Thermal Shift Assay Services

Learn More About BellBrook Labs' Assay Services

Thermal Shift Assay Services

BellBrook offers TSA services for hundreds of enzyme targets aimed to advance your lead discovery program. Thermal shift assays are an important small molecule drug discovery tool to evaluate compound-target engagement and characterize protein structure. The assay confirms if a compound engages the protein by evaluating shifts in protein melting temperature upon addition of a probe compound.

BellBrook is a small custom shop. We are responsive, knowledgeable, and offer quicker turnaround times than the larger CROs, saving you time and money.  Our assay conditions are customizable to suit your needs and you will directly collaborate with real scientists throughout the process. Contact us today to see if BellBrook's thermal shift assay services will advance your small molecule research. 

BellBrook Labs is with you throughout the drug discovery process.

Drug Discovery Process

Thermal Shift Assay Services

Thermal shift assays, or differential scanning fluorimetry (DSF), confirm a compound's engagement with a target protein by evaluating shifts in protein melting temperature. The assay is performed in a high-throughput format in 96-well plates.

Proteins are subject to a temperature gradient in the presence of a fluorescent probe, SYPROTM, that is quenched by water. As the proteins unfold, their exposed hydrophobic domains bind the dye resulting in increased fluorescence until they began to aggregate and exclude the dye with a corresponding decrease in fluorescence.

Our TSA services can help:

  • Characterize protein stability and optimal buffer conditions
  • Determine the protein's melting temperature (TM)
  • Evaluate compound-protein binding
TSA Principle 300 x 250 px

Example TSA Services Using Human cGAS Protein

Below includes example data of our thermal shift assay services using human cGAS protein. Our services are available for 100's of different enzyme targets. Please contact us today to see if we can accelerate your target program.

Determination of Optimal Assay Conditions

Our scientists will determine the optimal conditions to create a robust assay signal using minimal enzyme concentrations. Here, we performed a titration at varying cGAS concentrations from 20 - 95°C. The lowest cGAS concentration that produced a robust assay signal was 1.25 μM using optimized buffer conditions.

cGAS Titration at Varying Concentrations

cGAS Enzyme Titration for TSA

cGAS Enzyme Titration at 1.25 μM

cGAS Titration for TSA at 1.25 μM

Confirm Compound-Target Binding Interactions

BellBrook scientists will perform TSAs for your target protein and compound to determine a change in protein melting temperature. Shifts in a protein's melting temperature upon addition of a compound indicate compound-target interaction. Here, we see a shift in the melting temperature of cGAS with 2 inhibitors, an internally discovered compound 993, and known cGAS inhibitor, PF-06928215.

cGAS Thermal Shift (993 Compound)

Thermal Shift Assay Services using 993 Compound

ΔTM = 10°C

cGAS Thermal Shift (PF-06928215 Compound)

Thermal Shift Assay Services using PF-06928215 Compound

ΔTM = 14°C

How Do Our Assay Services Work?

Choose Your Target

If you don't see your target listed below, please inquire. We may still be able to help! Click on a target below to learn more.

Example Target Families
Protein Kinases
Lipid Kinases
Carbohydrate Kinases
ATPases
Acetyltransferases
HDACs
GTPases, GAPs, GEFs
Phosphodiesterases
Helicases
Ligases/Synthetases
Glycosyltransferases

Example Targets
cGAS
AMPK
WRN Exonuclease
CD73
JAK1
WRN Helicase
CD39
JAK3
POLQ
DDX3
EZH2
METTL3/METTL14
ENPP1
PKR
MLL4
IKK-beta
MAPK8
PRMT4
CD38
ADK
PRMT5
PARG
TREX1
RIPK1
TBK1
GALNT2
RIPK2
NSP13
GALNT3
p97
NUDT5
OAS1
KHK

Talk To A Scientist

Let's talk science. We'd like to learn more about your target, your goals, and how we can accelerate your program.

We'll Do The Work

Send us your compounds. Our scientists will take care of the rest. Assays will be performed in a timely manner at our lab in Madison, WI. 

Quickly Provide a Report & Support

We'll provide a full report including the raw data and results of the experiments. We can keep things as simple or complex as you like.

Download Our App Note

Why Choose BellBrook Labs to Accelerate Your Program?

Leveraging BellBrook's services expertise will save you time and money. Your project will be handled by the same BellBrook scientists who developed the Transcreener assays and have optimized them for more than 100 different enzymes, including kinases, ATPases, GTPases, glycosyltransferases, ligases/synthetases, and phosphodiesterases. We will tailor our efforts to meet your specific needs. For example, minimizing consumption of limited reagents or enabling simultaneous screening for inhibitors and activators. And we will work fast. If your target enzyme is in good shape, we can generally complete the services within two to four weeks. 

Advantage of BellBrook's Drug Discovery Services

Contact Us to Learn More

Please fill out the form below. We will respond quickly to get the conversation moving and learn how we can help. We keep things discrete, confidential, and professional.

Related Resources

BellBrook Labs
1232 Fourier Drive, Suite 115
Madison, Wisconsin 53717 USA
(608) 443-2400

info@bellbrooklabs.com

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