CYC140

Mitosis Regulation

woman in lab

Polo-like kinase 1 (PLK1) is a serine/threonine kinase with a central role in cell division and an important regulator of the DNA damage checkpoint. PLK1 overexpression correlates with poor patient prognosis in several tumors, including esophageal, gastric, leukemia, non–small cell lung cancer, ovarian, and squamous cell cancers, as well as MYC-amplified cancers.

CYC140 is a novel, small molecule, selective and potent PLK1 inhibitor. It has demonstrated impressive efficacy in human tumor xenografts at nontoxic doses. Cyclacel’s translational biology program supports the development of CYC140 in leukemias and solid tumors. CYC140 was designed with improved pharmaceutical properties over earlier clinical-stage PLK inhibitors. Recent data suggest that PLK1 inhibition may be effective in KRAS-mutated metastatic colorectal cancer.
CYC140 - Mitosis illustration

PLK1 is an oncogene playing a key role in regulation of mitotic entry and exit, spindle formation and cytokinesis, or cell separation into daughter cells. Cancer cells are very sensitive to PLK1 depletion. This is especially the case with KRAS mutated and p53(—) cells. Normal cells with intact cell cycle checkpoints are less sensitive to PLK1 depletion. In cancer cells, PLK1 inhibition blocks proliferation by prolonged mitotic arrest and induces onset of apoptotic death.

Clinical Trials

Phase 1/2 in Solid Tumors:

Cyclacel is currently planning a streamlined study with oral CYC140 in a broad range of solid tumors in multiple cohorts defined by cancer histology. The study aims to determine recommended phase 2 dosing schedules and identify clinical activity that may lead to registration-enabling outcomes.

Phase 1/2 in Leukemias:

A similar streamlined study in a range of leukemias is in planning.

Clinical trial is registered with ClinicalTrials.gov. Learn more about CYC140 trial(s).

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Paul McBarron

Executive Vice President, Chief Financial Officer & Chief Operating Officer​

Mr. McBarron has served as a director of the Company since March 2006. Mr. McBarron joined Cyclacel in January 2002 and has over 30 years of experience with pharmaceutical and biotechnology companies. He has served as a financial executive at Sterling Drug, Sanofi-Winthrop and SmithKline Beecham and, from 1996 to 2001, as a senior member of the finance team at Shire Pharmaceuticals plc, where he held the positions of Director of Corporate Finance and Group Financial Controller. He joined Shire when it was an emerging public company. He qualified as a chartered accountant with Ernst & Young and served on the Scottish Lifesciences Association Board.