Novel Mitotic Kinase Inhibitors

Summary

The present Competitive Intelligence Report about Novel Mitotic Kinase Inhibitors provides a competitor evaluation in the field of synthetic molecules targeting polo-like kinase 1 (Plk-1), cyclin-dependent kinase (CDK) or aurora kinase for treatment of cancer as of June 2009.

Mitosis, a central event in tumor growth, is highly regulated to ensure accurate and equal segregation of genetic materials from parent cells to daughter cells. Main effectors of this process are mitotic spindles and centrosomes.157 Disruption of the process results in aneuploidy, and genomic instability renders the cellular condition optimal for apoptosis to occur. The rationale of targeting mitosis in cancer therapy is substantiated by the successful clinical development of tubulin-disrupting agents, such as vinca alkaloids and taxanes.

The coordination of progression through mitosis is mainly orchestrated by protein phosphorylation insured by several serine/threonine kinases of which the three main mitotic kinase families are the cyclin-dependent kinase CDKs), the polo-like kinases (Plks), and the Aurora kinases.

The Polo-Like Kinases form a family of four different proteins that regulates many aspects of the cell cycle progression. They all share small conserved domains named polo-box required fort protein localization. Only Plk1 that is the most extensively studied, is a true mitotic. Plk2, Plk3 and Plk4 are more likely involved only in interphase.

Cyclin Dependant Kinases that must associate to a cyclin to become active kinases are key regulators of cell cycle progression. There are now about twelve Cdks. Some CDKs, such as CDK1-CDK4, CDK6 and perhaps CDK11, are involved in progression through the cell cycle, whereas CDK7 has dual roles as a CDK-activating kinase (CAK) and a regulator of the transcriptional machinery. CDK8 and CDK9 seem to have key roles in the control of transcription by RNA polymerase II.

Mammals have three Aurora kinases, named Aurora A, B and C. Aurora A has distinct functions while Aurora B and C share same functions, though all three kinases are involved in the control of many processes required for mitosis.

The report includes a compilation of current active projects in research and development of synthetic molecules targeting polo-like kinase 1 (Plk-1), cyclin-dependent kinase (CDK) or aurora kinase. In addition, the report lists company-specific R&D pipelines of novel mitotic kinase targeting molecules. Competitor projects are listed in a tabular format providing information on:

• Drug Codes,
• Target / Mechanism of Action,
• Class of Compound,
• Company,
• Product Category,
• Indication,
• R&D Stage and
• additional comments with a hyperlink leading to the source of information.

Contents

• Index
  • Polo-like Kinase 1 (Plk-1) Inhibitors
  • Cyclin-dependent Kinase (CDK) Inhibitors
  • Aurora Kinase Inhibitors
  • Corporate Novel Mitotic Kinase Inhibitor R&D Pipelines
  • About La Merie
• Companies mentioned in the Competitor Analysis
  • Ambit Biosciences
  • Astex Therapeutics
  • AstraZeneca
  • Aurigene Discovery Technologies
  • Boehringer Ingelheim
  • Cetek
  • Chroma Therapeutics
  • Clinical Data (acquired Avalon Pharmaceuticals)
  • CompleGen
  • Crystal Genomics
  • Cyclacel
  • Elara Pharmaceuticals
  • EntreMed
  • Exelixis
  • GlaxoSmithKline
  • GPC Biotech
  • Keryx Pharmaceuticals
  • Kyowa Hakko Kirin Pharma
  • ManRos
  • Merck & Co
  • Merck Serono
  • Nervano Medical Sciences
  • Nicholas Piramal
  • Novartis
  • Onconova Therapeutics
  • Pfizer
  • ProBioDrug
  • Rigel Pharmaceuticals
  • Sanofi-Aventis
  • Sareum
  • S*Bio
  • Schering-Plough
  • Sunesis Pharmaceuticals
  • SuperGen
  • Takeda Pharmaceutical Co
  • Tekmira
  • Telik
  • Tragara Pharmaceuticals
  • TransTech Pharma
  • Vernalis
  • Vertex Pharmaceuticals
  • Vitae Pharmaceuticals