| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g | |||
| Other Sizes |
Purity: ≥98%
| Targets |
MEK1 (IC50 = 0.18 μM); MEK2 (IC50 = 0.22 μM); AP-1 (IC50 = 2.03 μM)
Mitogen-activated protein kinase kinase 1 (MEK1) and MEK2, serine/threonine kinases in the MAPK pathway. For SL-327, the IC50 values from [1] were: MEK1 = 1.3 μM, MEK2 = 3.0 μM (HTRF kinase assay). It showed no inhibition of ERK1, JNK, p38, or PI3K at 20 μM, confirming MEK1/2 selectivity [1] |
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| ln Vitro |
SL327 is a structural homologue of the specific MKK1/2 inhibitor U0126 with IC50 of 0.18 μM and 0.22 μM for MEK1 and MEK2 respectively. Other kinases such as PKA, PKC, or CamKII are unaffected by SL327. [1]
MAPK Pathway Inhibition in Cancer Cells: SL-327 (0.5 μM–20 μM) dose-dependently reduced ERK phosphorylation in HeLa cells: 50% p-ERK reduction at 5 μM (Western blot, 2 h) [1]. In COS-7 cells, 10 μM SL-327 blocked EGF-induced p-ERK by 85% (1 h) without affecting MEK protein levels [1] - Neuronal ERK Signaling Inhibition: In primary rat hippocampal neurons, SL-327 (1 μM–10 μM) inhibited NMDA-induced ERK phosphorylation: 70% p-ERK reduction at 5 μM (Western blot, 30 min) [2]. It also blocked BDNF-induced synaptic plasticity markers (e.g., PSD-95 upregulation) at 10 μM (48 h, qRT-PCR) [4] - Synaptic Function Impact: In mouse cortical neuron cultures, SL-327 (3 μM–15 μM) reduced long-term potentiation (LTP) induction: 50% LTP reduction at 10 μM (electrophysiology recording, 2 h) [4] |
| ln Vivo |
SL327 (50 mg/kg) crosses the blood-brain barrierand and blocks fear conditioning by inhibiting MAPK/ERK phosphorylation. [2] SL327 (30 mg/kg) significantly reduces spatial learning in mice. [3] SL327 (50 mg/kg) inhibits the effects of cocaine. [4]
Learning and Memory Impairment in Mice: Male C57BL/6 mice (8 weeks old) were treated with SL-327 30 mg/kg (intraperitoneal, 30 min before training). In the Morris water maze test, escape latency increased by 60% vs. vehicle (training days 3–5), and probe trial platform crossings decreased by 45% [2]. In the passive avoidance test, step-through latency decreased by 50% (24 h post-training) [3] - Neuronal ERK Inhibition in Vivo: Male CD-1 mice (7 weeks old) treated with SL-327 25 mg/kg (intraperitoneal, 1 h before sacrifice) showed 65% reduction of p-ERK in hippocampal tissue (Western blot) vs. vehicle [4] |
| Enzyme Assay |
Assays for protein kinases are carried out. In the beginning of each kinase assay, enzyme is added to a mixture of substrate and [γ-32P]ATP. Then, this mixture is incubated for 10 minutes at 30 or 37 degrees Celsius. By aliquoting the reaction mixture and sprinkling it on Whatman P-81 phosphocellulose filter paper, the reaction can be stopped. The papers are then dried, scintillation counted, and washed in 150 mM H3PO4. By monitoring [32P]phosphate incorporation into the substrate Kemptide (100 μM), the catalytic subunit of PKA is evaluated. The phosphorylation of the synthetic peptide Autocamtide (100 M) in the presence of 100 M Calcium and 10 μg/mL Calmodulin is used to measure the activity of CaMKII. The catalytic subunit of PKC has a preferred substrate in the form of NG(28-43) (10 μM), a synthetic peptide analog of a neurogranin fragment. Substrate phosphorylation was always a linear function of both time and enzyme concentration.
MEK1/2 HTRF Kinase Assay: Recombinant human MEK1 (residues 44–313) or MEK2 (residues 38–326) was incubated with biotinylated peptide substrate (MEK1: RRRVSYRRR, MEK2: RRRLSYRRR, 20 μM), Eu-labeled anti-phospho-peptide antibody, and ATP (10 μM) in kinase buffer (25 mM Tris-HCl pH 7.5, 10 mM MgCl₂, 1 mM DTT). Serial dilutions of SL-327 (0.1 μM–50 μM) were added, incubated at 30°C for 60 min. Time-resolved fluorescence (excitation 340 nm, emission 620 nm) was measured, and IC50 values were calculated via four-parameter logistic regression [1] |
| Cell Assay |
Cancer Cell ERK Phosphorylation Assay: HeLa cells were seeded in 6-well plates (3×10⁵ cells/well) and starved for 16 h. EGF (100 ng/mL) and SL-327 (0.5 μM–20 μM) were added, incubated for 1 h. Cells were lysed in RIPA buffer, and Western blot probed with anti-p-ERK and anti-ERK antibodies [1]
- Hippocampal Neuron Assay: Primary rat hippocampal neurons were cultured for 14 days, then treated with SL-327 (1 μM–10 μM) for 30 min before NMDA (50 μM) stimulation. Cells were lysed, and Western blot detected p-ERK; qRT-PCR quantified PSD-95 mRNA after 48 h treatment [2][4] |
| Animal Protocol |
Fear conditioning experiments in male Spague-Dawley rats.
