About ERIX
EiRx Therapeutics is a specialist provider of pre-clinical therapeutics to the pharmaceutical industry. Our unique scientific expertise and knowledge in the field of Apoptosis provide a sound base to discover and develop new medicines that will safely and selectively repair this natural process in disease. The potential benefits from these new medicines are enormous, since as many as 70% of all human disease have some defect in the control of Apoptosis.
Apoptosis - the biological process that determines whether cells in our bodies live or die...
http://www.eirx.com/index.html

Purchased some of these on the strength of the PROGRESS UPDATE looks promising.
http://moneyam.uk-wire.com/cgi-bin/articles/200603200701130254A.html

ERX interview with John Pool
http://www.wallstreetreporter.com/interview.php?id=18589&player=real
Latest News
CANCER COLLABORATION WITH BIOMERIEUX SA
http://moneyam.uk-wire.com/cgi-bin/articles/200607120700230534G.html
Biomerieux Web Site
http://www.biomerieux.com/servlet/srt/bio/portail/home
ABOUT ERX Focus Of The Month
http://www.billamag.net/focus-document-text.asp?FocusTextID=1
ERX pdf filehttp://www.eirx.com/eirx_heading_images/Yokohama2005.pdf
19/09/2006 A 50% reduction in breast tumour volume size seen with Eirx lead molecule in animal studies
http://moneyam.uk-wire.com/cgi-bin/articles/200609190700171175J.html

Past and present collaborative partners include:

* bioMieux SA
* Almac Diagnostics Ltd
* Merck & Co, Ltd
* Biofocus plc
* MGI Pharmaceuticals, Inc
* OSI Pharmaceuticals, Inc
* Sareum plc
* Regen Therapeutics plc
* SR Pharma plc

and here is the new patent

http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2007017678&F=0

Description of WO2007017678



[0001] PYRAZOLO(1 ,5-A) PYRAMIDINE COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to certain pyrazolo[1 ,5-a]pyrimidine compounds, to processes for their preparation, compositions comprising them and methoda of using them. Novel screening methods are also provided.

[0004] BACKGROUND AND PRIOR ART

[0005] Apoptosis is a genetically regulated process of cell suicide that allows for the removal of unneeded, senescent or infected cells from the body while preserving the integrity and architecture of surrounding tissue. Whereas mitosis is responsible for the generation of new cells, apoptosis in contrast is responsible for removing the cells. It is this delicate balance of mitosis versus apoptosis that maintains tissue homeostasis.

[0006] Apoptotic pathways can be sub-divided into two categories, either the extrinsic apoptotic signals which are initiated on the outside of the cell by ligand engagement of cell surface receptors such as Fas and TNF receptors, and/ or the intrinsic pathways activated by signals emanating from cellular damage sensors (e.g. p53) or developmental cues. Although the pathways activated by extrinsic and intrinsic signals can overlap to some extent, receptor ligation (via an extrinsic signal) typically leads to recruitment of adapter proteins that promote caspase oligomerization and auto-processing

[0007] For example, following Fas ligand binding to the Fas receptor, the death signal is transmitted through conformational changes in preformed receptor clusters, resulting in the recruitment of the adaptor protein FADD (Fas-associated death-domain protein) through a DD-DD interaction. Once bound to Fas to form the death-inducing signalling complex, FADD then binds to the prodomain of caspase-8, which results in autoactivation of caspase-8 by proteolytic processing leading to cellular destruction {reviewed in Murphy et al Curr. Opin Pharm. 2003, 3:412-419).

[0008] In contrast, intrinsic signals usually operate by triggering the release of proteins from the mitochondria to the cytosol. Most notable among these is cytochrome c; binding of cytochrome c to a central apoptotic regulator, Apaf-1 , promotes oligomerization of Apaf-1 and, in a reaction requiring the ATPase activity of Apaf-1 , oligomerization and activation of caspase 9). Caspase 9 subsequently activates effector caspases such as 3, 6, and 7 and cellular destruction ensues (reviewed in Johnson & Jarvis 2004, Apoptosis.;9(4):423-7).

[0009] This targeted cell destruction is critical both in physiological contexts as well as pathological states. Apoptosis is the normal physiological response to many stimuli, including irreparable DNA damage. Various diseases evolve because of hyperactivation (neurodegenerative diseases, immunodeficiency, ischaemia-reperfusion injury) or suppression of programmed cell death (cancer, autoimmune disorders).

