10th Apr 2008 07:01
Sareum Holdings PLC10 April 2008 For immediate release 10 April 2008 SAREUM HOLDINGS PLC ("Sareum" or the "Company") Sareum to Present Chk1 Cancer Research Programme at AACR Annual Meeting 2008 Sareum Holdings plc (Sareum) (AIM: SAR), the specialist structure-based drugdiscovery business, is pleased to announce that it will present the latestresults from its joint research collaboration with The Institute of CancerResearch and Cancer Research Technology Ltd. at the American Association forCancer Research (AACR) annual meeting, to be held on April 12-16 2008 in SanDiego, CA. Dr John Reader, VP of Chemistry at Sareum, will present a poster entitled "Identification and structure-guided optimization of novel inhibitors ofCheckpoint kinase 1 (Chk1) through combined biochemical and crystallographicscreening" on Sunday April 13. Chk1, the target of the joint research collaboration, is a key component of abiochemical pathway responsible for preventing the effectiveness of traditionalcancer therapeutics such as chemotherapy. The aim of the collaboration, firstannounced in July 2005, is to develop novel cancer treatments with the potentialto have efficacy against tumours that do not respond to chemotherapy and/orfewer adverse side-effects as a result of lower doses of chemotherapy beingrequired. In August 2006 the collaboration announced the discovery of a novelcompound series which showed activity in cancer cell models, and in February2007 it was announced that a series of patent applications had been filed tosecure the intellectual property rights related to compounds developed in thecollaboration. Sareum has used its expertise in fragment and structure-based drug discovery toidentify novel chemical compounds effective against Chk1. These compound serieshave been rapidly progressed towards drug candidates utilising Sareum's highthroughput medicinal chemistry and structure determination platforms combinedwith the drug screening, specialist cancer biology and medicinal chemistryexpertise at The Cancer Research UK Centre for Cancer Therapeutics at TheInstitute. Commenting on the announcement, Sareum's Chief Executive Officer, Dr TimMitchell, said: "We have made excellent progress in this highly successfulcancer research collaboration and we are delighted to be making our first publicpresentations of these advances. These collaborations endorse Sareum'stechnology and the experience of our team." For more information, please contact: Sareum Holdings plc 01223 497700 Tim Mitchell, Chief Executive Officer Buchanan Communications 020 7466 5000 Mary-Jane Johnson, Tim Anderson Grant Thornton Corporate Finance 020 7383 5100 Philip Secrett, Colin Aaronson Notes for editors: About Checkpoint Kinase 1 Many known cancer treatments cause DNA damage by either physically modifying thecell's DNA or disrupting vital cellular processes that can affect the fidelityof DNA replication and cell division, such as DNA metabolism, DNA synthesis, DNAtranscription and microtubule spindle formation. Such treatments include forexample, radiotherapy, which causes DNA strand breaks, and a variety ofchemotherapeutic agents including topoisomerase inhibitors, antimetabolites,DNA-alkylating agents, and platinum-containing cytotoxic drugs. A significantlimitation to these genotoxic treatments is drug resistance. One of the mostimportant mechanisms leading to this resistance is attributed to activation ofcell cycle checkpoints, giving the tumour cell time to repair damaged DNA. Byabrogating a particular cell cycle checkpoint, or inhibiting a particular formof DNA repair, it may therefore be possible to circumvent tumour cell resistanceto the genotoxic agents and augment tumour cell death induced by DNA damage,thus increasing the therapeutic index of these cancer treatments. Checkpoint Kinase 1 (Chk1) is a serine/threonine kinase involved in regulatingcell cycle checkpoint signals that are activated in response to DNA damage anderrors in DNA caused by defective replication. Chk1 transduces these signalsthrough phosphorylation of substrates involved in a number of cellularactivities including cell cycle arrest and DNA repair. Two key substrates ofChk1 are the Cdc25A and Cdc25C phosphatases that dephosphorylate CDK1 leading toits activation, which is a requirement for exit from G2 into mitosis (M phase).Phosphorylation of Cdc25C and the related Cdc25A by Chk1 blocks their ability toactivate CDK1, thus preventing the cell from exiting G2 into M phase. The roleof Chk1 in the DNA damage-induced G2 cell cycle checkpoint has been demonstratedin a number of studies where Chk1 function has been knocked out. The reliance of the DNA damage-induced G2 checkpoint upon Chk1 provides oneexample of a therapeutic strategy for cancer treatment, involving targetedinhibition of Chk1. Upon DNA damage, the p53 tumour suppressor protein isstabilised and activated to give a p53-dependent G1 arrest, leading to apoptosisor DNA repair. Over half of all cancers are functionally defective for p53,which can make them resistant to genotoxic cancer treatments such as ionisingradiation and certain forms of chemotherapy. These p53 deficient cells fail toarrest at the G1 checkpoint or undergo apoptosis or DNA repair, and consequentlymay be more reliant on the G2 checkpoint for viability and replication fidelity. Abrogation of the G2 checkpoint through inhibition of the Chk1 kinase functionhas been demonstrated to selectively sensitise p53 deficient cancer cells togenotoxic cancer therapies. About Sareum Holdings plc Sareum Holdings plc is a structure-based drug discovery business headquarteredin Cambridge, UK. The Company was formed in August 2003 to discover new drugsfor the treatment of cancer. Sareum's unique approach aims to halve the time ittakes to discover new drug candidates. A structure-based approach to drug discovery relies on knowledge of thethree-dimensional structure of the proteins that cause disease. Once thestructure is known, potential drugs are designed to 'lock-in' to the proteinwith the aim of reversing or arresting a disease's progression. Knowledge ofthe structure of the potential drugs and how they 'lock-in' to their targetprotein assists greatly in the development of high-quality drug candidates.Determining structure is a complex task and requires leading-edge equipment andexperienced staff. Sareum's approach to structure determination utilises itsproprietary protein expression platform in order to produce multiple recombinantproteins that accelerate structure determination using x-ray crystallography. Once the structure is determined, the Company's innovative fragment screeningplatform is used to identify novel chemical templates designed to interact withthe target protein. Sareum then uses its high-throughput medicinal chemistryplatform to rapidly optimise these molecules and develop the most promising intopotential drug candidates. Sareum aims to successfully deliver drug candidates for licensing to largerpharmaceutical companies at the pre-clinical or early clinical trials stage.This is funded by provision of its specialist drug discovery capabilities topartners in the pharmaceutical and biotechnology industries. Sareum joined the AIM market of the London Stock Exchange in October 2004 andtrades under the symbol SAR. For further information, please visitwww.sareum.co.uk This information is provided by RNS The company news service from the London Stock ExchangeRelated Shares:
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