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Suramin
A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.
A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. Suramin is manufactured by Bayer in Germany as Germanin®.
Also known as: Naphuride, Germanin, Naganol, Belganyl, Fourneau, Farma, Antrypol, Suramine, Naganin
8,8′-{Carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]}di(1,3,5-naphthalenetrisulfonic acid) …FREE FORM
8,8′-[Ureylenebis[m-phenylenecarbonylimino(4-methyl-m-phenylene)carbonylimino]]di(1,3,5-naphthalenetrisulfonic acid) hexasodium salt
CAS 145-63-1 FREE FORM
129-46-4 of hexa sodium
LAUNCHED 1940 BAYER
| Formula | C51H40N6O23S6 |
|---|---|
| Mol. mass | 1297.29 |
The molecular formula of suramin is C51H34N6O23S6. It is a symmetric molecule in the center of which lies urea, NH-CO-NH. Suramin contains eightbenzene rings, four of which are fused in pairs (naphthalene), four amide groups in addition to the one of urea and six sulfonate groups. When given as drug it usually contains six sodium ions that form a salt with the six sulfonate groups.
Suramin is a drug developed by Oskar Dressel and Richard Kothe of Bayer, Germany in 1916, and is still sold by Bayer under the brand nameGermanin.
Suramin sodium is a heparanase inhibitor that was first launched in 1940 by Bayer under the brand name Antrypol for the treatment of helminthic infection. It was later launched by Bayer for the treatment of trypanosomiasis (African sleeping sickness).
More recently, the product has entered early clinical development at Ohio State University for the treatment of platinum-pretreated patients with stage IIIB/IV non-small cell lung cancer, in combination with docetaxel or gemcitabine.
The National Cancer Institute (NCI) is conducting phase II clinical studies for the treatment of glioblastoma multiforme and for the treatment of adrenocortical carcinoma.
According to the National Cancer Institute there are no active clinical trials (as of April 1, 2008). Completed and closed clinical trials are listed here:[1]
In addition to Germanin, the National Cancer Institute also lists the following “Foreign brand names”: 309 F or 309 Fourneau,[1] Bayer 205, Moranyl, Naganin, Naganine.
It is used for treatment of human sleeping sickness caused by trypanosomes.[2]
Also, suramin as treatment for autism is being evaluated. [5]
Kidney damage and exfoliative dermatitis occur less commonly.
Suramin has been applied clinically to HIV/AIDS patients resulting in a significant number of fatal occurrences and as a result the application of this molecule was abandoned for this condition. http://www.ncbi.nlm.nih.gov/pubmed/3548350
Suramin is also used in research as a broad-spectrum antagonist of P2 receptors[6][7] and agonist of Ryanodine receptors.[8]
![ChemSpider 2D Image | 8,8'-{Carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]}di(1,3,5-naphthalenetrisulfonic acid) | C51H40N6O23S6](https://images-blogger-opensocial.googleusercontent.com/gadgets/proxy?url=http%3A%2F%2Fwww.chemspider.com%2FImagesHandler.ashx%3Fid%3D5168%26w%3D200%26h%3D200&container=blogger&gadget=a&rewriteMime=image%2F*)
Its effect on telomerase has been investigated.[9]
It may have some activity against RNA viruses.[10]
In addition to antagonism of P2 receptors, Suramin inhibits the acitivation of heterotrimeric G proteins in a variety of other GPCRs with varying potency. It prevents the association of heteromeric G proteins and therefore the receptors Guanine exchange functionality (GEF). With this blockade the GDP will not release from the Gα subunit so it can not be replaced by a GTP and become activated. This has the effect of blocking downstream G protein mediated signaling of various GPCR proteins including Rhodopsin, the A1 Adenosine receptor, and the D2 dopamine receptor.[11]
A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. Suramin is manufactured by Bayer in Germany as Germanin®.
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InCl3-catalysed synthesis of 2-aryl quinazolin-4(3H)-ones and 5-aryl pyrazolo[4,3-d]pyrimidin-7(6H)-ones and their evaluation as potential anticancer agents. |
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Identification of a sirtuin 3 inhibitor that displays selectivity over sirtuin 1 and 2. |
European journal of medicinal chemistry |
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Inhibition of the human deacylase Sirtuin 5 by the indole GW5074. |
Bioorganic & medicinal chemistry letters |
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SURAMIN
Enterovirus-71 (EV71) is one of the major causative reagents for hand-foot-and-mouth disease. In particular, EV71 causes severe central nervous system infections and leads to numerous dead cases. Although several inactivated whole-virus vaccines have entered in clinical trials, no antiviral agent has been provided for clinical therapy. In the present work, we screened our compound library and identified that suramin, which has been clinically used to treat variable diseases, could inhibit EV71 proliferation with an IC50 value of 40μM. We further revealed that suramin could block the attachment of EV71 to host cells to regulate the early stage of EV71 infection, as well as affected other steps of EV71 life cycle. Our results are helpful to understand the mechanism for EV71 life cycle and provide a potential for the usage of an approved drug, suramin, as the antiviral against EV71 infection.