[0010] In cancer, the balance between mitosis and programmed cell death is disturbed, and defects in apoptotic pathways allow cells with genetic abnormalities to survive. The role of apoptosis in the genesis and progression of cancer has been well documented (e.g. Reed JC, 1999; J. Clin Oncol.17(9), 2941). Failure in normal apoptosis pathways contribute to carcinogenesis by creating a permissive environment for genetic instability and accumulation of gene mutations, promoting resistance to immune-based destruction, allowing disseverance of cell cycle checkpoints that would normally induce apoptosis, facilitating growth factor/hormone-independent cell survival, supporting anchorage- independent survival during metastasis, reducing dependence on oxygen and nutrients, and conferring resistance to cytotoxic anticancer drugs and radiation. Indeed, studies of colon specimens harvested at various points along the transformation of colorectal epithelium to carcinomas demonstrated a progressive inhibition of apoptosis (Bedi et al, 1995, Cancer Res. ;55(9):1811-6.)

[0011] COLON CANCER

[0012] Colorectal cancer is common in economically developed countries, particularly in Europe, North America and Australia and is the second leading causes of cancer-related deaths in the Western world. Every year, colorectal cancer is responsible for arr estimated 400,000 deaths worldwide. Approximately 60,000 people die from colorectal adenocarcinoma among the 150,000 new cases, which are diagnosed in Europe each year. A genetic contribution to colon cancer risk is suggested by two observations, namely a) an increased incidence of colorectal cancer among persons with a family history of colorectal cancer and b) families in which multiple family members are affected with colorectal cancer, in a pattern indicating autosomal dominant inheritence of cancer susceptibility (Burt et al 2004, Gastroenterology. 2004;127(2):444-51 ; Vasen et al 1996, Lancet. 17;348(9025):433-5). About 25% of patients with colorectal cancer have a family history of the disease while the remaining 75% of patients have sporadic disease, with no apparent evidence of inheriting the disease.

[0013] NATURAL HISTORY OF COLORECTAL CANCER

[0014] Colorectal tumours present with a broad spectrum of neoplasms, ranging from benign growths to invasive cancer and are predominantly epithelial in origin (i.e adenomas or adenocarcinomas). Pathologists have classified the lesion into three groups: nonneoplastic polyps, neoplastic polyps (adenomatous polyps, adenomas) and cancers.

[0015] Over 95% of colorectal cancers are carcinomas, most of which are adenocarcinomas. A personal/familial history of having colon adenomas places one at increased risk of developing colon cancer (Neale and Ritchie, in Herrera L, ed. Familial Adenomatous Polyposis. New York, NY; Alan R. Liss Inc., 1990 p61-66) suggesting that either the adenoma may reflect an innate or acquired tendency of the colon to form tumour or that adenomas might be the primary precursor lesion of the colon cancer. While there is no direct proof that the majority of colorectal cancers arise from adenomas, adenocarcinomas are generally considered to arise from adenomas because a) benign and malignant tissue occur within colorectal tumours (Perzin and Bridge 1981 , Cancer.48(3):799-819) and b) when patients with adenomas were followed for 20 years, the risk of cancer at the site of the adenoma was 25%, a rate much higher than the expected norm (Stryker et al 1987, Gastroenterology. 1987;93(5): 1009-13). In addition, removal of adenomatious polyps is associated with reduced colorectal cancer incidence (Muller and Sonnenberg 1995, Ann Intern Med. 15;123(12):904-10).

[0016] GENESIS OF COLON CANCER

[0017] The colon is organized into compartments of cells called crypts, where stem cells that reside near the bottom give rise to transit amplyifying cells that undergo five to seven additional divisions before they become terminally differentiated into one of four cell types, namely colonocytes, goblet cells, Paneth cells and enteroendocrine cells ( Brittan

[0018] & Wright 2004, Gut.;53(6):899-910). Three of the four cells types (exception being

[0019] Paneth cells) continue to migrate to the top of the crypt where they undergo apoptosis and are engulfed by stromal cells or are shed into the lumen. For tissue homeostasis to ensue, the birth rate of the colonic epithelial cells precisely equals ther rate of loss from the crypt apex. If birth/ loss ratio increases, a neoplasm occurs.

[0020] Since the differentiated epithelial cells have a fixed residency under normal conditions, it would appear that key to the genesis of colon cancer is that for cells to be able to accumulate mutations and form a polyp and early adenoma in this tissue, they have to become refractory to apoptosis. It is widely believed adenomas develop from normal stem cells through molecular abnormalities (Bach et al 2000, Carcinogenesis. 21(3):469- 76). However, a single random major deleterious molecular alteration is not sufficient to induce carcinogenesis. Indeed, even sustained expression of well known oncogenes, including SV-40 T antigen, human K-ras VaH 2 and a dominant negative mutant of human p53 alone or in combination do not lead to adenomas over a 9-12 month period (Kim et al 1993, J Cell Biol;123(4):877-93). One molecular alteration that seems pivotal to the genesis of colon cancer is the mutation of the APC protein such that approximately 85% of all colon cancers have this protein mutated. In addition, mutation of this gene seems to be one of the earliest events in the colorectal tumour progression pathway ( Kinzler & Vogelstein, 1998 in The Genetic Basis of Human Cancer (McGraw-Hill, Toronto). ). As such, the APC protein is viewed as a gatekeeper of colon cancer.

check out the new patent.. news imminent

GSK LOVES ERX

katcenka
Cheers plenty to read there that relates, that makes a change.

