Off-the-Shelf Kinase Structures
The term "off-the-shelf" structures is used for cases when the company has produced the protein in question, successfully crystallized it, collected X-ray data and determined the structure. In addition, a protein is kept in the freezer for quick crystallization, when required. In such cases the clients ligands may be quickly co-crystallized with these proteins and the structure of the complex will be returned within 3-4 weeks.
CK2 kinase is a pleiotropic serine/threonine protein kinase that plays a global role in activities related to cell growth, cell death, and cell survival (1). Elevated CK2 activity has been associated with malignant transformation and aggressive tumor growth and it has thus emerged as an attractive molecular target for drug design (1). The interest in developing small molecule inhibitors of CK2 has recently increased due to (2):
• The identification of ATP-binding site specific chemotypes
• The potential for targeting allosteric sites
• The potential for developing compounds that interfere with heterodimer formation
Recently, a selective CK2alpha inhibitor with oral bioavailability designated CX-4945 by Cylene Pharmaceuticals, entered Phase I clinical trials for advanced solid tumors and multiple myeloma (clinicaltrials.gov identifier: NCT00891280). The results have recently been published and show that targeting CK2 in humans is a viable strategy for treating many cancers. Read more...
1. Trembley JH, Wang G, Unger G, Slaton J, Ahmed K., 2009. Protein kinase CK2 in health and disease: CK2: a key player in cancer biology. Cell Mol Life Sci. 66, 1858-67.
2. Ermakova I, Boldyreff B, Issinger OG, Niefind K., 2003. Crystal structure of a C-terminal deletion mutant of human protein kinase CK2 catalytic subunit. J Mol Biol. 330, 925-34.
PIM1 protein kinase belongs to a family of serine/threonine protein kinases that is involved in the control of cell growth, differentiation and apoptosis. As an oncogene PIM1 has been implicated in multiple human cancers, including prostate cancer, acute myeloid leukemia and other hematopoietic malignancies.
We currently offer co-crystal structures of fragments co-crystallized with CK2 and PIM1. The fragments have verified inhibitory activity against these kinases. If you are interest in new CK2 or PIM1 inhibitors, please do not hesitate to contact us.