AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

DR ANTHONY MELVIN CRASTO Ph.D

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 AFRICURE PHARMA as ADVISOR earlier GLENMARK LS Research centre as consultant,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 32 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, [email protected]

Mallinckrodt PLC : Mallinckrodt Pharmaceuticals Announces Positive Phase 3 Efficacy Results for MNK-795, an Extended-Release Oxycodone/Acetaminophen Combination

 Phase 3 drug  Comments Off on Mallinckrodt PLC : Mallinckrodt Pharmaceuticals Announces Positive Phase 3 Efficacy Results for MNK-795, an Extended-Release Oxycodone/Acetaminophen Combination
Sep 062013
 

MALLINCKRODT PLC : Mallinckrodt Pharmaceuticals Announces Positive
4-traders (press release)
Mallinckrodt (NYSE: MNK) today reported data that investigational drug MNK-795 achieved the primary endpoint in a Phase 3 efficacy trial in the treatment of acute pain following a bunionectomy.

In the study, MNK-795 showed statistically significant http://www.4-traders.com/MALLINCKRODT-PLC-13450292/news/Mallinckrodt-PLC–Mallinckrodt-Pharmaceuticals-Announces-Positive-Phase-3-Efficacy-Results-for-MNK-17242621/

Share

This Biotech Has So Many Reasons to Be Liked

 Uncategorized  Comments Off on This Biotech Has So Many Reasons to Be Liked
Sep 062013
 

This Biotech Has So Many Reasons to Be Liked
Motley Fool
With promising mid-stage results, the drug is expected to do well in phase 3 evaluation for pancreatic cancer.

Positive phase 3 results will open the door to the lucrative pancreatic cancer market, on top of the myelofibrosis market that is expected to

READ ALL AT

http://www.fool.com/investing/general/2013/09/05/this-biotech-has-so-many-reasons-to-be-liked.aspx

Share

Oramed Submits Pre-IND Package to FDA for ORMD-0901 (oral exenatide)

 Uncategorized  Comments Off on Oramed Submits Pre-IND Package to FDA for ORMD-0901 (oral exenatide)
Sep 042013
 

Oramed Submits Pre-IND Package to FDA for ORMD-0901 (oral exenatide), an
MarketWatch
JERUSALEM, September 3, 2013 /PRNewswire via COMTEX/ — Oramed Pharmaceuticals Inc. (nasdaqcm:ORMP) (http://www.oramed.com), a developer of oral drug delivery systems, announced today that it has submitted a pre-Investigational New Drug capsule

http://www.marketwatch.com/story/oramed-submits-pre-ind-package-to-fda-for-ormd-0901-oral-exenatide-an-oral-glp-1-analog-for-the-treatment-of-type-2-diabetes-2013-09-03?reflink=MW_news_stmp

Share

DCGI asks Wockhardt, Ranbaxy to explain lapses

 companies  Comments Off on DCGI asks Wockhardt, Ranbaxy to explain lapses
Sep 022013
 

the-drug-regulator-is-now-awaiting-responses-from-the-companies-to-take-further-action

Indian drug makers Ranbaxy and Wockhardt have been issued a letter by the DCGI to explain deficiencies found at the company’s manufacturing units

Following an import alert by the US FDA, Indian drug maker Wockhardt has now been asked to explain the lapses at the company’s Aurangabad based manufacturing unit that was pulled up by the US drug regulator earlier this year Indian drug makers Ranbaxy and Wockhardt have been issued a letter by the DCGI to explain deficiencies found at the company’s manufacturing units
The Indian Drug Controller General of India (DCGI) has written a letter to the drug maker Wockhardt to explain the deficiencies found at its Aurangabad manufacturing unit. The FDA had issued an import alert to the drug maker earlier this year.
Read more at: http://www.biospectrumasia.com/biospectrum/regulatory/194552/dcgi-wockhardt-ranbaxy-explain-lapses#.UiQ6X6I3CSo

Share

Turmeric Extract 100% Effective At Preventing Type 2 Diabetes, ADA Journal Study Finds

 diabetes  Comments Off on Turmeric Extract 100% Effective At Preventing Type 2 Diabetes, ADA Journal Study Finds
Aug 312013
 

A remarkable human clinical study published in the journal Diabetes Care, the journal of the American Diabetes Association, revealed that turmeric extract was 100% successful at preventing prediabetic patients from becoming diabetic over the course of a 9-month intervention.[1]

Performed by Thailand researchers, the study’s primary object was to assess the efficacy of curcumin, the primary polyphenol in turmeric which gives the spice its golden hue, in delaying the development of type 2 diabetes mellitus (T2DM) in a prediabetic population.http://www.greenmedinfo.com/blog/turmeric-extract-100-effective-preventing-type-2-diabetes-ada-journal-study-finds

