, and Bcl-2. [3]


Technical information:

Chemical Formula:   C17H15BrClFN4O3
CAS #:   606143-52-6
Molecular Weight:   457.68
     
Appearance:   White
Chemical Name:   6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide
Solubility:   Up to 100 mM in DMSO
Synonyms:   AZD-6244, AZD 6244, AZD6244, Selumetinib, Selumetinib sulfate, NSC-748727, ARRY-142886

 


Reference:

1. Yeh et al., Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin. Cancer Res. 2007, 13, 1576-1583 Pubmed ID: 17332304
2. Davies et al., AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol. Cancer Ther. 2007, 6, 2209-2219. Pubmed ID: 17699718
3. Bhalla et al., The novel anti-MEK small molecule AZD6244 induces BIM-dependent and AKT-independent apoptosis in diffuse large B-cell lymphoma. Blood, 2011, 118(4), 1052-1061. Pubmed ID: 21628402

 

 

 

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Diabetes – LX4211

 Uncategorized  Comments Off on Diabetes – LX4211
Jul 222013
 

A compound is being investigated as a Type II diabetes treatment by Lexicon Pharmaceuticals, although it is in an early stage of development

LX4211

 

A compound is being investigated as a Type II diabetes treatment by Lexicon Pharmaceuticals, although it is in an early stage of development.

LX4211 is not selective for just sodium glucose co-transporter-2, or SGLT-2 – it also inhibits SGLT-1.1 Inhibiting this second transporter, responsible for the absorption of glucose in the intestines, it also results in an increase in the release of glucagon-like peptide-1 (GLP-1), but might be combated by administering the dual inhibitor in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor to prevent it being activated.

– See more at:

http://www.manufacturingchemist.com/technical/article_page/Diabetes__LX4211/88179

http://www.manufacturingchemist.com/technical/article_page/Diabetes__LX4211/88179#sthash.BVOa03IT.dpuf

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Jul 222013
 

File:Lubiprostone.svg

 

Dr Reddy’s Laboratories Ltd new patent on

Preparation of lubiprostone

Jackson, Mark; Dahanukar, Vilas Hareshwar; Joseph, Suju Chuttippari; Eda, Vishnu Vardhana Verma Reddy; Ramdas, Sandip Khobare

US 20130184476, 18-JUL-2013

IN2011CH2389 13-JUL-2011 priority

NCT01674530, Phase 3

_____________________________________________________

general info in public domain

Lubiprostone (rINN, marketed under the trade name Amitiza) is a medicationused in the management of chronic idiopathic constipation and irritable bowel syndrome. It was approved by the U.S. Food and Drug Administration (FDA) for this purpose on 31 January 2006.

Lubiprostone is used for the treatment of chronic constipation of unknown cause in adults, as well as irritable bowel syndrome associated with constipation in women.

As of 20 July 2006, Lubiprostone has not been studied in children. There is current research underway to determine the efficacy in postoperative bowel dysfunction, and opioid-induced bowel dysfunction.

Synthesis:Sobrera, L. A.; Castaner, J. (2004). Drugs of the Future 29 (4): 336.

Lubiprostone.png

Lubiprostone received approval from the Food and Drug Administration on 29 April 2008 to treat irritable bowel syndrome withconstipation (IBS-C).

 

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Phase II trials of TB drug through open source drug discovery programme to begin soon

 phase 2, Uncategorized  Comments Off on Phase II trials of TB drug through open source drug discovery programme to begin soon
Jul 222013
 

File:PA 824.svg

PA 824

The search for a new tuberculosis drug after many decades and first time through a unique model of open drug discovery programme may finally bear fruits in near future, with India all set for the launch of the phase II clinical trial of the drug candidate.

The drug, coming through the Open Source Drug Discovery (OSDD) programme by Council of Scientific and Industrial Research (CSIR), will go for the clinical trials on drug-resistant TB patients in India very soon. The process of filing for permission from the Drug Controller General of India (DCGI) is on and public sector LRS Hospital for Respiratory and Infectious Diseases, New Delhi, has been selected for trials. This phase II trials will involve around 250-300 patients, sources said.

The drug candidate, Pa824, was synthesised in India long ago. After a series of ownership changes, the molecule was licensed to CSIR for further development now.

http://www.pharmabiz.com/NewsDetails.aspx?aid=76568&sid=1

Tuberculosis (TB) is one of the leading infectious diseases in the world, with approximately one-third of the world’s population harboring the causative agent, Mycobacterium tuberculosis (Mtb). Though previously a disease associated with aristocratic societies, TB is now predominantly a third-world disease, particularly affecting Asian communities and sub-Saharan Africa. Mtb isolates are increasingly resistant to drug therapies: multidrug-resistant TB (MDR TB) or more severely, extensively drug-resistant TB (XDR TB). As a consequence of these emerging strains, it is becoming increasingly apparent that novel drugs are necessary to combat Mtb infections.

PA 824 is an experimental anti-tuberculosis drug.[1][2] The bicyclic nitroimidazole like molecule PA-824 has got a very complex mechanism of action active against both replicating and hypoxic, non-replicating Mycobacterium tuberculosis.Microarray analysis of the mode of action of PA-824 showed a puzzling mixed effect both on genes responsive to both cell wall inhibition (like isoniazid) and respiratory poisoning (like cyanide). The aerobic killing mechanism of this drug appears to involve inhibition of cell wall mycolic acid biosynthesis through an as yet unknown molecular mechanism.The respiratory poisoning through nitric oxide release seemed to be a crucial element of anaerobic activity by PA-824. The effect of PA-824 on the respiratory complex under hypoxic non-replicating conditions was also manifested in a rapid drop in intracellular ATP levels, again similar to that observed by cyanide treatment.[3]PA-824 recently was shown to be safe, well tolerated, and efficacious at doses of 100–200 mg daily in a dose-ranging study among drug-sensitive, sputum smear–positive, adult pulmonary TB patients [4]

  1.  Ginsberg AM, Laurenzi MW, Rouse DJ, Whitney KD, Spigelman MK (September 2009). “Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects”Antimicrob. Agents Chemother. 53 (9): 3720–5.doi:10.1128/AAC.00106-09PMC 2737845PMID 19528280.
  2.  Stover CK, Warrener P, VanDevanter DR, et al (2000). “A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis”. Nature 405 (6789): 962–6. doi:10.1038/35016103PMID 10879539.
  3. Manjunatha U, Boshoff IM Helena, Barry CE (May-Jun 2009). “The mechanism of action of PA-824”Commun Integr Biol. 2 (3): 215–218. PMC 2717523.
  4. http://www.pipelinereport.org/browse/tb-treatments/pa-824

QSAR modeling of the nitroimidazole PA-824. Shown are two hydrogen bond acceptors (green), one hydrogen bond donor (purple), and one hydrophobe (aqua). Credit: NIAID

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