hit to lead screening

Question 1

what is hts?

Answer 1

HTS: Rapidly tests large compound libraries against biological targets using automated systems.

Question 2

what is virtual screening?

Answer 2

Virtual Screening: Computationally predicts active compounds based on target structure or ligand properties.

Question 3

What are the assay formats for htss?

Answer 3

Biochemical Assays: Measure enzyme activity or target binding.
Cell-Based Assays: Assess cellular responses (e.g., signalling, proliferation).
Reporter Assays: Use detectable markers (e.g., fluorescence).

Question 4

what are the advances in structural biology and computaional techniques

Answer 4

Techniques like X-ray crystallography, cryo-EM, and AI modelling enable detailed target structures for virtual screening.

Question 5

What are the pitfalls of hts?

Answer 5

False positives/negatives.
High cost and time requirements.
Limited chemical diversity in libraries.

Question 6

Describe fragment based screening

Answer 6

Origins: Identifies small molecular fragments binding weakly to targets.
Assays: Biophysical techniques like NMR, X-ray crystallography, or surface plasmon resonance (SPR)

Question 7

Describe hit to lead discovery

Answer 7

Optimises initial “hits” into more potent, selective “lead” compounds.
Techniques: Medicinal chemistry, SAR studies, and computational modelling.
Place in Drug Discovery: Transition step between screening and preclinical testing.