The document discusses prioritizing hits from high throughput screening (HTS) programs. It provides an overview of HTS and quantitative HTS (qHTS) conducted at the NIH Chemical Genomics Center, including hit selection, cherry picking, and a fragment-based approach. The challenges of identifying active compounds from large amounts of screening data are also addressed.
Integration and Automation in Practice: CI/CD in Mule Integration and Automat...
Prioritizing Scaffolds for Hit Selection in HTS
1. Priori%zing Scaffolds for Hit Selec%on
in High Throughput Screening
Programs
Rajarshi Guha, Dac‐Trung Nguyen
NIH Chemical Genomics Center
6th Indo‐US Workshop on Mathema%cal Chemistry
8th – 10th January, 2010
3. NIH Chemical Genomics Center
Assay development Compound
and op2miza2on Op2miza2on
Small Molecules
Biology Chemistry
NCGC
Informa%cs ACOM
Genome wide RNAi
SAR analysis, method & Automa2on, Compound
tool development management
4. High Throughput Screening
• Assay thousands to
hundreds of thousands
of compounds
– Biochemical, gene%c,
pharmacological assays
• Rapidly iden%fy novel
modulators of biological
systems
• Lots of raw data –
automated analy%cs are
essen%al
5. Hun%ng for Leads
Target Lead Lead Clinical
Iden%fica%on Discovery Op%miza%on Development
HTS
Primary
Confirma%on
• Sensi%vity Screening • Select subset
• Scaling • Fluorescence to follow up • Counter
• High Content • Diversity screen
• Explore SAR
Assay
Cherry Picking
Op%miza%on