IKKβ inhibitor
BI 605906
BI-605906 is a potent and highly selective IKKβ inhibitor (IC50 = 50 nM). in vitro, it has demonstrated effective and consistent inhibition of the phosphorylation of IkBα as well as the expression of ICAM-1. in vivo, BI-605906 has shown dose responsive efficacy in a rat model of collagen-induced arthritis. This compound may be a valuable tool to explore IKKβ-related pharmacology in numerous disease models.
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The serine/threonine kinase IKKβ (inhibitor of I kappa kinase beta, also known as IKK2), serves as the immediate upstream activator of NF-kB mediated transcription and represents as such a key point of convergence for multiple inflammatory pathways induced by cytokines, viral and bacterial infections, antigens, oxidative stress and DNA-damaging agents. Biochemical inhibition of IKKβ has proven efficacious in numerous pharmacology disease models including models of arthritis, inflammatory bowel disease, asthma and tumor metastasis.
Model of BI 605906 bound to IKKβ, based on PDB code: 3RZF9
BI 605906 is a highly selective reversible ATP competitive inhibitor of IKKβ with an IC50 value of 50 nM. BI 605906 has demonstrated mechanistically consistent cell-based inhibition of the phosphorylation of IkBα, the immediate substrate of IKKβ (EC50 0.9 µM) and the expression of downstream NF-kB transcriptional products such as ICAM-1 (EC50 0.7 µM).
Probe name / negative control | BI 605906 | BI-5026 |
| MW [Da, free base]a | 432.5 | 450.5 |
| Inhibition of IKKβ (IC50) [nM] | 50 | >10,000 |
| Inhibition of phospho-IκBα in HeLa cells (EC50) [µM] | 0.9 | n.a. |
| Inhibition of expression of ICAM-1 in HeLa cells (EC50) [µM] | 0.7 | n.a. |
aFor the salt form you will get, please refer to the label on the vial and for the molecular weight of the salt, please refer to the FAQs
Probe name / negative control | BI 605906 | BI-5026 |
| logD @ pH 11 | 1.93 | 2.4 |
| Solubility @ pH 7 [µg/mL] | 41.6 | n.a. |
| Caco-2 permeability AB @pH7.4 [*10-6 cm/s] | 19.7 | n.a. |
| Caco-2 efflux ratio | 1.6 | n.a. |
| Microsomal stability (human/mouse/rat/dog/cyno) [% QH] | 26 / 69 / 28 / 26 / 28 | n.a. |
| Hepatocyte stability (human/rat/dog/cyno) [% QH] | 18 / 52 / 64 / 39 | n.a. |
| Plasma Protein Binding (human/mouse/rat/dog/cyno) [%] | 92 / 92 / 97 / 94 / 94 | n.a. |
| hERG (IC50) [µM] | 25 | n.a. |
| CYP 3A4 (IC50) [µM] | 18 | n.a. |
| CYP 2C8 (IC50) [µM] | n.a. | n.a. |
| CYP 2C9 (IC50) [µM] | 17 | n.a. |
| CYP 2C19 (IC50) [µM] | >30 | n.a. |
| CYP 2D6 (IC50) [µM] | >30 | n.a. |
BI 605906 | MOUSE | RAT | DOG | CYNO |
| Clearance [%QH]a | 33 | 38 | 27 | 18 |
| Mean residence time after iv dose [h]a | 0.8 | 0.9 | 2.4 | 3.4 |
| tmax [h]b | 0.5 | 2.3 | 2.3 | 12 |
| Cmax [nM]b | 2,000 | 490 | 800 | 240 |
| F [%]b | 38 | 38 | 24 | 16 |
| Vss [l/kg]a | 1.5 | 1.5 | 1.2 | 1.6 |
ai.v. dose: mg/kg - to be checked
bp.o. dose: mg/kg - to be checked
BI 605906 shows dose responsive effects in the rat collagen induced arthritis model demonstrating comparable efficacy to anti-TNFa standard etanercept at a dose of 60 mg/kg.
BI-5026 is a close analog of BI 605906 that is inactive on IKKβ and its isoforms IKKα/γ (IC50 > 10 µM).
BI-5026 which serves as a negative control
BI 605906 is a highly selective inhibitor of IKKβ and hits only 3/397 other kinases >50% inhibition at 10 µM: GAK (93%), AAK1 (87%) and IRAK3 (76%).
| SELECTIVITY DATA AVILABLE | BI-605906 | BI-5026 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| PDSP9 | Yes | Yes |
| Invitrogen® | Yes | No |
| DiscoverX® | No | No |
| Dundee | Yes | No |
Download selectivity data:
BI-605906_selectivityData.xlsx
BI-5026_selectivityData.xlsx
Please see reference 7.
BI 605906 is a highly potent and selective inhibitor of IKKβ with an IC50 of 50 nM, that effectively blocks the phosphorylation of IkBα (EC50 0.9 µM) and the expression of ICAM-1 (EC50 0.7 µM) in HeLA cells. Together with the negative control BI-5026, BI 605906 is an excellent tool compound to explore IKKβ related pharmacology in vitro and in vivo.
IKKβ as Therapeutic Intervention Point for Diseases Related to Inflammation
Young E. R. R.
Anti-Inflammatory Drug Discovery 2012, Eds. J. I. Levin, S. Laufer, RSC Publishing, Cambridge.
A Practical Solid Form Screen Approach To Identify a Pharmaceutical Glutaric Acid Cocrystal for Development
Li Z., Yang B.-S., Jiang M., Eriksson M., Spinelli E., Yee N., Senanayake C.
Organic Process Research & Development 2009, 13, 1307-1314
BI 5700, a Selective Chemical Inhibitor of IκB Kinase 2, Specifically Suppresses Epithelial-Mesenchymal Transition and Metastasis in Mouse Models of Tumor Progression
Huber M. A., Maier H. J., Alacakaptan M., Wiedmann E., Braunger J., G. Boehmelt, Madwed J. B., Young E. R. R., Marshall D. R., Pehamberger H., Wirth T., Kraut N., Berg H.
Genes & Cancer 2010, 1, 101-14
When you plan a publication, please use the following acknowledgement:
BI 605906 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.