SD-36

SD-36 is a potent and selective degrader for STAT3 and STAT3 mutants and highly recommended as a chemical probe. STAT3 is a transcription factor implicated in various human diseases such as cancer. It has been difficult to drug due to the peptidic nature of ligands that bind to its SH2 domain, as well as the difficulty in achieving adequate selectivity for the STAT3 SH2 domain compared to that of other STAT family members. SD-36 addresses this need, and provides a useful tool for binding and removing STAT3 via proteasomal degradation. It demonstrates > 20-fold selectivity for binding STAT3, and >100-fold selectivity for degrading STAT3 compared to other members of the STAT family. It is also exquisitely selective for STAT3 compared to other proteins outside the STAT family according to proteome-wide selectivity analyses. Lastly, SD-36 can be delivered intravenously into mice and shows sustained degradation even out to 72 hours after dosing. For use in cells, I recommend concentrations in the range of 100nM – 5uM depending on the cell line. For use in mice, I recommend dosing at 25 – 100 mg/kg intravenously.

Recommend dose-response in cell line of interest and note the (p)STAT3 and CRBN status (by western blot for example).  Note: At 10 micromolar the recommended control SD-36Me has an effect on STAT3 dimer similar to that of 5 micromolar of the benchmark inhibitor SI-109.