| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
SR7826 targets LIM kinase 1 (LIMK1), a serine/threonine kinase that plays a critical role in actin cytoskeleton dynamics by phosphorylating and inactivating cofilin. It is a potent and selective inhibitor with an IC50 of 43 nM. It displays >100-fold selectivity over ROCK1 and ROCK2, as well as JNK kinases (over 400-fold).
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| ln Vitro |
Only Limk1 and STK16 were inhibited with ≥80% inhibition by SR7826 (compound 18b) at 1 μM in an investigation against a panel of 61 kinases. SR7826 is an efficient inhibitor of PC-3 cell migration and invasion. In A7r5 (IC50 = 470 nM) and PC-3 cells (IC50 < 1 µM), SR7826 (Compound 18b) suppresses cofilin phosphorylation [1]. SR7826 (1 μM) suppresses cofilin phosphorylation in prostate tissue and cultured stromal cells (WPMY-1) as well as prostatic strip contraction brought on by electric field stimulation. SR7826 fragments actin filaments and lowers viability in WPMY-1 cells [3].
In vitro, SR7826 inhibits LIMK1 with an IC50 of 43 nM. It is >100-fold more selective for LIMK1 than ROCK and JNK kinases. It inhibits cofilin phosphorylation in A7r5 cells and suppresses migration and invasion of PC-3 prostate cancer cells. These activities demonstrate its potent and selective LIMK1 inhibitory profile. |
| ln Vivo |
Treatment with SR7826 (10 mg/kg; oral gavage; once daily; for 11 days; hAPPJ20 mice) significantly reduced cofilin Ser3 phosphorylation. SR7826 also dramatically increased apical and basal spine density in hAPPJ20 mice compared with mock-treated animals [2]. Plasma pharmacokinetic studies were performed in rats. After intravenous injection, PK characteristics of SR7826 (compound 18b; 1mg/kg), Cl is 5.2mL/min/kg, T1/2 is 2.2h, AUC is 8.4μM*h, Cmax is 7.7μM, and oral bioavailability in rats The concentration is 36% (orally; 2mg/kg) [1].
In vivo, SR7826 is an orally active LIMK inhibitor. Its ability to inhibit LIMK1 and downstream signaling has been demonstrated in preclinical studies. However, specific details of in vivo efficacy studies, such as the animal models used and the dosing regimens, are not extensively detailed in the available literature. |
| Enzyme Assay |
The in vitro kinase assay for SR7826 measures its ability to inhibit LIMK1 activity. These cell-free assays use purified recombinant LIMK1 and a peptide substrate. The compound's inhibitory potency (IC50) is determined by measuring the reduction in kinase activity. Selectivity is assessed by testing the compound against a panel of other kinases.
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| Cell Assay |
In vitro cellular assays for SR7826 assess its effects on LIMK1-mediated signaling. Cells are treated with SR7826, and cofilin phosphorylation is measured by Western blot. Its effects on cell migration and invasion are assessed using Boyden chamber or scratch wound assays. These assays demonstrate the compound's functional activity in a cellular context.
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| Animal Protocol |
Animal/Disease Models: hAPPJ20 mice (6 oral years) [2]
Doses: 10 mg/kg Route of Administration: po (oral gavage); one time/day; for 11 days Experimental Results: Dramatically diminished cofilin Ser3 (a LIMK1 substrate) Phosphorylation. In vivo animal studies for SR7826 are conducted in models of cancer to evaluate its antitumor efficacy. Its ability to inhibit LIMK1 and suppress tumor growth and metastasis is assessed. However, specific details of these studies are not extensively detailed in the available literature. |
| ADME/Pharmacokinetics |
SR7826 is orally active. Its pharmacokinetic properties support oral administration. As a small molecule kinase inhibitor, it is absorbed and distributed throughout the body. However, detailed parameters such as half-life and bioavailability are not extensively detailed in the available literature. It is intended for research use only.
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| Toxicity/Toxicokinetics |
Specific toxicity data for SR7826 are not extensively detailed in the available literature. As a LIMK1 inhibitor, its toxicity profile is likely related to its mechanism of action. However, its selectivity for LIMK1 over other kinases may contribute to a favorable safety profile. It is intended for research purposes only.
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| References |
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| Additional Infomation |
SR7826 is a potent, selective, and orally active LIMK1 inhibitor. It is a valuable research tool for studying the role of LIMK1 in actin cytoskeleton dynamics, cell migration, and cancer. It is not approved for clinical use and is intended for research purposes only.
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| Molecular Formula |
C22H21N5O2
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|---|---|
| Molecular Weight |
387.434444189072
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| Exact Mass |
387.169
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| CAS # |
1219728-20-7
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| PubChem CID |
45381385
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| Appearance |
White to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.738
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| LogP |
2.53
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
533
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CNC2=NC=NC(=C12)C3=CC=C(C=C3)NC(=O)N(CCO)C4=CC=CC=C4
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| InChi Key |
WQAGVQVBDHOHRD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H21N5O2/c1-15-13-23-21-19(15)20(24-14-25-21)16-7-9-17(10-8-16)26-22(29)27(11-12-28)18-5-3-2-4-6-18/h2-10,13-14,28H,11-12H2,1H3,(H,26,29)(H,23,24,25)
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| Chemical Name |
1-(2-hydroxyethyl)-3-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]-1-phenylurea
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~258.11 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.45 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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