Synonyms
Suramin Sodium, is an anticancer agent with a wide variety of activities.
Recently suramin was shown to inhibit FSH binding to its receptor (Daugherty, R. L.; Cockett, A. T. K.; Schoen, S. R. and Sluss, P. M. “Suramin inhibits gonadotropon action in rat testis: implications for treatment of advanced prostate cancer” J. Urol. 1992, 147, 727-732).
This activity causes, at least in part, the decrease in testosterone production seen in rats and humans that were administered suramin(Danesi, R.; La Rocca, R. V.; Cooper, M. R.; Ricciardi, M. P.; Pellegrini, A.; Soldani, P.; Kragel, P. J.; Paparelli, A.; Del Tacca, M.; Myers, C. E, “Clinical and experimental evidence of inhibition of testosterone production by suramin.” J. Clin. Endocrinol. Metab. 1996, 81, 2238-2246).
Suramin is the only non-peptidic small molecule that has been reported to be an FSH receptor binding antagonist.
Suramin is 8,8′ – (carbonylbis(imino-3,1-phenylenecarbonylimino (4-methyl-3,1-phenylene) carbonylimino)) bis-1,3 ,5-naphthalenetrisulfonic acid (GB Patent No. 224849). This polyanionic compound has been used for many decades as a prophylactic and therapeutic agent for try- panosomiasis. It was subsequently shown that suramin is able to block the activity of a variety of proteins like cellular and viral enzymes and growth factors (Mitsuya, M. et al. Science 226 : 172 (1984), Hosang, M. J. Cell. Biochem. 29 : 265 (1985), De Clercq, E. Cancer Lett. 8 : 9 (1979)).
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5-32-1977 |
Complement inhibitors |
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Aromatic amidines as antiviral agents in animals |
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5-4-1977 |
Complement inhibitors |
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5-4-1977 |
Complement inhibitors |
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4-27-1977 |
Cyclodextrin sulfate salts as complement inhibitors |
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4-20-1977 |
Ureylenebis methyl-phenylene-carbonyl-bis-dihydro-2-oxo-naphthoxazine disultonic acids |
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3-30-1977 |
Water treatment for controlling the growth of algae employing biguanides |
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3-2-1977 |
Isoxazole substituted nitroimidazoles |
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2-16-1977 |
Amidophenyl-azo-naphthalenesulfonic complement inhibitors and method of use thereof |
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2-9-1977 |
Complement inhibitors |
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2-10-2011 |
MODULATION OF HUMAN MAST CELL ACTIVATION MODULATION OF HUMAN MAST CELL ACTIVATION |
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Admixtures for inorganic binders based on a hydrogenated disaccharide, inorganic binders containing these admixtures and process for their preparation Admixtures for inorganic binders based on a hydrogenated disaccharide, inorganic binders containing these admixtures and process for their preparation |
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THERAPEUTIC INHIBITORS OF VASCULAR SMOOTH MUSCLE CELLS |
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APPARATUS FOR USING ELECTROPORATION MEDIATED DELIVERY OF DRUGS AND GENES |
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4-8-2010 |
PREPARATION AND USE OF SULFATED OLIGOSACCHARIDES |
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10-29-2009 |
THERAPEUTIC INHIBITOR OF VASCULAR SMOOTH MUSCLE CELLS THERAPEUTIC INHIBITOR OF VASCULAR SMOOTH MUSCLE CELLS |
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8-20-2009 |
METHOD OF MAKING MINERAL FIBRES METHOD OF MAKING MINERAL FIBRES |
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6-25-2009 |
OXYGEN-FUEL BOOST REFORMER PROCESS AND APPARATUS |
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4-23-2009 |
METHODS OF TREATING VASCULAR DISEASE WITH TNF ANTAGONISTS METHODS OF TREATING VASCULAR DISEASE WITH TNF ANTAGONISTS |
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3-26-2009 |
COPOLYMER COMPOSITIONS FOR ORAL DELIVERY |
