Presentation at AACR
Sareum Holdings PLC
10 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 drug
discovery business, is pleased to announce that it will present the latest
results from its joint research collaboration with The Institute of Cancer
Research and Cancer Research Technology Ltd. at the American Association for
Cancer Research (AACR) annual meeting, to be held on April 12-16 2008 in San
Diego, CA.
Dr John Reader, VP of Chemistry at Sareum, will present a poster entitled
"Identification and structure-guided optimization of novel inhibitors of
Checkpoint kinase 1 (Chk1) through combined biochemical and crystallographic
screening" on Sunday April 13.
Chk1, the target of the joint research collaboration, is a key component of a
biochemical pathway responsible for preventing the effectiveness of traditional
cancer therapeutics such as chemotherapy. The aim of the collaboration, first
announced in July 2005, is to develop novel cancer treatments with the potential
to have efficacy against tumours that do not respond to chemotherapy and/or
fewer adverse side-effects as a result of lower doses of chemotherapy being
required. In August 2006 the collaboration announced the discovery of a novel
compound series which showed activity in cancer cell models, and in February
2007 it was announced that a series of patent applications had been filed to
secure the intellectual property rights related to compounds developed in the
collaboration.
Sareum has used its expertise in fragment and structure-based drug discovery to
identify novel chemical compounds effective against Chk1. These compound series
have been rapidly progressed towards drug candidates utilising Sareum's high
throughput medicinal chemistry and structure determination platforms combined
with the drug screening, specialist cancer biology and medicinal chemistry
expertise at The Cancer Research UK Centre for Cancer Therapeutics at The
Institute.
Commenting on the announcement, Sareum's Chief Executive Officer, Dr Tim
Mitchell, said: "We have made excellent progress in this highly successful
cancer research collaboration and we are delighted to be making our first public
presentations of these advances. These collaborations endorse Sareum's
technology 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 the
cell's DNA or disrupting vital cellular processes that can affect the fidelity
of DNA replication and cell division, such as DNA metabolism, DNA synthesis, DNA
transcription and microtubule spindle formation. Such treatments include for
example, radiotherapy, which causes DNA strand breaks, and a variety of
chemotherapeutic agents including topoisomerase inhibitors, antimetabolites,
DNA-alkylating agents, and platinum-containing cytotoxic drugs. A significant
limitation to these genotoxic treatments is drug resistance. One of the most
important mechanisms leading to this resistance is attributed to activation of
cell cycle checkpoints, giving the tumour cell time to repair damaged DNA. By
abrogating a particular cell cycle checkpoint, or inhibiting a particular form
of DNA repair, it may therefore be possible to circumvent tumour cell resistance
to 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 regulating
cell cycle checkpoint signals that are activated in response to DNA damage and
errors in DNA caused by defective replication. Chk1 transduces these signals
through phosphorylation of substrates involved in a number of cellular
activities including cell cycle arrest and DNA repair. Two key substrates of
Chk1 are the Cdc25A and Cdc25C phosphatases that dephosphorylate CDK1 leading to
its 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 to
activate CDK1, thus preventing the cell from exiting G2 into M phase. The role
of Chk1 in the DNA damage-induced G2 cell cycle checkpoint has been demonstrated
in a number of studies where Chk1 function has been knocked out.
The reliance of the DNA damage-induced G2 checkpoint upon Chk1 provides one
example of a therapeutic strategy for cancer treatment, involving targeted
inhibition of Chk1. Upon DNA damage, the p53 tumour suppressor protein is
stabilised and activated to give a p53-dependent G1 arrest, leading to apoptosis
or DNA repair. Over half of all cancers are functionally defective for p53,
which can make them resistant to genotoxic cancer treatments such as ionising
radiation and certain forms of chemotherapy. These p53 deficient cells fail to
arrest at the G1 checkpoint or undergo apoptosis or DNA repair, and consequently
may be more reliant on the G2 checkpoint for viability and replication fidelity.
Abrogation of the G2 checkpoint through inhibition of the Chk1 kinase function
has been demonstrated to selectively sensitise p53 deficient cancer cells to
genotoxic cancer therapies.
About Sareum Holdings plc
Sareum Holdings plc is a structure-based drug discovery business headquartered
in Cambridge, UK. The Company was formed in August 2003 to discover new drugs
for the treatment of cancer. Sareum's unique approach aims to halve the time it
takes to discover new drug candidates.
A structure-based approach to drug discovery relies on knowledge of the
three-dimensional structure of the proteins that cause disease. Once the
structure is known, potential drugs are designed to 'lock-in' to the protein
with the aim of reversing or arresting a disease's progression. Knowledge of
the structure of the potential drugs and how they 'lock-in' to their target
protein assists greatly in the development of high-quality drug candidates.
Determining structure is a complex task and requires leading-edge equipment and
experienced staff. Sareum's approach to structure determination utilises its
proprietary protein expression platform in order to produce multiple recombinant
proteins that accelerate structure determination using x-ray crystallography.
Once the structure is determined, the Company's innovative fragment screening
platform is used to identify novel chemical templates designed to interact with
the target protein. Sareum then uses its high-throughput medicinal chemistry
platform to rapidly optimise these molecules and develop the most promising into
potential drug candidates.
Sareum aims to successfully deliver drug candidates for licensing to larger
pharmaceutical companies at the pre-clinical or early clinical trials stage.
This is funded by provision of its specialist drug discovery capabilities to
partners in the pharmaceutical and biotechnology industries.
Sareum joined the AIM market of the London Stock Exchange in October 2004 and
trades under the symbol SAR. For further information, please visit
www.sareum.co.uk
This information is provided by RNS
The company news service from the London Stock Exchange E