PROTAC TBK1 degrader-2

• CAT Number: I037033
• CAS Number: 2052306-13-3
• Molecular Formula: C53H74BrN9O9S
• Molecular Weight: 1093.18
• Purity: ≥95%
• Synonyms: (2S,4R)-1-[(2S)-2-[[2-[3-[4-[3-[4-[[5-bromo-4-[3-[cyclobutanecarbonyl(methyl)amino]propylamino]pyrimidin-2-yl]amino]phenoxy]propoxy]butoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
• InChI: InChI=1S/C53H74BrN9O9S/c1-36-46(73-35-58-36)38-16-14-37(15-17-38)31-56-49(66)44-30-41(64)33-63(44)51(68)47(53(2,3)4)60-45(65)34-71-28-10-26-69-24-6-7-25-70-27-11-29-72-42-20-18-40(19-21-42)59-52-57-32-43(54)48(61-52)55-22-9-23-62(5)50(67)39-12-8-13-39/h14-21,32,35,39,41,44,47,64H,6-13,22-31,33-34H2,1-5H3,(H,56,66)(H,60,65)(H2,55,57,59,61)/t41-,44+,47-/m1/s1
• InChIKey: QMGHHBHPDDAGGO-IIWOMYBWSA-N
• SMILES: CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)COCCCOCCCCOCCCOC4=CC=C(C=C4)NC5=NC=C(C(=N5)NCCCN(C)C(=O)C6CCC6)Br)O

PROTAC TBK1 degrader-2 is a Ligands for Target Protein for PROTAC. PROTAC TBK1 degrader-2 is a potent degrader based on the serine/threonine kinase TANK-binding kinase 1 (TBK1) (DC50=15 nM; Kd=4.6 nM) with a maximum efficiency of 96%. PROTAC TBK1 degrader-2 also targets to IkB kinase IKKε (IC50=8.7 nM), with low selectivity over TBK1 (IC50=1.3 nM)[1].
PROTAC TBK1 degrader-2 (compound 3i) (100 nM) mediates degradation of TBK1 abrogated by VHL ligand 2 (10 μM) or proteasome inhibitor Carfilzomib (HY-10455) (100 nM)[1].
PROTAC TBK1 degrader-2 (0-3 μM) exhibits poor selectivity for TBK1 over IKKε (IC50 of 1.3 nM vs 8.7 nM), but has no effect on the levels of IKKε, at concentrations of more than 50-fold above its TBK1 DC50[1].
PROTAC TBK1 degrader-2 (100 nM; 300 M; 72 h) is not synthetically lethal in K-Ras mutant versus wild type cells[1].

Reference

[1]. Crew AP, et al. Identification and Characterization of Von Hippel-Lindau-Recruiting Proteolysis Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1. J Med Chem. 2018 Jan 25;61(2):583-598.
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