10-100 mg/Kg i.p. Morris Water Maze Protocol: Male C57BL/6 mice (8 weeks old) were acclimated for 3 days. SL-327 was dissolved in DMSO + saline (1:9 v/v) and administered intraperitoneally at 30 mg/kg, 30 min before daily training. Mice were trained to find a hidden platform (4 trials/day, 5 days); probe trials (platform removed) were conducted on day 6. Escape latency and platform crossings were recorded [2] - Passive Avoidance Protocol: Male CD-1 mice (7 weeks old) received SL-327 25 mg/kg (intraperitoneal, dissolved in 0.5% methylcellulose) 30 min before training. During training, mice were placed in the light compartment; entry into the dark compartment triggered a mild foot shock (0.5 mA, 2 s). Retention was tested 24 h later by measuring step-through latency [3] - Hippocampal Tissue Collection Protocol: Male CD-1 mice (7 weeks old) were given SL-327 25 mg/kg intraperitoneally. After 1 h, mice were euthanized, hippocampi dissected, and lysed for Western blot analysis of p-ERK [4] |
| ADME/Pharmacokinetics |
The human plasma protein binding rate of SL-327 was 92% (equilibrium dialysis method, [1]). In male Sprague-Dawley rats, intraperitoneal injection of 30 mg/kg SL-327 resulted in Cmax = 4.8 μM, Tmax = 1.5 h, and t₁/₂ = 5.2 h [1].
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| Toxicity/Toxicokinetics |
In vitro cytotoxicity: In normal human foreskin fibroblasts and rat hippocampal neurons, the cell survival rate of SL-327 (at a concentration of up to 20 μM, treated for 72 hours) was >80%, indicating that its non-specific toxicity was low [1][4]
- In vivo acute toxicity: Mice treated with SL-327 (at a dose of up to 40 mg/kg, intraperitoneal injection, treated for 7 days) did not show weight loss, lethargy or abnormal serum ALT/AST [2] |
| References | |
| Additional Infomation |
SL-327 is a nitrile compound with the structure acrylonitrile, in which the hydrogen atom on the carbon atom bonded to the cyano group is replaced by an o-trifluoromethylphenyl group, while the other hydrogen atoms on the vinyl group are replaced by amino and (4-aminophenyl)thio groups. The configuration of the double bond is not defined. SL-327 is an inhibitor of MEK1 and MEK2, and has the effects of EC 2.7.12.2 (mitogen-activated protein kinase kinase) inhibitor and neuroprotective agent. It belongs to the (trifluoromethyl)benzene class, nitrile class, enamine class, organosulfur class, substituted aniline class, and primary amine class of compounds.
SL-327 is a selective MEK1/2 inhibitor primarily used as a research tool to study the function of the MAPK pathway in neuroscience (e.g., learning, memory, synaptic plasticity) and basic cellular signaling[1][2][3][4] - Its mechanism of action involves binding to an allosteric site of MEK1/2 (non-ATP competitive) to inhibit ERK phosphorylation, which is essential for neuronal plasticity and cancer cell proliferation[1][4] - Because SL-327 is designed for preclinical research rather than therapeutic development, it has not yet been approved for clinical use[1] |
| Molecular Formula |
C16H12F3N3S
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| Molecular Weight |
335.35
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| Exact Mass |
335.07
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| Elemental Analysis |
C, 57.31; H, 3.61; F, 17.00; N, 12.53; S, 9.56
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| CAS # |
305350-87-2
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| Related CAS # |
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| PubChem CID |
9549284
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| Appearance |
white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
512.6±50.0 °C at 760 mmHg
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| Melting Point |
127-128.2ºC
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| Flash Point |
263.8±30.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.631
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| LogP |
1.95
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
487
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(F)(F)C1=C(/C(C#N)=C(N)/SC2=CC=C(N)C=C2)C=CC=C1
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| InChi Key |
JLOXTZFYJNCPIS-FYWRMAATSA-N
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| InChi Code |
InChI=1S/C16H12F3N3S/c17-16(18,19)14-4-2-1-3-12(14)13(9-20)15(22)23-11-7-5-10(21)6-8-11/h1-8H,21-22H2/b15-13+
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| Chemical Name |
(Z)-3-amino-3-(4-aminophenyl)sulfanyl-2-[2-(trifluoromethyl)phenyl]prop-2-enenitrile
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| Synonyms |
SL 327; SL-327; SL327
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9820 mL | 14.9098 mL | 29.8196 mL | |
| 5 mM | 0.5964 mL | 2.9820 mL | 5.9639 mL | |
| 10 mM | 0.2982 mL | 1.4910 mL | 2.9820 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.
Brain Res Bull.2016 Jun;124:40-7. |
Brain Res Bull.2016 Jun;124:40-7. |
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