Share

Bladder Cancer Drug Pipeline Update 2013

 cancer  Comments Off on Bladder Cancer Drug Pipeline Update 2013
Aug 302013
 

 

Bladder Cancer Drug Pipeline Update 2013
Sacramento Bee
Pipeline Breakdown According to Number of Drugs Marketed# 10 Pre-registration# 1 Phase III# 4 Phase II# 45 Phase I# 26 Preclinical# 29 Suspended# 3 Ceased# 30 Note: You are able to sort and find drugs according to developmental stage from http://www.sacbee.com/2013/08/29/5691549/bladder-cancer-drug-pipeline-update.html

Share

Experimental Drug Shows Promise for Rare Genetic Disorder

 Uncategorized  Comments Off on Experimental Drug Shows Promise for Rare Genetic Disorder
Aug 302013
 

Transthyretin, or TTR for amyloidosis

THURSDAY Aug. 29, 2013 — A new medication appears to be highly effective in combating a heredity-based form of the organ-damaging genetic disorder known as amyloidosis, according to researchers.

Amyloidosis refers to a family of more than a dozen diseases in which different types of abnormal proteins called amyloids lodge in major organs and nerves. These amyloids build up to the point that they cause damage and, ultimately, organ failure.

read all at

http://www.drugs.com/news/experimental-shows-promise-rare-genetic-disorder-47059.html

 

Transthyretin (TTR) is a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine (T4) and retinol-binding protein bound to retinol. This is how transthyretin gained its name, transports thyroxine and retinol. The liver secretes transthyretin into the blood, and the choroid plexus secretes TTR into thecerebrospinal fluid.

TTR was originally called prealbumin[1] (or thyroxine-binding prealbumin) because it ran faster than albumin on electrophoresis gels.

Binding affinities

It functions in concert with two other thyroid hormone-binding proteins in the serum:

Protein Binding strength Plasma concentration
thyroxine-binding globulin (TBG) highest lowest
transthyretin (TTR) lower higher
albumin poorest much higher

In cerebrospinal fluid TTR is the primary carrier of T4. TTR also acts as a carrier ofretinol (vitamin A) through its association with retinol-binding protein (RBP) in the blood and the CSF. Less than 1% of TTR’s T4 binding sites are occupied in blood, which is taken advantage of below to prevent TTRs dissociation, misfolding and aggregation which leads to the degeneration of post-mitotic tissue.

Numerous other small molecules are known to bind in the thyroxine binding sites, including many natural products (such as resveratrol), drugs (Tafamidis,[2] or Vyndaqel, diflunisal,[3][4][5] flufenamic acid),[6] and toxins (PCB[7]).

Structure

TTR is a 55kDa homotetramer with a dimer of dimers quaternary structure that is synthesized in the liverchoroid plexus and retinal pigment epithelium for secretion into the bloodstream, cerebrospinal fluid and the eye, respectively. Each monomer is a 127-residue polypeptide rich in beta sheet structure. Association of two monomers via their edge beta-strands forms an extended beta sandwich. Further association of two of these dimers in a face-to-face fashion produces the homotetrameric structure and creates the two thyroxine binding sites per tetramer. This dimer-dimer interface, comprising the two T4 binding sites, is the weaker dimer-dimer interface and is the one the comes apart first in the process of tetramer dissociation.[8]