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5-3-1978 |
1,3,5- Or 1,3,6-naphthalenetriyltris(sulfonylimino)aryl acids and salts |
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3-22-1978 |
Nitroimidazoles |
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2-15-1978 |
Treatment of rheumatoid arthritis and related diseases |
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1-4-1978 |
AROMATIC AMIDINES AS ANTIVIRAL AGENTS IN ANIMALS |
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1-4-1978 |
Malto-dextrin poly(H-)sulfates |
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12-14-1977 |
Disazo compounds useful as complement inhibitors |
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12-7-1977 |
Bis-substituted naphthalene-azo phenyleneazo-stilbene-disulfonic and naphthalene-sulfonic acid |
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9-28-1977 |
UREIDOPHENYLENEBIS(CARBONYLIMINO)DINAPHTHALENETRISULFONIC ACID COMPOUNDS |
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9-21-1977 |
Substituted bisnaphthylazo diphenyl ureido complement inhibitors |
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9-7-1977 |
Substituted-hydroxy-naphthalenedisulfonic acid compounds |
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1-12-1977 |
Complement inhibitors |
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12-22-1976 |
Complement inhibitors |
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10-13-1976 |
Complement inhibitors |
| EP0183352A2 * | Sep 27, 1985 | Jun 4, 1986 | THE UNITED STATES OF AMERICA as represented by the Secretary United States Department of Commerce | Use of suramin for clinical treatment of infection with any of the members of the family of human-t-cell leukemia (htvl) viruses including lymphadenopathy virus (lav) |
| EP0205077A2 * | Jun 3, 1986 | Dec 17, 1986 | Bayer Ag | Suramin sodium for use as an immunostimulant |
| EP0515523A1 * | Feb 13, 1991 | Dec 2, 1992 | THE UNITED STATES OF AMERICA as represented by the Secretary United States Department of Commerce | Use of suramin to treat rheumatologic diseases |
| EP0755254A1 * | Mar 24, 1995 | Jan 29, 1997 | The Trustees Of The University Of Pennsylvania | Prevention and treatment of ischemia-reperfusion and endotoxin-related injury using adenosine and purino receptor antagonists |
| EP1460087A1 * | Feb 17, 1997 | Sep 22, 2004 | The Kennedy Institute Of Rheumatology | Methods of treating vascular disease with TNF antagonists |
| EP1940376A2 * | Oct 3, 2006 | Jul 9, 2008 | Rottapharm S.P.A. | Use of neboglamine in the treatment of toxicodependency |
| EP1945204A2 * | Oct 27, 2006 | Jul 23, 2008 | Brane Discovery S.R.L. | V-atpase inhibitors for use in the treatment of septic shock |
| US5453444 * | Oct 6, 1994 | Sep 26, 1995 | Otsuka Pharmaceutical Co., Ltd. | Method to mitigate or eliminate weight loss |
| US5534539 * | Jun 12, 1995 | Jul 9, 1996 | Farmitalia Carlo Erba S.R.L. | Biologically active ureido derivatives useful as anit-metastic agenst |
| US5596105 * | Jan 13, 1995 | Jan 21, 1997 | Farmitalia Carlo Erba S.R.L. | Therapeutically active naphthalenesulfonic pyrrolecarboxamido derivatives |
| US7476693 | Mar 26, 2003 | Jan 13, 2009 | Eastern Virginia Medical School | Suramin and derivatives thereof as topical microbicide and contraceptive |
| US7608262 | Feb 16, 1996 | Oct 27, 2009 | The Kennedy Institute Of Rheumatology | Methods of preventing or treating thrombosis with tumor necrosis factor antagonists |
| US8552064 | Dec 19, 2008 | Oct 8, 2013 | Eastern Virginia Medical School | Suramin and derivatives thereof as topical microbicide and contraceptive |
| WO1994008574A1 * | Oct 12, 1993 | Apr 28, 1994 | Otsuka America Pharmaceutical | Treatment of cachexia and inhibition of il-6 activity |
| WO1994010990A1 * | Nov 12, 1993 | May 26, 1994 | British Bio Technology | Inhibition of tnf production |
| WO1997030088A2 * | Feb 17, 1997 | Aug 21, 1997 | Kennedy Inst Of Rheumatology | Methods of treating vascular disease with tnf antagonists |
| WO2004113920A1 * | Jun 18, 2004 | Dec 29, 2004 | Babon Jeff James | Screening method for substances binding to merozoite surface protein-1/42 |
