PROTAC TBK1 degrader-2 

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; K_d=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].

IC50: 1.3 nM (TBK1), 8.7 nM (IKKε)^[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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1093.18

C₅₃H₇₄BrN₉O₉S

2052306-13-3

Solid

White to off-white

O=C(NCC1=CC=C(C2=C(C)N=CS2)C=C1)[C@H]3N(C([C@H](C(C)(C)C)NC(COCCCOCCCCOCCCOC4=CC=C(NC5=NC=C(Br)C(NCCCN(C(C6CCC6)=O)C)=N5)C=C4)=O)=O)C[C@H](O)C3

Room temperature in continental US; may vary elsewhere.

• [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.  [Content Brief]