  1.  Prealbumin at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. a b Razavi H, Palaninathan SK, Powers ET, Wiseman RL, Purkey HE, Mohamedmohaideen NN, Deechongkit S, Chiang KP, Dendle MT, Sacchettini JC, Kelly JW (June 2003). “Benzoxazoles as transthyretin amyloid fibril inhibitors: synthesis, evaluation, and mechanism of action”. Angew. Chem. Int. Ed. Engl. 42 (24): 2758–61.doi:10.1002/anie.200351179PMID 12820260.
  3. ^ Sekijima Y, Dendle MA, Kelly JW (December 2006). “Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis”. Amyloid 13 (4): 236–49. doi:10.1080/13506120600960882.PMID 17107884.
  4. ^ Adamski-Werner SL, Palaninathan SK, Sacchettini JC, Kelly JW (January 2004). “Diflunisal analogues stabilize the native state of transthyretin. Potent inhibition of amyloidogenesis”. J. Med. Chem. 47 (2): 355–74. doi:10.1021/jm030347n.PMID 14711308.
  5. ^ Vilaro M, Arsequell G, Valencia G, Ballesteros A, Barluenga J, Nieto J, Planas A, Almeida R, Saraiva MJ (2007). “Reengineering TTR amyloid inhibition properties of diflunisal”. In Seldin DC, Skinner M, Berk JL, Connors LH. XIth International Symposium on Amyloidosis. Boca Raton: CRC.doi:10.1201/9781420043358.ch69ISBN 1-4200-4281-5.
  6. ^ Baures PW, Oza VB, Peterson SA, Kelly JW (July 1999). “Synthesis and evaluation of inhibitors of transthyretin amyloid formation based on the non-steroidal anti-inflammatory drug, flufenamic acid”. Bioorg. Med. Chem. 7 (7): 1339–47.doi:10.1016/S0968-0896(99)00066-8PMID 10465408.
  7. ^ Purkey HE, Palaninathan SK, Kent KC, Smith C, Safe SH, Sacchettini JC, Kelly JW (December 2004). “Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity”.Chem. Biol. 11 (12): 1719–28.doi:10.1016/j.chembiol.2004.10.009PMID 15610856.
  8. ^ Foss TR, Wiseman RL, Kelly JW (November 2005). “The pathway by which the tetrameric protein transthyretin dissociates”. Biochemistry 44 (47): 15525–33.doi:10.1021/bi051608tPMID 16300401.

 

Share

Semisynthetic Latrunculin Derivatives as Inhibitors of Metastatic Breast Cancer: Biological Evaluations, Preliminary Structure–Activity Relationship and Molecular Modeling Studies

 Uncategorized  Comments Off on Semisynthetic Latrunculin Derivatives as Inhibitors of Metastatic Breast Cancer: Biological Evaluations, Preliminary Structure–Activity Relationship and Molecular Modeling Studies
Aug 292013
 

Thumbnail image of graphical abstract

The microfilament cytoskeleton protein actin plays an important role in cell biology and affects cytokinesis, morphogenesis, and cell migration. These functions usually fail and become abnormal in cancer cells. The marine-derived macrolides latrunculins A and B, from the Red Sea sponge Negombata magnifica, are known to reversibly bind actin monomers, forming 1:1 stoichiometric complexes with G-actin, disrupting its polymerization. To identify novel therapeutic agents for effective treatment of metastatic breast cancer, several semisynthetic derivatives of latrunculin A with diverse steric, electrostatic, and hydrogen bond donor and acceptor properties were rationally prepared. Analogues were designed to modulate the binding affinity toward G-actin. Examples of these reactions are esterification, acetylation, and N-alkylation. Semisynthetic latrunculins were then tested for their ability to inhibit pyrene-conjugated actin polymerization, and subsequently assayed for their antiproliferative and anti-invasive properties against MCF7 and MDA-MB-231 cells using MTT and invasion assays, respectively.

Semisynthetic Latrunculin Derivatives as Inhibitors of Metastatic Breast Cancer: Biological Evaluations, Preliminary Structure–Activity Relationship and Molecular Modeling Studies (pages 274–285)

Mohammad A. Khanfar, Diaa T. A. Youssef and Khalid A. El Sayed

Article first published online: 30 DEC 2009 | DOI: 10.1002/cmdc.200900430

ChemMedChem

Volume 5, Issue 2, pages 274–285, February 1, 2010

http://onlinelibrary.wiley.com/doi/10.1002/cmdc.200900430/abstract

Negombata magnifica, a Red Sea sponge (background), is the natural source of latrunculin A. A series of latrunculin A derivatives were synthesized and tested for their ability to inhibit G-actin polymerization and breast cancer cell proliferation and invasion. Molecular modeling simulations (inset) were applied to improve the understanding of the SAR of latrunculins.

 

Share

Study shows flavonoid Luteolin can block cancer cell signaling

 Uncategorized  Comments Off on Study shows flavonoid Luteolin can block cancer cell signaling
Aug 232013
 

Luteolin_rich_vegetable

Luteolin, a flavonoid compound commonly found in fruit and vegetables, has been found to be able to surppress the activity of cell signaling pathways (IGF and PI3K) that play key roles in growth of cancer cells.

LUTEOLIN

The study, published in BioMed Central’s open access journal BMC Gastroenterology, suggested the possibility of developing novel therapies based on the plant flavonoid Luteolin against colon cancer, the second most frequent cause of cancer-related death in the Western World. Colon cancer cells have elevated levels of IGF-II compared to normal colon tissues.

Luteolin, commonly found in green peppers, carrots, olive oil, rosemary, peppermint, oranges and celery, has been shown by preclinical studies to have anti-inflammatory, anti-oxidant, antimicrobial, and anticancer activities. Earlier studies have found that luteolin could inhibit angiogenesis, induce apoptosis and affect carcinogenesis in animal models, suggesting the possibility to use this flavonoid as cancer chemopreventive and chemotherapeutic agent.

