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Chemical Structure| 942206-85-1 Chemical Structure| 942206-85-1

Structure of GSK1016790A
CAS No.: 942206-85-1

Chemical Structure| 942206-85-1

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GSK1016790A is a potent and selective transient receptor potential vanilloid 4 (TRPV4) channel agonist that can elicit Ca2+ influx and elevate intracellular Ca2+ in HEK cells.

Synonyms: GSK101

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Product Citations

Product Citations

Wu, Xingyi ; Zhang, Ying ; Yi, Fan ; Geng, Zaijun ; Guo, Miaomiao ; Ling, Xiao , et al.

Abstract: Daemonorops draco Bl. extract and its active ingredients can remove blood stasis and promote muscle and wound healing and are widely used in skin health and other fields. Modern pharmacological studies have demonstrated that this extract exerts excellent anti-inflammatory effects beneficial for skin barrier repair. However, the mechanism of action and monomeric components of D. draco remain unclear. Seven active monomers (XJ-1~XJ-7) were extracted and purified from D. draco. The successful construction of the HaCaT was achieved through the detection of IL-1β and TNF-α expressions in UVB-irradiated HaCaT cells. Based on this cellular model, (2 S)-5-methoxy-6-methylflavan-7-ol (XJ-2) was determined to be the best-screened monomer. The effects of XJ-2 on the production of reactive oxygen species (ROS) and Ca2+ in HaCaT cells were investigated using fluorescent probes and flow cytometry, respectively. The impact of XJ-2 on the expression of crucial proteins within the pathway was examined via immunofluorescence and western blotting. The expression levels of downstream inflammatory factors, namely IL-1β and TNF-α, were detected through PCR. The effects of XJ-2 on the expression of skin barrier-related factors filaggrin (FLG), aquaporin 3 (AQP-3), and claudin1 (CLDN1) were investigated using PCR, immunofluorescence, and western blotting. Based on these findings, we comprehensively examined the mechanisms underlying the anti-inflammatory and barrier repair effects of XJ-2. XJ-2 primarily protected the internal structure and function of the cells by inhibiting the mass production of and Ca2+ inflow. XJ-2 exerts anti-inflammatory effects by regulating the key proteins of the NF-κB/IKKα pathway and reducing the expression of inflammatory factors. XJ-2 repairs skin barrier damage by regulating multiple factors. Compound XJ-2 from D. draco exerts excellent anti-inflammatory and barrier repair effects, possesses great potential for the treatment of skin diseases, and can be used as a dermatological drug to repair skin barrier damage.

Keywords: Daemonorops draco Bl. ; (2S)-5-methoxy-6-methylflavan-7-ol (XJ-2) ; HaCaT ; ; Anti-inflammation ; Skin barrier

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Product Details of GSK1016790A

CAS No. :942206-85-1
Formula : C28H32Cl2N4O6S2
M.W : 655.61
SMILES Code : O=C(C1=CC2=CC=CC=C2S1)N[C@H](C(N3CCN(C([C@@H](NS(=O)(C4=CC=C(Cl)C=C4Cl)=O)CO)=O)CC3)=O)CC(C)C
Synonyms :
GSK101
MDL No. :MFCD12912413
InChI Key :IVYQPSHHYIAUFO-VXKWHMMOSA-N
Pubchem ID :23630211

Safety of GSK1016790A

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

Isoform Comparison

Biological Activity

Description
GSK1016790A is characterized as a highly potent and selective agonist for the transient receptor potential vanilloid 4 (TRPV4) channel. It triggers Ca2+ influx and increases intracellular Ca2+ levels in HEK cells[1].[2].

In Vitro:

Cell Line
Concentration Treated Time Description References
Neonatal rat ventricular myocytes 500 nM 30 minutes To investigate the effect of TRPV4 activation on CaMKII phosphorylation, results showed that GSK790A markedly increased the expression of p-CaMKII, but this effect was blocked by TRPV4 antagonist GSK3874 or removal of extracellular Ca2+. PMC9224988
BeWo cells 20 nM 10 minutes Activation of TMEM16F via TRPV4, leading to intracellular Ca2+ increase and phospholipid scrambling PMC9236608
BeWo cells 0.2 nM transient exposure Local activation of TMEM16F, leading to reversible PS exposure PMC9236608
Murine neutrophils 1 nM, 10 nM, 100 nM 10 minutes Measure the increase in intracellular calcium, results showed a dose-dependent increase in intracellular calcium with GSK1016790A. PMC11116040
Smooth Muscle Cells (SMCs) 200 μM 50 minutes To evaluate the effect of H2O2 exposure on smooth muscle cells, results showed that SMC death was significantly higher in young male mice compared to old male mice. PMC11113258
Endothelial Cells (ECs) 200 μM 50 minutes To evaluate the effect of H2O2 exposure on endothelial cells, results showed that EC death was significantly lower than SMC death, and neither age nor sex affected EC death. PMC11113258

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Sprague-Dawley rats LPS-induced cystitis model Intravesical instillation 10 mM Once every 48 hours for 4 days To investigate the effect of TRPV4 activation on LPS-induced cystitis, results showed that co-instillation of GSK1016790A with LPS improved bladder inflammation, reduced mast cell numbers, and suppressed LPS-induced bladder pain-related behavior and increased voiding frequency. PMC9812943
C57BL/6 mice Old and young mice In vitro culture 200 μM 50 minutes To evaluate the effect of H2O2 exposure on mouse cerebral arteries, results showed that old mice and female mice had increased resilience to acute oxidative stress, with reduced SMC death. PMC11113258

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.53mL

0.31mL

0.15mL

7.63mL

1.53mL

0.76mL

15.25mL

3.05mL

1.53mL

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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