What is a Pharmacological Chaperone?
Pharmacological Chaperones (PCs) are small molecules that restore the proper folding of misfolded proteins. Back to Index
How are PCs classified?
PCs are broadly categorized into two distinct types: First-generation (Orthosteric) and Second-generation (Allosteric). For clarity and consistency in classification, we have designated compounds with inhibitory effects as First-generation PCs when the binding site is not explicitly identified in the literature. Conversely, drugs that lack inhibitory effects but stabilize their targets, or those targeting non-enzymatic proteins, are classified as Second-generation PCs. Back to Index
What is a Rare Disease?
According to Orphanet, rare diseases (RD) are conditions that affect a small number of individuals compared to the general population (≤ 1 in 2,000 people in Europe). Back to Index
What is a Rare Conformational Disease?
A subset of rare diseases in which the pathogenic phenotype is associated with protein misfolding. Back to Index
What is a Protein Variant?
A modified form of a protein. In our database, we have curated pathogenic and likely pathogenic missense variants from UniProt that are associated with conformational rare diseases (RDs). Back to Index
What is an Efficacy Test?
Any evaluation, ranging from in vitro assays to clinical trials, assessing the susceptibility of a variant to chaperone treatment. Back to Index
What's the possible outcome of an efficacy test?
Given the heterogeneous nature of the efficacy tests, we have opted for a simple classification: amenable - the drug is effective in restoring the healthy phenotype; nonamenable - the drug shows moderate activity but is insufficient to restore the healthy phenotype; noactivity - the drug exhibits no measurable effect. Back to Index
How to use CIRCLE?
CIRCLE can be queried by Target, Chaperone, Disease, and Efficacy Test. When hovering over the "Search by" item in the navigation bar at the top-left corner of the platform, a dropdown submenu appears with clickable buttons (Target, Chaperone, Disease, Efficacy Test). Each button directs the user to the corresponding section, where searches can be performed. More detailed instructions are provided within each section. Back to Index