A group of Korean scientist performed studies that show that luteolin inhibits the secretion of IGF-II by colon cancer cells and within two hours decreased the amount of receptor (IGF-IR) precursor protein. Luteolin also reduced the amount of active receptor (measured by IGF-I dependent phosphorylation).
It is noted in the publication that luteolin “downregulates the activation of the PI3K/Akt and ERK1/2 pathways via a reduction in IGF-IR signaling in HT-29 cells; this may be one of the mechanisms responsible for the observed luteolin-induced apoptosis and cell cycle arrest”.
Colon cancer cells have elevated levels of IGF-II compared to normal colon tissues. It is thought that this is part of the mechanism driving uncontrolled cell division and cancer growth.

Prof Jung Han Yoon Park, the corresponding author of the publication, says “Our study, showing that luteolin interferes with cell signaling in colon cancer cells, is a step forward in understanding how this flavonoid works. A fuller understanding of the in vivo results is essential to determine how it might be developed into an effective chemopreventive agent”.

 

Luteolin is a yellow crystalline compound. It is a flavonoid; to be specific, it is one of the more common flavones.[1] From preliminary research, it is thought to play a role in the human body possibly as an antioxidant, a free radical scavenger, a promoter ofcarbohydrate metabolism, or an immune system modulator.[citation needed] If applicable to the human condition, these characteristics may inhibit cancer mechanisms. Basic research results indicate luteolin as an anti-inflammatory agent,[2] with other potential effects on septic shock.[citation needed] It has been suggested for multiple sclerosis on the basis of in vitro work.[3]

Luteolin acts as a monoamine transporter activator, and is one of the few chemicals demonstrated to possess this property.[4]

Natural occurrences

Luteolin can be found in Terminalia chebula. It is most often found in leaves, but it is also seen in rinds, barksclover blossom, and ragweed pollen.[1] It has also been isolated from Salvia tomentosa.[5]

In food

Dietary sources include celerygreen pepperparsleythyme, dandelion, perilla,chamomile tea, carrots, olive oil, peppermint, rosemary, navel oranges, and oregano.[6][7]

It can also be found in the seeds of the palm Aiphanes aculeata.[8]

 

  1. Mann, John (1992). Secondary Metabolism (2nd ed.). Oxford, UK: Oxford University Press. pp. 279–280. ISBN 0-19-855529-6.
  2. Johnson; Kelley, KW; Johnson, RW (May 2008). “Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1”Proc. Natl. Acad. Sci. U.S.A. 105 (21): 7534–9. doi:10.1073/pnas.0802865105PMC 2396685.PMID 18490655.
  3.  Theoharides (2009). “Luteolin as a Therapeutic Option for Multiple Sclerosis”Journal of Neuroinflammation 6 (1): 29.doi:10.1186/1742-2094-6-29PMC 2768692PMID 19825165.
  4.  Zhao, G; Qin, GW; Wang, J; Chu, WJ; Guo, LH (2010). “Functional activation of monoamine transporters by luteolin and apigenin isolated from the fruit of Perilla frutescens (L.) Britt”. Neurochemistry international 56 (1): 168–76. doi:10.1016/j.neuint.2009.09.015.PMID 19815045.
  5. A. Ulubelen, M. Miski, P. Neuman, and T. J. Mabry (1979). “Flavonoids of Salvia tomentosa (Labiatae)”. Journal of Natural Products 42(4): 261–3. doi:10.1021/np50003a002.
  6. Kayoko Shimoi, Hisae Okada, Michiyo Furugori, Toshinao Goda, Sachiko Takase, Masayuki Suzuki, Yukihiko Hara, Hiroyo Yamamoto, Naohide Kinae (1998). “Intestinal absorption of luteolin and luteolin 7-O-[beta]-glucoside in rats and humans”. FEBS Letters 438 (3): 220–4. doi:10.1016/S0014-5793(98)01304-0PMID 9827549.
  7. López-Lázaro M. (2009). “Distribution and biological activities of the flavonoid luteolin“. Mini Rev Med Chem. 9 (1): 31–59.doi:10.2174/138955709787001712PMID 19149659.
  8. Lee, D; Cuendet, M; Vigo, JS; Graham, JG; Cabieses, F; Fong, HH; Pezzuto, JM; Kinghorn, AD (2001). “A novel cyclooxygenase-inhibitory stilbenolignan from the seeds of Aiphanes aculeata”. Organic letters 3 (14): 2169–71. PMID 11440571.

Share
Follow

Get every new post on this blog delivered to your Inbox.

Join other followers: