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Chemical Structure| 1253186-56-9 Chemical Structure| 1253186-56-9

Structure of GSK-7975A
CAS No.: 1253186-56-9

Chemical Structure| 1253186-56-9

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GSK-7975A is a potent and orally available CRAC channel inhibitor.

4.5 *For Research Use Only !

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Product Details of GSK-7975A

CAS No. :1253186-56-9
Formula : C18H12F5N3O2
M.W : 397.30
SMILES Code : O=C(NC1=NN(CC2=CC=C(O)C=C2C(F)(F)F)C=C1)C3=C(F)C=CC=C3F
MDL No. :MFCD28411366
InChI Key :CPYTVBALBFSXSH-UHFFFAOYSA-N
Pubchem ID :59547990

Safety of GSK-7975A

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

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
human lung mast cells (HLMCs) 1 μM To assess whether Ca2+ influx through Orai channels contributes to KCa3.1 opening, the selective Orai channel blocker GSK-7975A was used. KCa3.1 currents elicited in response to FcεRI-dependent HLMC activation were significantly attenuated with the subsequent addition of 1 μM GSK-7975A. Cell Commun Signal. 2015 Jul 16;13:32
human coronary artery endothelial cells (hCAECs) 10 µmol/L 2 minutes Inhibited thapsigargin-induced Ca2+ influx, indicating that Ca2+ entry is mediated by SOCE and Orai channels. Arterioscler Thromb Vasc Biol. 2024 Nov;44(11):2271-2287
pancreatic acinar cells 10 µM GSK-7975A markedly reduced asparaginase-induced Ca2+ entry and also protected effectively against the development of necrosis. Philos Trans R Soc Lond B Biol Sci. 2016 Aug 5;371(1700):20150423
SU-DHL-4 cells 3 µM 30 minutes GSK-7975A selectively inhibits SOCE without affecting ER Ca2+ content or SERCA2b ATPase activity, and does not reduce BIRD-2-induced apoptosis. Cell Death Discov. 2018 Nov 2;4:101
human primary myoblasts 10 μM GSK-7975A inhibited constitutive Ca2+ entry in myoblasts expressing ORAI1-T184M and -V107M. J Physiol. 2019 Jan;597(2):561-582
HEK-293T cells 10 μM GSK-7975A efficiently blocked the basal Mn2+ 'leak' and SOCE mediated by TAM-associated ORAI1 mutants (V107M and T184M). J Physiol. 2019 Jan;597(2):561-582
mouse urethral smooth muscle cells (USMCs) 1 μM GSK-7975A reduced the frequency, amplitude, and spatial spread of Ca2+ waves in USMCs, indicating the importance of Orai channels in maintaining Ca2+ waves. J Physiol. 2018 Apr 15;596(8):1433-1466
E13 cortical neurons 5 μM Applied from time +60 s and remained present till the end of the recording GSK-7975A reduced the peak amplitude of SOCE by ~50% Front Pharmacol. 2016 Dec 12;7:486
human umbilical vein endothelial cells (HUVEC) 70 μM 24 hours To evaluate the effect of GSK-7975A on HUVEC migration, results showed that GSK-7975A significantly inhibited cell migration. Front Cell Dev Biol. 2021 Mar 4;9:639952
human umbilical vein endothelial cells (HUVEC) 50 and 70 μM 18 hours To evaluate the effect of GSK-7975A on HUVEC tube formation, results showed that GSK-7975A significantly reduced the formation of tube-like structures. Front Cell Dev Biol. 2021 Mar 4;9:639952
airway smooth muscle cells (ASMCs) 1 μM to 100 μM 5 minutes to 10 minutes To evaluate the effect of GSK-7975A on IP3 receptor activation, results showed that GSK-7975A did not affect IP3-induced calcium signaling. J Physiol. 2017 May 15;595(10):3203-3218

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice (SV129) Retinal angiogenesis model Intraperitoneal injection 2.6, 4.0, 7.9, 15.9, and 31.8 mg/kg Injected at postnatal days P3, P4, and P5, and analyzed at P6 To evaluate the effect of GSK-7975A on retinal angiogenesis, results showed that GSK-7975A significantly reduced vessel length and the number of junctions, while increasing lacunarity. Front Cell Dev Biol. 2021 Mar 4;9:639952
Mice Precision-cut lung slices (PCLS) Perfusion 1 μM to 100 μM Continuous exposure for 5 to 10 minutes To evaluate the effect of GSK-7975A on airway contraction and calcium oscillations, results showed that GSK-7975A could fully relax airway contraction and stop calcium oscillations. J Physiol. 2017 May 15;595(10):3203-3218
Mouse Mouse urethral smooth muscle In vitro perfusion 1 μM GSK-7975A reduced urethral contractions induced by phenylephrine, suggesting that Orai channels function effectively as receptor-operated channels. J Physiol. 2018 Apr 15;596(8):1433-1466

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.52mL

0.50mL

0.25mL

12.58mL

2.52mL

1.26mL

25.17mL

5.03mL

2.52mL

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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