[CAS NO. 1219728-20-7] SR7826
PRODUCTS SPECIFICATIONS [1219728-20-7]
DESCRIPTION [1219728-20-7]
Overview
| MDL | MFCD29081182 |
|---|---|
| Molecular Weight | 387.43 |
| Molecular Formula | C22H21N5O2 |
| SMILES | O=C(NC1=CC=C(C2=C3C(NC=C3C)=NC=N2)C=C1)N(CCO)C4=CC=CC=C4 |
Summary
IC50 & Target
|
LIMK1 43 nM (IC 50 ) |
ROCKI 5536 nM (IC 50 ) |
ROCKII 6565 nM (IC 50 ) |
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 (IC
50
= 470 nM) and PC-3 cells (IC
50
< 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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | hAPPJ20 mice (6-mouth-old) [2] |
| Dosage: | 10 mg/kg |
| Administration: | Oral gavage; once daily; for 11 days |
| Result: | Significantly reduced the phosphorylation of cofilin at Ser3, a LIMK1 substrate. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 258.11 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.5811 mL | 12.9056 mL | 25.8111 mL |
| 5 mM | 0.5162 mL | 2.5811 mL | 5.1622 mL |
| 10 mM | 0.2581 mL | 1.2906 mL | 2.5811 mL |
References
- [1] Yan Yin, et al. Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors. J Med Chem. 2015 Feb 26;58(4):1846-61.
- [2] Benjamin W Henderson, et al. Pharmacologic inhibition of LIMK1 provides dendritic spine resilience against β-amyloid. Sci Signal. 2019 Jun 25;12(587):eaaw9318.
- [3] Qingfeng Yu, et al. Inhibition of human prostate smooth muscle contraction by the LIM kinase inhibitors, SR7826 and LIMKi3. Br J Pharmacol. 2018 Jun;175(11):2077-2096.