Aurora B inhibitor
BI 831266
BI-831266 is a potent and selective Aurora B inhibitor (IC50 = 42 nM). This compound is suitable for both in vitro and in vivo experiments. It has been shown to inhibit cellular proliferation in vitro with an IC50 of around 10 nM. in vivo, it was tested in xenograft models and tumor growth inhibition was observed.
More information
Aurora B belongs to the highly conserved Aurora family, a family of 3 nuclear serine-threonine kinases. Aurora A, B and C play important roles in maintaining genetic stability and fidelity of mitosis of cells1.
The Aurora kinases share a highly conserved catalytic domain but different subcellular localizations. Aurora kinases contain mainly two domains: 1) NH2-terminal regulatory domain, 2) COOH-terminal catalytic domain. The three auroras A, B, and C share great homology in the catalytic domain.
Phosphorylation at threonine within the activation loop is necessary for kinase activity2.
Aurora B regulates chromosomal orientation, chromosome condensation, spindle assembly, and cytokinesis1. It plays a direct role in histone H3 phosphorylation.>
The overexpression of Aurora B has been observed in several tumor types and has been linked with a poor prognosis of cancer patients3.
BI 831266 bound to Aurora B, as observed by X-ray (structure solved at Boehringer Ingelheim)
BI 831266 is a potent Aurora B inhibitor with an IC50 of 42 nM.
in vitro activity table
| PROBE NAME / NEGATIVE CONTROL | BI 831266 | BI-1282 |
| MW [Da, free base]a | 528.1 | 505.5 |
| Aurora B binding (IC50) [nM] | 42 | >4000 |
| Aurora B binding Invitrogen® Panel (IC50) [nM] | 25 | - |
| Histone H3 phosphorylation modulation as biomarker (IC50) [nM] | 51 | n.d. |
| H460 polyploide phenotype > 50% [nM] | 14 | n.d. |
| H460 tumor cell proliferation inhibition (IC50) [nM] | 11 | n.d. |
a For 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 831266 | BI-1282 |
| log P/D @ pH | ||
| Solubility @ pH 7.4 [µg/mL] | 875 | n.d. |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | 6.1 | n.d. |
| Caco-2 efflux ratio | 6.0 | n.d. |
| Human hepatocyte clearance [% QH] | 12 | n.d. |
| Plasma Protein Binding human [%] | 48 | n.d. |
| PROBE NAME | BI 831266 | ||
| Species | mouse | rat | dog |
| Dose i.v./p.o. [mg/kg] | 10 / 10 | 4 / 10 | 0.5 / 2 |
| Clearance [% QH]a | 71 | 45 | 19 |
| Mean residence time after i.v. dose [h]a | 0.6 | 1.4 | 1.0 |
| F [%]b | 34 | 20 | 9 |
| Vss [L/kg]a | 2.6 | 3.6 | 1.1 |
a i.v. dose: mg/kg
b p.o. dose: mg/kg
BI-1282 (negative control)
The diaminopyrimidine BI-1282 with the N-methyl group to block kinase hinge- binding can be used as an in vitro negative control.
Extensive external screens available (also see supplementary data):
Invitrogen® panel: 47 kinases screened @ 1 µM
Selected IC50 measured @ Invitrogen®:
AURKB IC50 = 25 nM; AURKC IC50 = 37 nM; RET IC50 = 169 nM; EPHA2 IC50 = 181 nM; STK6 IC50 = 183 nM; AMPK A1B1G1 IC50 = 2.95 µM; AMPK A2B1G1 IC50 = 3.88 µM
Dundee panel: 87 kinases screened @ 1 and 3 µM
DiscoverX® panel: 468 kinases screened @ 1 µM
Eurofins Safety Panel 44™ External screen covering 68 targets @ 10 µM
| SELECTIVITY DATA AVILABLE | BI 831266 | BI-1282 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| Invitrogen® | Yes | No |
| DiscoverX® | Yes | No |
| Dundee | Yes | No |
Download selectivity data:
BI-831266_selectivityData_0.xlsx
BI-1282_selectivityData.xlsx
The X-ray crystal structure of Aurora B/INCENP in complex with the -CF3 analog of the probe (BI 811283) is available (PDB code: 5K3Y)4
AMG-900, AZD1152, AT9283, VX-680(MK-0457), PHA-680632, PHA-739358, CYC-116
BI 831266 is a potent and selective Aurora B inhibitor that inhibits cell proliferation and could be used as a tool compound for testing biological hypotheses.
Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive Inhibitor of MEK and Aurora Kinases
Sini P., Gurtler U., Zahn S. K., Baumann C., Rudolph D., Baumgartinger R., Strauss E., Haslinger C., Tontsch-Grunt U., Waizenegger I. C., Solca F., Bader G., Zoephel A., Treu M., Reiser U., Garin-Chesa P., Boehmelt G., Kraut N., Quant J., Adolf G. R.
Mol. Cancer Ther. 2016, 15, 2388-2398.
When you plan a publication, please use the following acknowledgement:
BI 831266 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.