ManRos Therapeutics has chosen a selective panel of key disease-relevant kinases targets.

Kinase inhibitors are “targeted therapies”: they block the growth of cancer cells by interfering with specific targeted molecules, rather than by simply broadly suppressing cell division, as older “non specific” chemotherapeutics do. Targeted therapies are now the fastest growing segment in various therapeutics areas, including oncology. However, despite the wealth of potential targets, marketed drugs or most advanced compounds in clinical development target only a handful of the best-characterized kinases, mainly tyrosine kinases. Among the 518 protein kinases identified, ManRos Therapeutics is concentrating its efforts on a few targets of high therapeutic relevance.

Image: 3D representation of CDK5/p25 co-crystallized with a specific inhibitor targetting the ATP binding pocket of the kinase. Courtesy of Claudia Crovace, Aldo Tarricone and Andrea Musacchio.

Cyclin-dependant Kinases (CDKs)

CDKs are regulatory proteins of the eukaryotic cell proliferation. They act, after association with different cyclins, throughout the progression of the cell division cycle, as central mediators of cell division. Abnormalities in CDK activity and regulation are associated with most cancers. One of the CDKs, CDK5, is a key regulator of neuronal cells. Abnormal regulation of CDK5 is observed in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, as well as ischemia or traumatic brain injury.

Glycogen Synthase Kinases (GSK-3s)

GSK-3’s are essential intracellular signaling regulators involved in numerous physiological processes: pharmacological inhibitors of GSK-3 seem to be useful in the treatment of Alzheimer’s and other neurodegenerative diseases, depression, bipolar affective disorder and diabetes.

Casein Kinases 1 (CK1s)

CK1’s gathers seven serine/threonine enzymes that act as regulators of signal transduction pathways in most eukaryotic cells. They are clearly specifically involved in cancers as well as in the development of Alzheimer’s disease.

ManRos Therapeutics is also pursuing research on new selective inhibitors targeting other, poorly investigated families of kinases that are implicated in specific diseases.