Final Lecture For Exam 1 PDF

CETSA Cellular Thermal Shift Assay You need to have an idea of what your target is… Molecules 2021, 26, 6083. https://doi.org/10.3390/molecules26196083  Protein Thermal Stability Use a dye, typically Sypro Orange https://biotium.com/wp-content/uploads/2018/03/Glomelt-...

CETSA Cellular Thermal Shift Assay You need to have an idea of what your target is… Molecules 2021, 26, 6083. https://doi.org/10.3390/molecules26196083  Protein Thermal Stability Use a dye, typically Sypro Orange https://biotium.com/wp-content/uploads/2018/03/Glomelt-flyer.pdf  Thermal Shift But this uses purified protein… How do for target engagement?? https://biotium.com/wp-content/uploads/2018/03/Glomelt-flyer.pdf Example Do they bind RIPK1?  Activity-Based Protein Profiling ABPPà Commonly used to identify covalent inhibitors of enzymes Methods Enzymol. 2014 ; 538: 151–169 Reactive Groups Fluorophosphonate Serine Fluorosulfonate Lysine  ABPP Competition https://www.cravattlab.com/research In Summary For a molecule to become a viable drug you must know what it is doing on a cellular level Non-specific binding leads to off-target effects In order to be FDA approved the MOA typically needs to be well documented. Drugging the Immune System Winter 2024 PharmSci 177/277 Prof. Trader Innate vs Adaptive System The innate immune system is responsible for rapid, non-specific response to any foreign body. A simple example is white blood cells rushing to the site of a laceration to stave off infection. The adaptive immune system is responsible for antigen-specific immune responses and includes certain immune cells (like B cells and T cells) that are designed to recognize and attack that antigen. Immunosuppressant Drugs Immunosuppression is described as a condition of transient or permanent immune system deficiency arising from insults to the immune response with increased resistance to disease and the immune system. Antibody-Drug Conjugates