GSK215 is a potent and selective PROTAC focal adhesion kinase (FAK) degrader with a p DC 50 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 In Vitro GSK215 (0.1-1000 nM; 2 h) effectively increases the FAK degradation by >90% and determines a DC 50 of 1.3 nM in A549 cells. GSK215 induced degradation is proteasome and ubiquitin dependent. GSK215 (above 100 nM, 6h) reduces primarily kinases CDK7, RPS6KA3, MET and GAK. GSK215 (100 nM, 48 h) inhibits migration, invasion and collagen deposition in A549 cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: A549 cells Concentration: 0.1-1000 nM Incubation Time: 2 h Result: Increased the FAK degradation. Cell Migration AssayCell Line: A549 cells Concentration: 100 nM Incubation Time: 48 h Result: Inhibited cell migration. Cell Invasion AssayCell Line: A549 cells Concentration: 100 nM Incubation Time: 48 h Result: Inhibited cell invasion. In Vivo GSK215 (8 mg/kg; i.h.; once) degrades FAK, and shows the C max and t max values of 526 ng/mL and 0.33 hours, respectively . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male CD1 mice (P878/881A), 7-9 weeks 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 C max and t max were 526 ng/mL and 0.33 hours, respectively. Form:Solid IC50& Target:PROTAC,pDC 50 : 8.4 (FAK)
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GSK215
CAS number：2743427-26-9 molecular formula：C50H59F3N10O6S
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| Chinese alias | - | ||
| English alias | - | ||
| CAS number | 2743427-26-9 | molecular formula | C50H59F3N10O6S |
| molecular weight | 985.13 g/mol | Exact mass | ≥99% |
| PSA | - | logp | - |
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