The probe and control may be requested here.
| Probe | Negative control | |
 |  | |
TP-061 | TP-061N |
Bad response to refrigeration 2 (Brr2) is a 200 kDa protein and a member of DEXD/H-box helicase constituting a part of U5 snRNP. Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex, which is a critical step in the activation of spliceosome.
Takeda in collaboration with the University of Oxford and OICR has developed TP-061 as a potent inhibitor of Brr2. TP-061 exhibits IC50 of 21 nM in the ADP-Glo ATPase assay and 480 nM in the unwinding assay. Target binding is confirmed by SPR with Kd of 22 nM. The enantiomer, TP-061N, serves as an ideal negative control with IC50 of 84 mM in the ATPase assay.
TP-061 shows excellent selectivity over closely-related helicases, with no inhibition of eIF4A1, eIF4A3 and DHX29 up to 100 mM.
Additional selectivity over 300 kinases using in-house assay showed none with inhibition > 50% when tested at 1 mM.
Ito et. al. Discovery of spiro[indole-3,20-pyrrolidin]-2(1H)-one based inhibitors targeting Brr2, a core component of the U5 snRNP. Bioorg Med Chem., 2017, 25, 4753-4767, https://doi.org/10.1016/j.bmc.2017.07.017.