CYN 101 Cellular Target—LAMR
Background on the LAMR
The high-affinity laminin receptor (LAMR) is a nonintegrin cell-surface protein that has been identified as the receptor for, among others, the extracellular matrix molecule lamin-1, pathogenic prion protein, Sindbis virus, cytotoxic necrotizing factor type I and II, and adeno-associated virus serotypes 2, 3, 8 and 9. LAMR binds to laminin with high affinity, mediating interactions between laminin and the extracellular environment that affect cell adhesion, tumor growth and metastasis.
LAMR expression levels may act as a prognostic factor in determining the degree of malignancy of human tumors. Over-expression of LAMR may correlate with a highly invasive cell phenotype and increased metastatic ability, mediated by the high affinity binding between LAMR and laminin in the extracellular matrix. The dual function of human LAMR as a receptor at the cell surface and as a component of the translational machinery may be important for understanding how over-expression of LAMR in cancer affects disease pathogenesis.
Structural characterization of the LAMR permits greater understanding of how the LAMR interacts with its binding partners. This in turn may facilitate development of therapeutics that may block and/or mimic LAMR interactions in the setting of, among others, cancer, Alzheimer's disease, other neurological disorders, and viral and bacterial infections. In addition, structural analysis of the LAMR may provide insight into the development of biological and small-molecule therapeutics that aid in the prevention of various disease states, including tumor growth and metastasis.
In addition to the research in cancer therapy targeting LAMR, preliminary data exclusively obtained by the Company confirms published reports that LAMR is implicated in the onset of Alzheimer's disease. The Company has also determined at least one crystal structure of the LAMR and identified several active binding sites wherein compounds may bind to LAMR.
With respect to Alzheimer's disease, LAMR has been shown to interact with the amyloid beta 1-40 peptide, thus blocking fibril formation and even inducing depolymerization of pre-formed fibrils. Thus, the Company's identification of a crystal structure of the LAMR will contribute to an understanding of how LAMR specifically interacts with its binding partners (e.g. amyloid beta 1-40 peptide) and aid in the development of therapeutics that can block and/or mimic LAMR interactions in the setting of, among others, Alzheimer's disease.
In addition, identification of the LAMR crystal structure allows the Company to use existing computer programs to screen the binding interactions between the LAMR crystal structure and thousands, if not millions, of drugs and compounds. The ability to determine LAMR's specific binding interactions with various drugs and compounds will afford the Company an opportunity to rapidly screen the efficacy of such drugs and compounds with respect to, among others, Alzheimer's disease. Accordingly, the Company may soon be instrumental in developing novel therapeutics that may block and/or mimic laminin receptor interactions in the setting of Alzheimer's disease, other neurological disorders, cancers, and viral and bacterial infections.