| WO2008138943A2 * | May 14, 2008 | Nov 20, 2008 | Mara Galli | Prophylactic and therapeutic use of sirtuin inhibitors in tnf-alpha mediated pathologies |
| WO2009137471A2 * | May 5, 2009 | Nov 12, 2009 | University Of Miami | Azo dye related small molecule modulators of protein-protein interactions |
| WO2010016628A1 * | Jul 10, 2009 | Feb 11, 2010 | Sammy Opiyo | Conjugated suramin amino compounds for medical conditions |
| WO2012159107A1 * | May 21, 2012 | Nov 22, 2012 | Rhode Island Hospital | Inhibition of renal fibrosis |
Title: Suramin Sodium
CAS Registry Number: 129-46-4
CAS Name: 8,8¢-[Carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]]bis-1,3,5-naphthalenetrisulfonic acid hexasodium salt
Additional Names: hexasodium sym-bis(m-aminobenzoyl-m-amino-p-methylbenzoyl-1-naphthylamino-4,6,8-trisulfonate) carbamide
Manufacturers’ Codes: Bayer 205; Fourneau 309
Trademarks: Antrypol (AstraZeneca); Germanin (Bayer); Moranyl (Specia); Naganol; Naphuride
Molecular Formula: C51H34N6Na6O23S6
Molecular Weight: 1429.17
Percent Composition: C 42.86%, H 2.40%, N 5.88%, Na 9.65%, O 25.75%, S 13.46%
Literature References: Discovered in 1917 by O. Dressel and R. Kothe: J. Dressel, J. Chem. Educ. 38, 620 (1961). Prepn: E. Fourneau et al., Compt. Rend. 178, 675 (1924); J. Trefouel, E. Fourneau, GB 224849 (1923); B. Heymann, Angew. Chem. 37, 585 (1924). Pharmacology, toxicology and clinical antiparasitic activity: F. Hawking, Adv. Pharmacol. Chemother. 15, 289-322 (1978). Inhibition of reverse transcriptase in vitro: E. De Clercq, Cancer Lett. 8, 9 (1979); vs HIV: H. Mitsuya et al., Science 226, 172 (1984). HPLC determn in plasma: R. W. Klecker, J. M. Collins, J. Liq. Chromatogr. 8, 1685 (1985). Pharmacokinetics: J. M. Collins et al., J. Clin. Pharmacol. 26, 22 (1986). Pharmacology and virustatic effect in AIDS: S. Broder et al., Lancet 2, 627 (1985); A. M. Levine et al., Ann. Intern. Med. 105, 32 (1986). Clinical trial in onchocerciasis: H. Schultz-Key et al., Trop. Med. Parasitol. 36, 244 (1985); in prostate cancer: C. Myers et al., J. Clin. Oncol. 10, 881 (1992). Review: Olenick in Antibiotics vol. 3,J. W. Corcoran, F. E. Hahn, Eds. (Springer-Verlag, New York, 1975) pp 699-703; R. La Rocca et al., Cancer Cells 2, 106-115 (1990).
Properties: White or slightly pink or cream-colored powder. Slightly bitter taste. Hygroscopic. Freely sol in water, in physiological saline; sparingly sol in 95% alcohol. Insol in benzene, ether, petr ether, chloroform. Aq solns are neutral to litmus. LD50 in mice (mg/kg): ~620 i.v. (Hawking).
Toxicity data: LD50 in mice (mg/kg): ~620 i.v. (Hawking)
Therap-Cat: Anthelmintic (Nematodes); antiprotozoal (Trypanosoma).
Therap-Cat-Vet: Antiprotozoal (Trypanosoma).
Keywords: Anthelmintic (Nematodes); Antiprotozoal (Trypanosoma); Reverse Transcriptase Inhibitor.
THANKS AND REGARD’S
DR ANTHONY MELVIN CRASTO Ph.D
GLENMARK SCIENTIST , NAVIMUMBAI, INDIA
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I was paralysed in dec2007, Posts dedicated to my family, my organisation Glenmark, Your readership keeps me going and brings smiles to my family
Author and Curator: Larry H. Bernstein, MD, FCAP
This concludes the series on metabolomics, a rapidly developing science that is interconnected with a group termed – OMICS: proteomics, transcriptomics, genomics, and metabolomics. This chapter is most representative of the many important studies being done in the field, which ranges most widely because it has opened doors into nutrition and nutritional supplements, plant biochemistry, agricultural crops and breeding, animal breeding, worldwide malnutrition, diabetes, cancer, neurosciences, circulatory, respiratory, and musculosletal disorders, infectious diseases and immune system disorders. Obviously, it is not possible to cover the full range of activity, but metabolomics is most comprehensive in exploring the full range of metabolic changes that occur in health during the full age range from development to the geriatric years. It can be integrated well with gene expression, proteomics studies, and epidemiological investigations.
