Core Components of a Small Molecule Target Service A comprehensive service follows the early drug discovery workflow: 1. Target Identification & Prioritization Bioinformatics & Omics Analysis: Mining genomic, proteomic, and clinical data to find proteins or pathways dysregulated in a disease. Genetic Screens: Using CRISPR-Cas9 or RNAi to knock out/knock down genes and identify which are essential for disease cell survival. Literature & Database Mining: Systematic review of existing scientific and patent data to propose novel or repurposable targets. 2. Target Validation In Vitro Models: Confirming the target's role in disease using engineered cell lines (overexpression, knockout) and relevant disease models (e.g., cancer cell lines, neuronal cultures). In Vivo Models: Using animal models (e.g., zebrafish, mice) to see if modulating the target (genetically or with a tool compound) has the desired therapeutic effect and is safe. Biochemical Validation: Demonstrating the target protein is expressed, has the expected activity, and is "druggable" (has a pocket where a small molecule can bind). 3. Assay Development & Screening This is a critical service. Providers develop robust tests ("assays") to measure target activity. Types of Assays: Biochemical Assays: Test compound binding/interaction with the purified target protein (e.g., enzymatic activity, protein-protein interaction). Cell-Based Assays: Test compound function in a living cell (e.g., reporter…
Core Concept The central idea is "Target-based Drug Discovery." Instead of screening compounds on whole cells or organisms (phenotypic screening), you start with a specific protein (e.g., a kinase, receptor, ion channel) implicated in a disease. Services then help you understand that target and find molecules that modulate it. Categories of Protein Target Services These services typically follow the drug discovery pipeline: 1. Target Identification & Validation Bioinformatics & Omics Analysis: Mining genomic, proteomic, and clinical data to identify novel disease-associated targets. Genetic Validation: CRISPR/Cas9 gene editing (knock-out/knock-in), siRNA/shRNA knockdown to confirm the target's role in disease pathways. Functional Validation: Cell-based assays to see if modulating the target affects disease-relevant phenotypes. 2. Protein Expression & Purification Recombinant Protein Production: Cloning, expressing (in E. coli, insect, or mammalian cells), and purifying milligram to gram quantities of the target protein. This is essential for structural studies and biochemical assays. Membrane Protein Expertise: Specialized services for difficult-to-express targets like GPCRs and ion channels. Tagging & Labeling: Adding tags (His, GST, FLAG) for purification or fluorescent/isotopic labels for assays. 3. Structural Biology & Biophysics X-ray Crystallography: Determining high-resolution 3D structures of protein-ligand complexes. Cryo-Electron Microscopy (Cryo-EM): For large complexes or membrane proteins unsuitable for crystallography. Nuclear Magnetic Resonance (NMR) Spectroscopy: For studying dynamics and ligand binding in solution. Surface…
