GSK215 Chemical Properties

Boiling point:

1103.2±65.0 °C(Predicted)

Density 

1.317±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO : 250 mg/mL (253.77 mM; Need ultrasonic)

form 

Solid

pka

13.97±0.40(Predicted)

color 

Off-white to light yellow

InChIKey

ZGSWGXNEXAXEGV-VSAGVCMVNA-N

GSK215 Usage And Synthesis

Uses

GSK215 is a potent and selective PROTAC focal adhesion kinase (FAK) degrader with a pDC50 of 8.4. GSK215 is designed by a binder for the VHL E3 ligase and the FAK inhibitor VS-4718. GSK215 induces rapid and prolonged FAK degradation, giving a long-lasting effect on FAK levels and a marked pharmacokinetic/pharmacodynamics (PK/PD) disconnect[1].

Biological Activity

GSK215 is a potent and selective PROTAC focal adhesion kinase (FAK) degrader. GSK215 is designed by a binder for the VHL E3 ligase and the FAK inhibitor VS-4718. GSK215 induces rapid and prolonged FAK degradation, giving a long-lasting effect on FAK levels and a marked pharmacokinetic/pharmacodynamics (PK/PD) disconnect[1]. GSK215 (0.1-1000 nM; 2 hours) effectively increases the FAK degradation by >90% and determines a DC50 of 1.3 nM[1]. GSK215 (8mg/kg; i.h.) treatment shows the Cmax and tmax values of 526 ng/mL and 0.33 hours, respectively[1].

in vitro

GSK215 (0.1-1000 nM; 2 h) effectively increases the FAK degradation by >90% and determines a DC50 of 1.3 nM in A549 cells. Its induced degradation is proteasome and ubiquitin-dependent. GSK215 (above 100 nM, 6h) primarily reduces kinases CDK7, RPS6KA3, MET, and GAK. This compound (100 nM, 48 h) inhibits migration, invasion, and collagen deposition in A549 cells.

in vivo

storage

Store at -20°C

References

[1]. Law RP, Nunes J, Chung CW, et al. Discovery and Characterisation of Highly Cooperative FAK-Degrading PROTACs [published online ahead of print, 2021 Aug 20]. Angew Chem Int Ed Engl. 2021;10.1002/anie.202109237.

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