The subchapters are given here:
7.1 Extracellular evaluation of intracellular flux in yeast cells
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Flow Chemistry test facility in India
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Plantrix® Industrial Flow Chemistry Test Facility in India
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Enrollment Begins of First Patient in Phase II Vatelizumab Trial in Relapsing Remitting Multiple Sclerosis
Glenmark outlicensed Vatelizumab (GBR 500) to Sanofi for all indications in 2011
Mumbai – India, November 4, 2014: Glenmark announced today enrollment of the first patient in a multicenter Phase II clinical trial to evaluate Genzyme’s investigational infusion therapy vatelizumab in patients with relapsing remitting multiple sclerosis (RRMS). The trial, called EMPIRE, is designed to assess the efficacy of vatelizumab vs. placebo in RRMS patients. The safety, tolerability and pharmacokinetics of vatelizumab will also be assessed.
read at
The mechanism of action of vatelizumab, which is developed in a collaboration between Glenmark Pharmaceuticals and Genzyme, is not yet fully understood. However, the researchers believe that it will be able to block VLA-2 on activated immune cells, which may enable the interference with collagen-binding in areas of inflammation, as well as leading to the reduction of inflammatory cascade associated with MS.
“We are excited about the commencement of this trial and are pleased with the continued progress of our partnership with Sanofi/Genzyme,” said the President of Biologics and Chief Scientific Officer of Glenmark Pharmaceuticals Ltd., Michael Buschle. EMPIRE, which will be conducted for 12 weeks, is a global phase 2a/2b double-blind, randomized, placebo-controlled study that will study the efficacy, safety, and dose-response of vatelizumab in 168 patients with active RRMS at55 sites in ten different countries.
Vatelizumab is an immunomodulator. It binds to integrin alpha 2.[1]
| Company | Glenmark Pharmaceuticals Ltd. |
| Description | mAb against integrin alpha(2) (VLA-2; CD49B) |
| Molecular Target | Integrin alpha(2) (VLA-2) (CD49B) |
| Mechanism of Action | Antibody |
| Therapeutic Modality | Biologic: Antibody |
| Latest Stage of Development | Phase I/II |
| Standard Indication | Inflammatory bowel disease (IBD) |
| Indication Details | Treat inflammatory bowel disease (IBD); Treat ulcerative colitis (UC) |
| Regulatory Designation | |
| Partner |
Beyond Meds: Alternatives to Psychiatry I’m reposting this because I’ve been going through another backbend stage and I thought of this post from a while back. I like to help people see how easy yoga can be. You can start with something as simple as this and see where it takes you. Being a yogi … Continue reading
Author and Curator: Larry H. Bernstein, MD, FCAP
Adieu, adieu, adieu …
Sound of Music
Snoopy – Charlie happiness
This work has been a coming to terms with my scientific and medical end of career balancing in a difficult time after retiring, but it has been rewarding. In the clinical laboratories, radiology, anesthesiology, and in pharmacy, there has been some significant progress in support of surgical, gynecological, developmental, medical practices, and even neuroscience directed disciplines, as well as epidemiology over a period of half a century. Even then, cancer and neurological diseases have been most difficult because the scientific basic research has either not yet uncovered a framework, or because that framework has proved to be multidimensional. In the clinical laboratory sciences, there has been enormous progress in instrumental analysis, with the recent opening of molecular methods not yet prepared for routine clinical…
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19 Nov 2012
Caterpillar fungi (Cordyceps) are rare parasites found on hibernating caterpillars in the mountains of Tibet. For centuries they have been highly prized as a traditional Chinese medicine – just a small amount can fetch hundreds of pounds.
Scientists at The University of Nottingham have been studying how this fungus could work by studying cordycepin, one of the drugs found in these mushrooms. They have already discovered that cordycepin has potential as a cancer drug. Their new work indicates that it could also have anti-inflammatory characteristics with the potential to help sufferers of asthma, rheumatoid arthritis, renal failure and stroke damage.
