Science Selects Cyclacel Work As Editor's Choice

Dundee, UK - 8 November 2004 - Cyclacel Group plc (“Cyclacel”), the UK-based biopharmaceutical company, announced today that the Editor of Science magazine cited a chemistry paper by Cyclacel scientists regarding its CYC103 targeted drug discovery program. In its review of selected highlights in the recent literature, the Editor’s Choice section of the 1 October 2004 issue of Science summarized a publication in which a Cyclacel team reported on its development of novel cell cycle inhibitors of the CDK2/cyclin A drug target.

Tumor suppressor genes, the body’s own anticancer drugs, induce cancer cell death by inhibiting both CDK enzyme and cyclin protein targets. Several investigational anticancer drugs, such as Cyclacel’s seliciclib (CYC202), target these CDK mechanisms. Drug designers typically prefer enzymes over proteins as the latter are viewed as very difficult targets. Uniquely Cyclacel is targeting both CDK enzymes in its CYC200 and CYC400 programs and cyclin A proteins in its CYC103 program.

Cyclacel’s crystallographers solved the structures of a series of inhibitors bound to a specific part of the cyclin A target that was discovered and patented by Cyclacel. This breakthrough was previously presented at a Keystone, Colorado, symposium,Protein Kinases and Cancer: The Promise of Molecular-Based Therapies, and published in the journal Structure earlier this year. This suggested that the target cyclin A inhibitor site was small enough to accommodate a small molecule drug. By incorporating structural constraints into a flexible molecule Cyclacel medicinal chemists produced a rigid molecule. This new molecule showed considerable increase in potency against the target.

Cyclacel’s CYC103 program aims to develop inhibitors of CDK/cyclins acting at the binding site on the cyclin. This is a complementary approach to targeting the CDK site. Cyclacel’s CYC103 program builds on early work by the company’s scientific founder, Professor Sir David Lane, who identified the region of p21WAF1 which acts as a natural inhibitor of the cyclin binding groove motif (CBG) at the cyclin binding site.

Bob Jackson PhD, Cyclacel’s Chief Scientific Officer, said: “It is gratifying to see the innovative work of our scientists recognized by a prestigious journal. Our talented scientists have discovered potent molecules interacting with the cyclin binding groove despite the conventional wisdom favoring ATP-competitive targets.”

About Cyclacel ( www.cyclacel.com )
Cyclacel is a biopharmaceutical company dedicated to the discovery, development and commercialization of novel, mechanism-targeted drugs to treat human cancers and other serious disorders. The company is currently evaluating seliciclib (CYC202), an orally available cyclin dependent kinase inhibitor, in Phase II clinical trials for the treatment of non-small cell lung cancer and B-cell hematological malignancies. CYC682 is an orally available, cell cycle modulating nucleoside analog in Phase I clinical trials for the treatment of cancer. Cyclacel also has seven programs in preclinical development.

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