SR7826

SR7826 is a class of bis-aryl urea derived potent, selective and orally active LIM kinase (LIMK) inhibitor with an IC₅₀ of 43 nM for LIMK1. SR7826 is >100-fold more selective for LIMK1 than ROCK and JNK kinases^[1]. IC50 & Target: IC50: 43 nM (LIMK1), 5536 nM (ROCKI) and 6565 nM (ROCKII) In Vitro: In the profiling against a panel of 61 kinases, SR7826 (compound 18b) at 1 μM inhibits only Limk1 and STK16 with ≥80% inhibition. SR7826 is highly efficient in inhibiting cell-invasion/migration in PC-3 cells. SR7826 (compound 18b) inhibits cofilin phosphorylation in A7r5 (IC₅₀ = 470 nM) and PC-3 cells (IC₅₀ < 1 µM)^[1].
SR7826 (1 μM) inhibits contractions of prostate strips, which were induced by electrical field stimulation and inhibits cofilin phosphorylation in prostate tissues and cultured stromal cells (WPMY-1). In WPMY-1 cells, SR7826 causes breakdown of actin filaments and reduced viability^[3]. In Vivo: SR7826 (10 mg/kg; oral gavage; once daily; for 11 days; hAPPJ20 mice) treatment significantly reduces the phosphorylation of cofilin at Ser3. SR7826 also increases both apical and basal thin spine density significantly in hAPPJ20 mice over mock-treated animals^[2].
The plasma pharmacokinetics studies on rats are investigated. After intravenous injection, the PK properties of SR7826 (compound 18b; 1mg/kg) with a Cl of 5.2 mL/min/kg, a T_1/2 of 2.2h, an AUC of 8.4 μM*h and a C_max of 7.7 μM, and has 36% oral bioavailability in rats (oral administration; 2mg/kg)^[1].