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PROTAC SGK3 degrader-1 (SGK3-PROTAC1) is a potent SGK3 degrader, it is a PROTAC conjugate of the 308-R SGK inhibitor with the VH032 VHL binding ligand, targeting SGK3 (Serum/Glucocorticoid Regulated Kinase Family Member 3). SGK3-PROTAC1 (0.3 μM) induces 50% degradation of endogenous SGK3 within 2 h, with maximal 80% degradation observed within 8 h, accompanied by a loss of phosphorylation of NDRG1, an SGK3 substrate. Low doses of SGK3-PROTAC1 (0.1−0.3 μM) restores sensitivity of SGK3 dependent ZR-75-1 and CAMA-1 breast cancer cells to Akt and PI3K inhibitors, whereas the cis epimer analogue incapable of binding to the VHL E3 ligase has no impact. SGK3-PROTAC1 suppresses proliferation of ZR-75-1 and CAMA-1 cancer cell lines treated with a PI3K inhibitor more effectively than could be achieved by a conventional SGK isoform inhibitor.
Int J Biol Sci. 2025 Mar 19;21(6):2462-2475.
The SGK3/GSK3β/β-catenin signaling promotes breast cancer stemness and confers resistance to alpelisib therapy
PROTAC SGK3 degrader-1 purchased from AbMole
| Molecular Weight | 1157.38 |
| Formula | C57H73FN10O11S2 |
| CAS Number | 2381320-35-8 |
| Solubility (25°C) | DMSO ≥ 90 mg/mL |
| Storage | -20°C, sealed |
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