The research, published today in the academic journal RNA, was led by Dr Cornelia de Moor in the School of Pharmacy. It shows that cordycepin reduces inflammatory gene products in airway smooth muscle cells – the cells that contract during an asthma attack.
Several studies have suggested…
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K.R. Knudsen, J. Holden, S.V. Ley and M. Ladlow, Adv. Syn. Cat. 2007, 349, 535-538.
http://onlinelibrary.wiley.com/doi/10.1002/adsc.200600558/abstract
A versatile, fully automated flow hydrogenator has been developed that is able to perform sequential flow optimisation experiments, flow library hydrogenation, or iterative scale-up hydrogenation. The behaviour of a palladium catalyst in effecting removal of O-benzyl and N-benzyloxycarbonyl protecting groups has been investigated. Significant observations relating to maintaining optimal throughput are reported. A small library of peptidic derivatives has been deprotected in high yield and purity.
System configuration:
The system used was configured from a Gilson liquid handler (233XL), driven with a 10 mL
syringe pump (402). The syringe pump was connected to the sampling needle via a 2-way 6
position switching valve. This single channel liquid handler was used to perform both substrate
manipulation and fraction collection. The liquid handler was connected via a 2-way 6 position
injection valve to a Thales H-CubeTM flow hydrogenator driven with a KnauerTM A120 high
pressure pump. The collection vials were housed in specially designed gas tight blocks (2 x 7)
which were fitted with PTFA seals to enable penetration by the liquid handler needle, and
continuously purged with nitrogen in order to dilute and vent excess hydrogen safely. The
hardware was controlled using a single graphic user interface (HydroMateTM, Figure 2) which
utilised either RS232 or GSIOC connectivity to interface with the Thales and Gilson devices
respectively. Throughout 30 mm, 4 mm id 10% Pd/C catalyst cartridges (CatCartTM) were used
in conjunction with a 5 mL sample injection loop, although larger cartridges are also available.
The control software exploits software ‘wizards’ to assist the user in compiling a sequence of
optimisation experiments, or alternatively permits the implementation of a series of repetitive
experiments for either: (i) catalyst evaluation, (ii) reaction optimisation, (iii) compound library
synthesis, or (iv) as part of an automated, unattended scale up campaign (Figure 1). Experiments
may be devised with variations in scale, temperature, flow rate, and pressure in addition to
periodicity of fraction collection.
Analysis: RP-HPLC was run on a Hewlett Packard 1050 instrument. Column: Supelcosilä
ABZ+
PLUS column, 3.3 cm, 4.6 mm f, 3 mm. Eluent: A: water, 0.1% TFA, B: acetonitrile 95%,
water 5%, TFA 0.05%. Gradient: 10 to 95% B in A (1 mL min-1
) over 8 min. Detection: UV
(diode array detector).
A Microcapillary Flow Disc (MFD) Reactor for Organic Synthesis,
C.H. Hornung, M.R. Mackley, I.R. Baxendale and S.V. Ley and, Org. Proc. Res. Dev., 2007, 11, 399-405.
http://pubs.acs.org/doi/abs/10.1021/op700015f
This paper reports proof of concept, development, and trials for a novel plastic microcapillary flow disc (MFD) reactor. The MFD was constructed from a flexible, plastic microcapillary film (MCF), comprising parallel capillary channels with diameters in the range of 80−250 μm. MCFs were wound into spirals and heat treated to form solid discs, which were then capable of carrying out continuous flow reactions at elevated temperatures and pressures and with a controlled residence time. Three reaction schemes were conducted in the system, namely the synthesis of oxazoles, the formation of an allyl-ether, and a Diels−Alder reaction. Reaction scales of up to four kilograms per day could be achieved. The potential benefits of the MFD technology are compared against those of other reactor geometries including both conventional lab-scale and other microscale devices.
Continuous Flow Ligand-Free Heck Reactions Using Monolithic Pd[0] Nanoclusters
N. Nikbin, M. Ladlow, S.V. Ley, Org. Proc. Res. Dev., 2007, 11, 458-462.
http://pubs.acs.org/doi/abs/10.1021/op7000436
Flow-through reactor setup.
An automated reactor has been developed for performing ligand-free Heck reactions in continuous flow mode. The reactor utilises a monolithic reactor cartridge derivatised with Pd(0) nanoparticles in-line with a scavenging cartridge containing Quadrapure-TU to efficiently capture palladium residues and thereby afford Heck products directly in high purity.
New Drug Approvals 