That's only part of the patent you should see the long winded stuff!

laurie
I like a long wind.

yes its talks about GSK, thats what i really like about it

http://www.madison.com/wsj/home/biz/index.php?ntid=122494&ntpid=2

MGI Pharma to Present at the Cowen and Company 27th Annual Healthcare Conference


MINNEAPOLIS--(BUSINESS WIRE)--Mar 8, 2007 - MGI PHARMA, INC. (Nasdaq:MOGN) today announced that Bill Spengler, Executive Vice President and Chief Financial Officer of MGI PHARMA, will present at the Cowen and Company 27th Annual Healthcare Conference in Boston, MA on Thursday, March 15, 2007 at 8:00 a.m. Eastern Time. Mr. Spengler will provide an overview of the Company, its products, pipeline and 2007 corporate goals.

The presentation will be webcast live and may be accessed by logging on to MGI PHARMA's corporate website at www.mgipharma.com. Please connect to the Company's website at least 15 minutes prior to the live presentation to ensure adequate time for any software download that may be necessary to listen to the webcast. An archived version of the presentation will be available through March 22, 2007.

OSI Pharmaceuticals, Inc. at Cowen and Company Annual Health Care Conference
Thursday, March 15, 2007 8:45 a.m. ET

http://www.corkairpark.ie/phase01.htm

EIRX and Pfizer, THEY ARE IN THE SAME BUILDING!!!!, wonder if they are part of the JV

http://www.pfizer.com/pfizer/help/download/index_pipeline.jsp?page=2

Pfizer link.. looks more and more promising, read this and what pfizer has to say

http://www.sddt.com/News/article.cfm?SourceCode=20070327cra

RNS out tomorrow or friday..

Oncology mission for Scottish Life Sciences organisations

Ten of Scotlands leading companies and universities specialising in oncology research and development are participating in a trade mission to Massachusetts to develop closer links with global pharmaceutical companies based in the region.

The trip, which has been co-ordinated by Scottish Development Internationals life sciences team, will enable participants to meet with the US-based companies and identify how the work of Scottish based universities and companies could help advance the work of these companies in developing new treatments for cancer related illnesses.

Massachusetts has one of the largest concentrations of life sciences companies in the world with more than 280 companies and 30,000 employees working in the sector and an internationally renowned academic base. The Scottish delegation will be meeting some of the worlds leading pharmaceutical and biotechnology companies including Pfizer, Amgen and Genzyme to help open up new business opportunities.

The US companies will learn about Scotlands leading oncology centres of excellence, including the recently opened Beatson Institute at the University of Glasgows Garscube Estate and the University of Edinburghs Cancer Research Centre, which has been developed in partnership with Cancer Research UK. Leading Scottish companies such as Cyclacel Pharmaceuticals, CXR Biosciences and EiRx Therapeutics will also be attending to identify potential collaborative opportunities with the US-based firms.

Ian Leslie, team leader of the Scottish Development International Life Sciences team says: Boston and the wider Massachusetts state is regarded as one of the worlds leading life sciences locations and home to some of the worlds biggest pharmaceutical and biotech companies. Scotlands world class reputation in the oncology field has helped us get the foot in the door with these global firms and this trip will be hugely important in promoting Scotlands strengths in oncology research and developing new opportunities for collaborative working and new business opportunities for Scottish based organisations.

Scottish Biomedical, a drug discovery services company based in Glasgow, is one of the companies participating and hopes the trip will lead to developing new relationships overseas.

Simon Bury, Business Development Director of Scottish Biomedical, says: The US is obviously a very lucrative market for life sciences and Massachussets is a key market to target. This trip is enabling us to meet with a number of global companies and hopefully develop new relationships to capitalise on our existing contacts overseas.

Oncology is one of Scotlands leading areas of life sciences research and one which has significant commercial potential. There are almost fifty major research groups, centre of excellence and departments within eight Scottish Universities and Research Institutes, working to understand the causes of different cancers and developing new treatments. There is also a growing base of companies actively looking at drug discovery and development to develop new cancer therapeutics.

