Discovery Technology Access Grant (D-TAG)

Discovery Technology Access Grant (D-TAG)

CETSA Unbiased Drug Profiling

$6,000 Match

 

CETSA-MS enables proteome-wide assessment of compound–protein interactions by leveraging the principle that ligand binding stabilizes protein structure against thermal denaturation. In cell lysates treated with a small molecule, proteins are exposed to a controlled temperature gradient. Proteins not bound to ligands unfold and precipitate with increasing heat, while those stabilized by direct binding remain soluble at higher temperatures. Following centrifugation, the remaining soluble protein fraction is analyzed by quantitative mass spectrometry.

Unlike traditional affinity-based or overexpression-dependent methods, CETSA-MS performed in lysate captures native protein conformations and post-translational modifications, providing a physiologically relevant view of compound engagement. The resulting thermal profiles allow for the identification of both primary targets and off-targets based on shifts in melting temperature (Tm) and changes in relative protein abundance across the temperature series. This unbiased, label-free approach enables compound selectivity profiling, and early risk assessment in drug discovery workflows.

CDD is offering a 50% cost match—up to $3,000—for compounds submitted for unbiased CETSA profiling through our contract research organization (CRO) Pelago Bioscience, the pioneers of the CETSA platform. The total cost of CETSA profiling is $6,000 per compound (tested at two concentrations), with CDD offsetting half of this amount to help accelerate your drug discovery efforts.

To be considered, please submit a brief proposal outlining your project goals, compounds for testing, current drug discovery stage, and any relevant preliminary data. Proposals will be evaluated based on scientific merit and feasibility. This program is designed to support lead optimization by providing early, critical selectivity and engagement data.

 

Eligibility criteria. Investigators with a faculty appointment at Washington University.

Submission deadline. June 25, 2025.   Grant notification: by July 1, 2025.

Award term. The funds will be used within two weeks of the notification.

Expectation. The CETSA Profiling D-TAG is intended as a strategic “hand-up” to generate key preliminary data on compound selectivity and target engagement. This data is expected to strengthen future applications for extramural funding. Projects that successfully complete CETSA profiling under this program may be eligible to apply for follow-on support to further build the data package needed to improve the competitiveness of external grant proposals.

Reporting. Investigators will be surveyed annually for 3 years after the award expires to capture the return on investment (e.g., publications, grant submissions, other outcomes) for the D-TAG program.

Application process:

  • Download application form here.
  • Submit completed application along with a current Biosketch or CV to Ron Dolle.

 

Submission deadline: Wednesday, June 25, 2025.