| Chemical Properties | Back Directory | [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 |
| Hazard Information | Back Directory | [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]
GSK215 (8 mg/kg; i.h.; once) degrades FAK, and shows the Cmax and tmax values of 526 ng/mL and 0.33 hours, respectively[1]. | Animal Model: | Male CD1 mice (P878/881A), 7-9 weeks[1] | | Dosage: | 8 mg/kg | | Administration: | Single subcutaneous injection | | Result: | Caused a rapid and profound degradation of FAK in liver over time, with a maximal degradation of ~85% being achieved within 18 h. Endogenous FAK was found to still be reduced by ~60% at 96 h post-dose.The Cmax and tmax were 526 ng/mL and 0.33 hours, respectively.
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| [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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