The 2P2IDB contains a total of 17 protein/protein complexes corresponding to 14 families and 56 small molecule inhibitors bound to the corresponding target. There are a limited number of targets in the 2P2I database at this stage due to the structural prerequisites that were used. However, it is inevitable that high throughput structural genomic programs will generate a high level of data. In addition, the development of improved methodologies for the development of small molecule inhibitors will rapidly lead to the discovery and structural characterization of disruptors of new PPI families. These new targets and their corresponding ligands will be incorporated into the database as they appear in the literature and the Protein Data Bank. To assess the characteristics of druggable PPIs, the general properties of the interfaces found in 2P2IDB were compared to those of representative datasets of heterodimeric complexes retrieved from BIBW2992 Bahadur and Zacharias and from the ProtorP server. Trauma to the CNS can BYL719 result in major disruptions in white matter tracts, including breakdown of myelin sheaths. Products of this myelin breakdown come in contact with the surfaces of severed axons and inhibit regeneration. The three known major myelin-derived inhibitors are Nogo-A, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein. All three bind with high affinity to the Nogo-66 receptor on axonal surfaces. Enzymatic cleavage of NgR confirms this effect, in that it increases axon regeneration. It was recently shown that phosphorylation of NgR by casein kinase II also inhibits binding of the myelin-associated proteins and promotes regeneration. Because NgR is a GPI-linked receptor and lacks an intracellular signaling domain, it relies on the transmembrane co-receptor, p75, to transduce the inhibitory signal. The final step in the signaling pathway is the activation of RhoA, a small GTPase that regulates actin polymerization and inhibits axonal elongation in its active form. Nogo-A, MAG, and OMgp activate RhoA through the NgR/p75 receptor complex, and this NgR/p75-complex/RhoA pathway is postulated to be responsible for the inhibitory signals that prevent axon regeneration. Recent pharmacological methods to overcome CNS myelin inhibition involved the use of an anti-Nogo antibody, RhoA inhibitors, a NgR antagonist peptide, and soluble NgR. There are potential problems with these inhibitors as therapeutic agents. For example, the direct blockade of RhoA with an inhibitor may disrupt other, crucial Rho-related cellular activities. In contrast, the anti-Nogo antibodies are only specific for Nogo and do not disrupt MAG or OMgp action. Because of this, it may be useful to identify high affinity inhibitors that more generally interact with the surface of NgR. Aptamers are single-stranded oligonucleotides that fold into unique three-dimensional structures, allowing them to bind to protein targets with high affinity and specificity. They are an alternative to therapeutic antibodies but can be chemically synthesized in a cell-free system. Furthermore, aptamers have a number of advantages over peptide and protein antagonists, including their relatively low cost of production, ease of GMP manufacture, and the simplicity with which they can be modified for stability, signaling, and immobilization. Studies have shown that aptamers have no or low immunogenicity, and are generally non-toxic, which is a great advantage in comparison to antibodies given the length of treatment period required for spinal cord injuries.