The full list of organisations participating in the trade mission are: Accuro Biologics Ltd; CXR Biosciences; Cyclacel Pharmaceuticals; EiRx Therapeutics PLC; Nexus Oncology; Scottish Biomedical; University of Aberdeen; University of Dundee; University of Edinburgh and University of Glasgow.

Media Contact

Neil McInnes, Senior Media Relations Executive
Scottish Enterprise
Tel: 0131 313 6196 / 07881 517712
E-mail: neil.mcinnes@scotent.co.uk

Notes to Editors

Scottish Development International works to attract inward investment and knowledge to Scotland in order to help the economy grow. SDI also works to help Scottish companies do more business overseas and to promote Scotland as a good place to live, work and do business. It is jointly operated by the Scottish Executive and Scottish Enterprise. Its work is guided by the global connections theme of the Scottish Executive's Smart Successful Scotland strategy for economic development in Scotland.
Massachusetts (MA) in the US is one of the leading centres for life sciences and has more than 280 pharmaceutical and biotech companies (as well as a world-renowned academic base) together with 30,000 employees. Oncology is a key focus for the state with approximately 50 leading human therapeutics companies located in and around the Boston/Cambridge area. Many large pharmaceutical companies including Pfizer and AstraZeneca have major oncology research facilities in the area, and leading key biotechnology companies including Genzyme and Biogen Idec also have significant capabilities.
Background details of all participating Scottish organisations:
Accuro Biologics Ltd

Accuro Biologics is a research services company providing a new option to those seeking to outsource their needs in antibody and protein engineering, mammalian cell line development and immunogenicity profiling. Created in 2005 and operating from its own fully equipped facilities in the UK, the company services are delivered by a highly experienced laboratory and management team. The company provides a fully flexible approach to its projects and commercial arrangements and seeks to provide access to its advanced capabilities without prohibitive cost and additional royalty burdens to its clients.


EiRx Therapeutics PLC

EiRx Therapeutics (LSE: ERX) is a research-driven healthcare company developing new targeted therapies for the treatment of cancer. The company operates from laboratories in Cork, Ireland, and Aberdeen, Scotland, and has an initial focus on colorectal and breast tumours. EiRx develops novel, small molecule inhibitors of key cellular signalling pathways that have the potential to treat cancer by specific induction of apoptosis in tumour cells. EiRx also undertakes biomarker discovery and validation work using a large biorepository of surgical tumour specimens. EiRx has licensed drug targets to OSI Pharma and MGI Pharma, and has active biomarker collaborations with bioMieux SA and Almac Diagnostics.

http://www.scottish-enterprise.com/sedotcom_home/news-se/news-fullarticle.htm?articleid=192953


hmm very interesting, seems to go with the above article as well


http://www.corkairpark.ie/phase01.htm

EIRX and Pfizer, THEY ARE IN THE SAME BUILDING!!!!, wonder if they are part of the JV

OSI Pharmaceuticals Inc.

OSI Pharmaceuticals, Inc., a biotechnology company, engages in the discovery, development, and commercialization of oncology products for cancer patients in the United States.

Its flagship product, Tarceva, is an oral, once-a-day, small molecule inhibitor of the epidermal growth factor receptor.

The company also markets Novantrone for the approved oncology indications; and Gelclair for the relief of pain associated with oral mucositis.

Its other drug candidates include OSI-7904L, a liposomal formulation of a potent thymidylate synthase inhibitor, which is in phase II study; OSI-461, an inhibitor of cGMP phosphodiesterases, which is in phase I dose optimization study; and OSI-930, a tyrosine kinase inhibitor, which is in preclinical research stage.

In addition, OSI Pharmaceuticals, through its collaborative drug discovery program, develops CP-547,632, which targets vascular endothelial growth factor receptor and is in Phase II and Phase I trials; CP-868,596 that targets tumor derived angiogenesis and is in Phase I trials; and CP-724,714, which is an oral inhibitor of epidermal growth factor receptor 2 and is in Phase I clinical trial.

Further, its subsidiary, Prosidion Limited, specializes in diabetes and obesity treatment in the United Kingdom.

The company has collaboration agreements with Pfizer, Inc.; Cold Spring Harbor Laboratory; EiRX Therapeutics plc; Genentech, Inc.; and Roche.

OSI Pharmaceuticals is headquartered in Melville, New York.

http://www.lexdon.com/profile/OSI_Pharmaceuticals_Inc./osip.html

so no one left in this then?

katcenka
Yes still accumulating.

im in too
Alex

yawn---zzzzz I'm still here!

are you sure..

yep ! zzz