Uses
TH-257 is a potent inhibitor of LIMK1 and LIMK2 with IC50 values of 84 nM and 39 nM for LIMK1 and LIMK2, respectively, and it can be used as a chemical probe for LIMK1 and LIMK2. TH-257 is an allosteric inhibitor targeting a binding pocket induced by an αC and DFG-out conformation. TH257 is exquisitely selective and no significant activity against the wider kinome has been observed in the KINOMEscan assay at 1 μM[1].
Biological Activity
TH-257 is a potent, type III allosteric LIM-kinase (LIMK1 & LIMK2) inhibitor (LIMK1/2 IC50 in nM = 48/29 by cell-free kinase assay and 250/150 by live cell NanoBRET assay using respective transfectants) th at targets LIMK1/2 DFG-out conformation in a non-ATP-competitive manner and exhibits no significant off-target activity by KINOMEscan assay at 1 μM. TH-263 is a structure analog and the recommended negative control for TH-257. For characterization details of TH-257, please visit the
TH-257 probe summary on the Structural Genomics Consortium (SGC) website.
TH-263 is the negative control for the active probe, TH-257. TH-263 is available from Sigma. To learn more about and purchase TH-263,
click here.
To learn about other SGC chemical probes, visit
sigma.com/sgc
IC 50
LIMK1: 84 nM (IC
50); LIMK2: 39 nM (IC
50)
References
[1] Manetti F. Recent advances in the rational design and development of LIM kinase inhibitors are not enough to enter clinical trials. Eur J Med Chem. 2018 Jul 15;155:445-458. DOI:
10.1016/j.ejmech.2018.06.016[2] Collins R, et, al. Comparative Analysis of Small-Molecule LIMK1/2 Inhibitors: Chemical Synthesis, Biochemistry, and Cellular Activity. J Med Chem. 2022 Oct 27;65(20):13705-13713. DOI:
10.1021/acs.jmedchem.2c00751
