Indian biopharma giant Biocon clocks revenue worth $121 mn

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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).

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

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

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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

http://cen.acs.org/articles/91/i30/B-Family-Album.html

Tesaro begins phase III trial of niraparib for treatment of ovarian cancer

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Jul 292013

niraparib

MK-4827

MK-4827 Formula: C19H20N4O

MK-4827 Storage: at -20 ℃ 2 years
MK-4827 CAS No.: 1038915-60-4

MK-4827 is an inhibitor of PARP 1 and 2 with IC50 = 3.8 and 2.1 nM, respectively, currently in clinical trials. In a whole cell assay, it inhibited PARP activity with EC50 = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10-100 nM range. MK-4827 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer

TESARO, Inc. an oncology-focused biopharmaceutical company, today announced that it has initiated patient enrollment in a Phase 3 trial of niraparib, an inhibitor of poly ADP-ribose polymerase (PARP), for the treatment of ovarian cancer. This trial, referred to as NOVA, will evaluate a single daily 300 milligram dose of niraparib in 360 patients with high grade serous, platinum sensitive, relapsed ovarian cancer compared to placebo.
Read more:

http://www.benzinga.com/news/13/07/3773861/tesaro-initiates-phase-3-trial-of-niraparib-for-treatment-of-patients-with-ovaria?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+benzinga+%28Benzinga+News+Feed%29

Biological Activity of MK-4827:
MK-4827 is a potent, selective, PARP 1/2 inhibitor with IC50 of 3.8 and 2.1 nM for PARP1 and 2, respectively. MK-4827 possesses potential antineoplastic activity. In a whole cell assay, MK-4827 prevented PARP activity with an EC50 of 4 nM, enhancing the accumulation of DNA strand breaks and promoting genomic instability and apoptosis. MK-4827 induces selective synthetic lethality in homologous recombination (HR) repair deficient tumors with BRCA1 / 2 loss and tumor cell lines with non-BRCA-related HR defects, supporting clinical utility in sporadic tumors. MK-4827 reveals good pharmacokinetic properties and is currently in phase I clin. trials. The phase I clinical trials for MK-4827 is ongoing in the treatment of solid tumors.

References on MK-4827:
1. Study of the Safety and Efficacy of MK-4827 Given With Temozolomide in Participants With Advanced Cancer (MK-4827-014 AM1).2. A Study of MK4827 in Participants With Advanced Solid Tumors or Hematologic Malignancies (MK-4827-001 AM8).

3. PARP inhibitor MK4827
Abstract
An inhibitor of Poly (ADP-ribose) polymerase (PARP) with potential Antineoplastic Activity. PARP Inhibitor MK4827 inhibits PARP Activity, ENHANCING the accumulation of DNA Strand Breaks and promoting genomic instability and apoptosis. The PARP family of Proteins detect and repair single strand DNA breaks by the base-excision repair (BER) pathway.

4. Glendenning J, Tutt A. PARP inhibitors – Current Status and the Walk towards Early Breast cancer. Breast. 2011 Oct; 20 Suppl 3: S12-9.
Abstract
… Early Phase Trials with efficacy endpoints have been presented for the PARP inhibitors AG014699, olaparib, veliparib, iniparib and MK4827. The results of the first phase II trials exploring monotherapy PARP inhibitor strategies, which are based on revisiting the concept of synthetic lethality, have emerged and are reviewed herein. The clinical trials that have or are exploring combinations with DNA damaging therapy in these contexts are discussed with particular reference to breast cancer, as are biomarkers that have been proposed and are being investigated to develop optimal drug schedule and patient selection criteria for these DNA repair targeting approaches.

5. Jones, Philip; Altamura, Sergio; Boueres, Julia et al. Discovery of 2 – {4 – [(3S)-Piperidin-3-yl] phenyl}-2H-INDAZOLE-7-carboxamide (MK-4827): A Novel Oral Poly (ADP-ribose) polymerase (PARP) Inhibitor efficacious in BRCA-1 and -2 Mutant Tumors. Journal of Medicinal Chemistry (2009), 52 (22), 7170-7185.
Abstract
… We Disclose the Development of a novel series of 2-phenyl-2H-indazole-7-carboxamides as poly (ADP-ribose) polymerase (PARP) 1 and 2 inhibitors. This series was optimized to improve enzyme and cellular activity, and the resulting PARP inhibitors display antiproliferation activities against BRCA-1 and BRCA-2 deficient cancer cells, with high selectivity over BRCA proficient cells. Extrahepatic oxidation by CYP450 1A1 and 1A2 was identified as a metabolic concern, and strategies to improve pharmacokinetic properties are reported. These efforts culminated in the identification of 2 – {4 – [(3S)-piperidin-3-yl] phenyl}-2H-indazole-7-carboxamide 56 (MK-4827), which displays good pharmacokinetic properties and is currently in phase I clinical trials. This compound displays excellent PARP 1 and 2 inhibition with IC50 = 3.8 and 2.1 nM, respectively, and in a whole cell assay, it inhibited PARP activity with EC50 = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10? 100 nM range. Compound 56 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.

DRUG MANUFACTURING

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Jul 282013

Anthony crasto manufacturing presentation from ANTHONY MELVIN CRASTO Ph.D

Lower your cholesterol naturally

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Jul 282013

thereare several ways
1 exercise
2 ayurveda
3 diet
etc

video 1

video 2

video 3

AstraZeneca: FDA-RESUBMISSION OF THE NDA FOR DAPAGLIFLOZIN FOR THE TREATMENT OF TYPE 2 DIABETES

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Jul 272013

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

Health Canada approves two GSK drugs for metastatic melanoma

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Jul 262013

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

Probiotic Could Prevent Kidney Stones

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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

Galapagos Delivers Novel Osteoarthritis Molecules in Alliance with Servier

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Jul 242013

Galapagos NV announced today the achievement of a late stage discovery milestone for small molecules against a novel target in the osteoarthritis (OA) alliance with Servier.

http://www.pharmpro.com/news/2013/07/galapagos-delivers-novel-osteoarthritis-molecules-alliance-servier?et_cid=3383427&et_rid=519587661&type=cta

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

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Jul 232013

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]

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 (help) edit
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 (help) edit
ClinicalTrials.gov NCT00890825 Comparison of AZD6244 in Combination With Docetaxel Versus Docetaxel Alone in KRAS Mutation Positive Non Small Cell Lung Cancer (NSCLC) Patients
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