Lab Exam 2 Study Guide Exam Questions with Verified Answers

Describe the qualities of an ideal drug target. - ANSWER-an enzyme with a critical function in a biochemical pathway of central importance to the bacterial cell What were the sources of drug discovery in first generation approaches? - ANSWER-Based on antimicrobial activity or systematic screens of soil and fungal extracts for bacterial growth inhibition Why did the first generation approaches begin to fail? - ANSWER-Ran into the law of diminishing returns when screens for growth inhibition began returning antibiotics that had already been developed How many compounds are typically tested in a high-throughput screen? - ANSWER-typically 10,000s to 100,000s of molecules Why do large-scale in vitro screens typically fail? - ANSWER-that inhibition of a target in a test tube turned out to be a very poor predictor of whether the compound could get into bacterial cells and successfully kill it or limit its growth. How are compounds identified in hyperpermeability experiments useful to scientists developing antibiotics when the cells are not representative of the cells that are present in human infections? - ANSWER-The use of hyperpermeable cells with an hypersusceptible target will allow even weakly active molecules to be detected, providing potentially important information to direct the optimization of structures by modeling and chemical modification. What information is necessary for a compound to be declared a "hit?" - ANSWER-including for example literature surveys, active natural products, high-throughput screening of chemical libraries (including whole-cell phenotypic screens like the Discovery Lab approach), and virtual screening. Explain the difference between a drug with a therapeutic index (TI) of 22 and a drug with a TI of 183 in terms of toxicity. - ANSWER-A high TI value is more desirable because it indicates that the compound is likely to be less toxic than a compound with a lower TI What is the benefit of developing a TPP (target product profile) early in the development of a drug? - ANSWER--defines the key features of the drug to be developed bearing in mind probable clinical needs -will be used to make an initial evaluation of the economic potential of the drug if it were to succeed all the way to the market