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BAY-985

Protein target name:
TBK1, IKBKEMechanism of action:
InhibitorRecommended Concentration for use in cells:
up to 1 uM
Reviewer suggested Concentration for use in cells:
200 nM
Probe Availability
Probe Information
In vitro validation
Potency:
IC502 nM (L) and 18 nM (H) TBK1; 2 nM IKBKE
Potency assay:
TR-FRET-based kinase activity inhibition assays using recombinant human enzymes. PDB ID for probe-target interaction (3D structure):
6RSRStructure-activity relationship:
Yes see DOI: 10.1021/acs.jmedchem.9b01460Probe Selectivity in Vitro:
High kinase selectivity for TBK1 and IKBKE (selectivity ratio > 100-fold, except for FLT3 with IC50 = 123 nM (75x) and MAP2K5 IC50 = 847 nM (518x) (both Bayer internal kinase panel); STK17A Kd = 74 nM (49x) and MAP3K19 Kd = 9.6 nM (6x) (both DiscoverX); STK17A IC50 = 310 nM (105x) (Eurofins kinase panel)
In cell validation
Potency in cells:
IC50312 nM TKB1; 1735 nM IKBKE
Potency assay (cells):
NanoBRET;
anti-proliferative activity;
no activity in MDA-MB-231 xenograft.
Probe Selectivity in Cell:
Clean in Lead Profiling Screen (Eurofins-Panlabs)
In vivo validation
Organism:
MouseDose:
0.3 mg/Kg IVup to 200 mg/KgRoute of delivery:
IntravenousIntraperitonealSystemic clearance:
0.5 and 1.7 L/h/KgFraction of probe bound to plasma protein:
11 %External Resources
Available data:
SGC additional analysis