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Chemical Structure| 305350-87-2 Chemical Structure| 305350-87-2

Structure of SL327
CAS No.: 305350-87-2

Chemical Structure| 305350-87-2

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SL327 is a cell-permeable vinylogous cyanamide that acts as a selective inhibitor of MEK-1 and MEK-2 (IC50 = 0.18 and 0.22 μM respectively).

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Product Details of SL327

CAS No. :305350-87-2
Formula : C16H12F3N3S
M.W : 335.35
SMILES Code : N#CC(C1=CC=CC=C1C(F)(F)F)=C(N)SC2=CC=C(N)C=C2
MDL No. :MFCD06411432
InChI Key :JLOXTZFYJNCPIS-FYWRMAATSA-N
Pubchem ID :9549284

Safety of SL327

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of SL327

MAPK

Isoform Comparison

Biological Activity

Target
  • MEK2

    MEK2, IC50:0.22 μM

  • MEK1

    MEK1, IC50:0.18 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
Mixed neuron–glia cortical cell cultures 30 µM 30 minutes SL327 significantly reduced heme oxygenase (HO) activity in cultures Neuropharmacology. 2009 Apr;56(5):922-8.
MGE cells 10 µM 7 days To assess the effect of MEK inhibitor SL327 on LHX6 expression, found that SL327 restored LHX6 expression in Nf1 cKO CINs Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):6189-6195.
Recombinant HO-1 and HO-2 30 µM SL327 had no significant effect on the activity of recombinant HO-1 or HO-2 Neuropharmacology. 2009 Apr;56(5):922-8.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Rats Ethanol withdrawal anxiety model Intracerebroventricular injection 1 µg/5 µl Administered 30 min prior to each of two stress sessions Blocked stress facilitation of ethanol withdrawal anxiety Brain Behav Immun. 2011 Jun;25 Suppl 1(Suppl 1):S146-54
Rat Aging rat model Microinjection 10 μM Single administration Inhibition of ERK1/2 signaling, downregulation of GSK-3β (Ser9) phosphorylation Mar Drugs. 2019 Mar 15;17(3):168
Rats Morphine dependence model Intraperitoneal injection 100 mg/kg Once, 1 hour before naloxone injection To evaluate the effect of SL327 (a selective MEK inhibitor) on TH phosphorylation at Ser31 during morphine withdrawal. Results showed that SL327 significantly reduced the phosphorylation levels of TH at Ser31. Br J Pharmacol. 2008 Sep;155(1):73-83
Rats Morphine dependence model Intraperitoneal injection 100 mg/kg 1 hour before administration SL327 (a selective inhibitor of MEK) at doses that reduced the augmented pERK levels in the PVN, did not attenuate the rise in pCREB immunoreactivity or plasma corticosterone secretion. Br J Pharmacol. 2011 Jun;163(4):857-75
Sprague-Dawley rats Morphine dependence model Intraperitoneal injection 100 mg/kg Single dose, 1 hour before morphine withdrawal SL327 significantly inhibited the increase in phosphorylation of ERK1/2 and c-Fos expression in cardiac tissues induced by morphine withdrawal. Br J Pharmacol. 2007 Jul;151(6):787-97
Mice Neonatal mouse hypoxic-ischemic brain injury model Intraperitoneal injection 133 μg/g Single injection, administered 20 min before or 1 h after HI insult SL327 significantly reduced cell death and microglial activation, showing neuroprotective effects in both pre- and post-treatment J Physiol. 2018 Dec;596(23):6043-6062
Nude mice Subcutaneous tumor model Intraperitoneal injection 3 mg/kg/day Once daily, continuous treatment Inhibited tumorigenicity of melanoma cells Front Cell Dev Biol. 2020 Dec 17;8:607757
Mice Conditioned place preference (CPP) model Intraperitoneal injection 30 mg/kg Single administration, 1 hour before cocaine reexposure Blockade of the ERK pathway during drug reexposure erases previously acquired cocaine-induced CPP and associated protein phosphorylation responses Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2932-7
Mice Myshkin mouse model Intraperitoneal injection 30 mg/kg Acute administration SL327 reduced the total distance traveled in the open field, duration on the open arms, and exploratory head dips in the EPM in Myk/+ mice. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18144-9
Klotho mutant mice Klotho mutant mouse model Intraperitoneal injection 5 or 10 mg/kg Injected 30 min before the memory trial SL327 significantly counteracted melatonin-mediated increases in ERK phosphorylation, Nrf2 nuclear translocation and DNA-binding activity, and GCL mRNA expression, and reversed melatonin-mediated up-regulation of the GSH/GSSG ratio and memory enhancement. Int J Neuropsychopharmacol. 2014 Dec 30;18(6):pyu105
Mice Wild-type mice Intraperitoneal injection 50 and 100 mg/kg Single administration SL327 inhibits morphine-induced locomotor activity in a dose-dependent manner Neuropsychopharmacology. 2011 Feb;36(3):551-8
Mice TgNTRK3 mouse model Intraperitoneal injection 50 mg/kg Single dose SL327 inhibited ERK phosphorylation, blocking NT3-induced rescue of fear extinction memory Neuropsychopharmacology. 2017 Jan;42(2):462-472
CD-1 mice Conditioned place preference (CPP) and locomotor activity measurements Intraperitoneal injection 50 mg/kg Administered 1 hour before SL327 completely abolished the MDMA-induced conditioned place preference and hyperlocomotor activity, indicating a critical role of the ERK pathway in these behavioral responses. Br J Pharmacol. 2003 Nov;140(5):831-8
Rats Formalin-induced acute inflammation model Intraperitoneal injection 50 mg/kg Single dose, 30 minutes before formalin injection Inhibition of ERK activity reduced formalin-induced p-ERK, p-MSK1, and p-H3S10, demonstrating that spinal p-MSK1 and p-H3S10 were at least partly downstream of ERK signalling. Pain. 2016 Nov;157(11):2594-2604

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.98mL

0.60mL

0.30mL

14.91mL

2.98mL

1.49mL

29.82mL

5.96mL

2.98mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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