December 31, 2009 (FinancialWire) — Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC) (NASDAQ: CYCCP) announced the publication of an article that reviews and discusses the company’s seliciclib (CYC202 or R-roscovitine) product candidate, an orally available inhibitor of multiple cyclin-dependent kinases and its mechanism of action.

The peer-reviewed article, “Cyclin-Dependent Kinase Inhibitors as Anticancer Drugs” was published in the online edition of Current Drug Targets.

“The publication sets out the body of evidence that seliciclib is a promising anti-cancer agent that promotes cancer cell death by down-regulation of key proteins, such as p53 and Mcl-1, associated with survival of cancer cells,” said Professor David Glover, Ph.D., Cyclacel’s Chief Scientist. “A broader therapeutic role for CDK inhibitors in chronic proliferative diseases in addition to cancer has continued to emerge. Recently published evidence suggests that seliciclib promotes apoptosis of uncontrolled white blood cells, including neutrophils and eosinophils, also by down-regulation of Mcl-1. This is a novel finding with promising implications for the treatment of autoimmune and inflammatory conditions, including asthma. It builds upon previously published data showing seliciclib activity in lupus nephritis, polycystic kidney disease, pulmonary fibrosis and rheumatoid arthritis. We look forward to highlighting these non-oncology indications, unveiling Cyclacel’s next-generation CDK inhibitors, and reviewing our promising pipeline programs at a company-sponsored analyst day in 2010.”

Poor therapeutic outcomes and serious side effects are common problems of current cancer therapies. Acquired drug resistance is a further major emerging problem as cancer cells learn to evade the activity of anti-cancer drugs by expressing proteins, such as Mcl-1, that make them immortal. The urgent need for new cancer-targeted drugs that can overcome resistance has led to the development of molecules that specifically inhibit CDKs.

The Current Drug Targets article reports the development of CDK inhibitors and their anti-cancer activities, with special attention to the mechanism of action of multi-kinase CDK inhibitors, including Cyclacel’s seliciclib, currently in Phase 2 clinical trials as a treatment for various cancers. The ability of CDK inhibitors to suppress transcription and sensitize certain cancer cells to apoptosis by down-regulating the expression of the Mcl-1 protein and their synergy in combination with common DNA damaging anti-cancer drugs are also discussed. Citation: Krystof V, Uldrijan S., Cyclin-Dependent Kinase Inhibitors as Anticancer Drugs, Curr Drug Targets. 2009 Dec 23. [Epub ahead of print].

Recently scientists from the Centre for Inflammation Research at the University of Edinburgh published preclinical evidence that seliciclib may be a promising treatment for asthma. They studied the effects of the drug on immune cells of the respiratory system known as eosinophils which help the body fight off infections. Uncontrolled proliferation of eosinophils can damage other cells that line lung tissues and thus contribute to inflammatory conditions such as asthma. Researchers found that exposure to seliciclib caused proliferating eosinophil cells to undergo apoptosis or programmed cell death by down-regulating the expression of the Mcl-1 protein. Citation: Duffin R, et al., The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1, FEBS Lett. 2009 Aug 6;583(15): 2540-6.

Seliciclib is an orally available molecule that selectively inhibits multiple CDK enzyme targets, CDK2/E, CDK2/A, CDK7 and CDK9, that are central to the process of cell division and cell cycle control. Seliciclib has been administered to approximately 450 patients in Phase 1 and Phase 2 trials. It is currently being evaluated in the APPRAISE trial, a Phase 2b randomized double-blinded study as a treatment in patients with non-small cell lung cancer (NSCLC) who failed at least two prior therapies and in a randomized Phase 2 study as a single agent in patients with nasopharyngeal cancer.

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.

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