PROTAC SGK3 degrader-1

• CAT Number: I018110
• CAS Number: 2381320-35-8
• Molecular Formula: C57H73FN10O11S2
• Molecular Weight: 1157.38
• Purity: ≥95%
• Synonyms: (2S,4R)-1-[(2S)-2-[[2-[2-[2-[6-[(2R)-2-[[6-[4-[(2-fluoro-5-methylphenyl)sulfonylamino]phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxymethyl]morpholin-4-yl]hexoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
• 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: CC1=CC(=C(C=C1)F)S(=O)(=O)NC2=CC=C(C=C2)C3=NC4=C(C=NN4)C(=N3)OCC5CN(CCO5)CCCCCCOCCOCCOCC(=O)NC(C(=O)N6CC(CC6C(=O)NCC7=CC=C(C=C7)C8=C(N=CS8)C)O)C(C)(C)C

PROTAC SGK3 degrader-1 (SGK3-PROTAC1), is a potent SKG3 degrader based on von Hippel-Lindau ligand. PROTAC SGK3 degrader-1 (0.3 μM) induces 50% degradation of endogenous SGK3 within 2 hours, with maximal 80% degradation observed within 8 hours, accompanied by a loss of phosphorylation of NDRG1 (an SGK3 substrate)[1].
PROTAC SGK3 degrader-1 (SGK3-PROTAC1) (0.3 μM, 4 weeks) in combination with GDC0941 inhibits cell growth in CAMA-1 or ZR-75-1 cells[1].
PROTAC SGK3 degrader-1 (0.1 μM, 48 h) reduces SGK3 levels by 65% without effecting SGK1, SGK2, or S6K1 in HEK293 cells[1].
PROTAC SGK3 degrader-1 (1-10 μM, 48 h) moderate reduces S6K1 levels in HEK293 cells[1].
PROTAC SGK3 degrader-1 ( >0.1 μM, 8 h) reduces NDRG1 phosphorylation in HEK293 cells, and induces degradation of SGK3, but not SGK1 or S6K in CAMA-1 and ZR-75-1cells [1].

Reference

[1]. Tovell H, et al. Design and Characterization of SGK3-PROTAC1, an Isoform Specific SGK3 Kinase PROTAC Degrader. ACS Chem Biol. 2019 Sep 20;14(9):2024-2034.
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