University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

About Small Molecule Discovery

The Small Molecule Discovery Shared Resource (SMD) collaborates with academics, government labs, and pharmaceutical companies to develop unique chemical probes and drug leads that address unmet medical needs in cancer.

Services

Hit identification (Screening)

Small molecule hits are identified using a variety of experimental screening technologies, including:

  • biochemical screens measuring a specific activity
  • cell assays using primary cells and cell lines
  • small model organism screens using high-content imaging
  • fragment screening by surface plasmon resonance and nuclear magnetic resonance (NMR)
  • site-directed disulfide trapping (aka tethering).

High-throughput screening (HTS)

A common approach for identifying compounds for further optimization. HTS uses robotic automation to allow testing of thousands to millions of compounds against one assay.

Compound libraries

The SMD houses more than 200,000 molecules, including libraries based on diverse compounds, approved drugs, and bioactives with known mechanisms of action.

Fragment discovery

A complementary technology to high-throughput screening (HTS), fragment-based drug discovery has proven successful for many drug targets that are recalcitrant to traditional functional assays.

Tethering

A site-directed fragment discovery method wherein bespoke libraries of disulfide-containing compounds are screened for binding to a native or engineered cysteine residue.

Hit-to-lead medicinal chemistry

Our chemists are available to collaborate on programs on a personnel-support basis and can support grantwriting and fundraising efforts.