TH251 

TH251 is a LIMK1 and LIMK2 inhibitor with IC₅₀s of 52 nM and 47 nM against LIMK1 and LIMK2, respectively. TH251 binds to inactive αC-out and DFG-out LIMK1 conformations, inhibits unphosphorylated LIMK1 and LIMK2 enzymatic activity, and exhibits unchanged potency despite PAK-mediated phosphorylation of either kinase. TH251 can be used for the research of cancers, glaucoma, and CNS diseases^[1][2].

TH251 (Compound 22) (45-180 min) potently inhibits LIMK2 (pIC₅₀ = 7.90) and PAK-phosphorylated LIMK2 (pIC₅₀ = 8.19) with greater potency than against LIMK1 and PAK-phosphorylated LIMK1 in purified enzyme assays^[1].
TH251 potently inhibits human LIMK1 kinase activity (IC₅₀ = 52 nM) and human LIMK2 kinase activity (IC₅₀ = 47 nM) in a mass spectrometry-based kinase assay using CFL1 as the substrate^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

TH251 (1-50 μM) (Compound 22) rescues hyperactive crawling and elevated neuromuscular junction bouton number in dFMR1 mutant Drosophila larvae, normalizing these Fragile X syndrome-related phenotypes^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

394.49

C₂₂H₂₂N₂O₃S

1622059-04-4

O=C(C1=CC=C(C=C1)S(=O)(=O)NC=2C=CC=CC2)N(CC=3C=CC=CC3)CC

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. 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.  [Content Brief]

  [2]. Mathea, S; et al. LIM Domain Kinase 1 (LIMK1), Human Kinase Domain; A Target Enabling Package. University of Oxford, 2017 Jun 2.