SGK3-PROTAC1

SGK3-PROTAC1 is a proteolysis-targeting chimera (PROTAC) containing the serum/glucocorticoid-regulated kinase 3 (SGK3) inhibitor 308-R conjugated to VHL ligand 1 (Cay-21591) via an alkyl linker with two PEG units. It inhibits SGK3, SGK1, and p70 ribosomal S6 kinase 1 (S6K1, IC50s = 0. 0. and 1. µM, respectively) but selectively induces degradation of SGK3 over SGK1 and S6K1 in HEK293 cells when used at concentrations ranging from 0. to 3 µM. SGK3-PROTAC1 (0. µM) potentiates cell growth inhibition induced by GDC-0941 (Cay-11600) in CAMA-1 and ZR-75-1 breast cancer cells. It also reduces SGK3 levels, sodium-dependent phosphate transporter 1 (PiT-1) levels, and calcium deposition induced by high levels of inorganic phosphate (Pi) in primary mouse vascular smooth muscle cells (VSMCs) when used at a concentration of 2. µM. InChI: InChI=1S/C57H73FN10O11S2/c1-37-10-19-46(58)48(28-37)81(73,74)66-42-17-15-41(16-18-42)52-63-53-45(31-61-65-53)55(64-52)79-34-44-33-67(21-23-78-44)20-8-6-7-9-22-75-24-25-76-26-27-77-35-49(70)62-51(57(3,4)5)56(72)68-32-43(69)29-47(68)54(71)59-30-39-11-13-40(14-12-39)50-38(2)60-36-80-50/h10-19,28,31,36,43-44,47,51,66,69H,6-9,20-27,29-30,32-35H2,1-5H3,(H,59,71)(H,62,70)(H,61,63,64,65)/t43-,44-,47+,51-/m1/s1 InChIKey: RTFQFPZKDYMMMJ-RIAKQDHQSA-N SMILES: FC(C=CC(C)=C1)=C1S(=O)(NC2=CC=C(C3=NC(OC[C@@H]4OCCN(C4)CCCCCCOCCOCCOCC(N[C@H](C(N5C[C@H](O)C[C@H]5C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)C(C)(C)C)=O)=C8C=NNC8=N3)C=C2)=O