Autotaxin (ATX) inhibitor
BI-2545
BI-2545 is a highly potent human ATX inhibitor. This compound is suitable for both in vitro and in vivo studies. In human whole blood, BI-2545 inhibited ATX with an IC50 of 29 nM, while in rat whole blood the IC50 was 96 nM. In rats, an LPA reduction of up to 90% was observed after a single oral dose at 10 mg/kg.
More information
Autotaxin (ATX) is a secreted phosphodiesterase that hydrolyzes the abundant phospholipid lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA). Recent studies suggest that the ATX-LPA axis is highly implicated in a number of pathophysiological diseases including inflammation, cancer and idiopathic pulmonary fibrosis.
BI-2545 bound to ATX (X-ray structure solved at Boehringer Ingelheim)
| PROBE NAME / NEGATIVE CONTROL | BI-2545 | BI-3017 |
| MW [Da, free base]a | 527.4 | 407.4 |
| hATX LPA IC50 [nM] | 2.2 | 8900 |
| rat whole blood IC50 [nM] | 96 | n.d. |
| human whole blood IC50 [nM] | 29 | 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-2545 |
| logD @ pH 11 | 1.1 |
| Solubility @ pH 6.8 [µg/mL] | <1 |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | 9.3 |
| Caco-2 efflux ratio | 1.4 |
| Human hepatocyte clearance [% QH] | 22 |
in vivo DMPK parameters table
| PROBE NAME | BI-2545 |
| Rat PKa | |
| Clearance [% QH)] | 10 |
| Mean Residence time after i.v. dose [h] | 2.1 |
| Vss [L/kg] | 0.9 |
| Rat PKb | |
| Cmax [nM] | 918 |
| tmax [h] | 1.7 |
| F [%] | 30 |
a i.v. dose: 0.52mg/kg
b p.o. dose: 52 mg/kg
Chemical structure of the negative control BI-3017
| SELECTIVITY DATA AVILABLE | BI-2545 | BI-3017 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| PDSP7 | Yes | Yes |
| Invitrogen® | No | No |
| DiscoverX® | No | No |
| Dundee | No | No |
Download selectivity data:
ATX_BI-2545_selectivityData.xlsx
BI-3017_selectivityData.xlsx
The X-ray co-crystal structure of ATX with BI-2545 will be published (paper submitted).
See reference 1
BI-2545 is highly potent inhibitor of Autotaxin (ATX) which can be used to test hypotheses in vitro and in vivo. We also offer BI-3017 as inactive control.
Discovery, Structure-Activity Relationship, and Binding Mode of an Imidazo[1,2-a]pyridine Series of Autotaxin Inhibitors
Joncour A., Desroy N., Housseman C., Bock X., Bienvenu N., Cherel L., Labeguere V., Peixoto C., Annoot D., Lepissier L., Heiermann J., Hengeveld W. J., Pilzak G., Monjardet A., Wakselman E., Roncoroni V., Le Tallec S., Galien R., David C., Vandervoort N., Christophe T., Conrath K., Jans M., Wohlkonig A., Soror S., Steyaert J., Touitou R., Fleury D., Vercheval L., Mollat P., Triballeau N., van der Aar E., Brys R., Heckmann B.
J. Med. Chem. 2017, 60, 6480-6515.
Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design
Jones S. B., Pfeifer L. A., Bleisch T. J., Beauchamp T. J., Durbin J. D., Klimkowski V. J., Hughes N. E., Rito C. J., Dao Y., Gruber J. M., Bui H., Chambers M. G., Chandrasekhar S., Lin C., McCann D. J., Mudra D. R., Oskins J. L., Swearingen C. A., Thirunavukkarasu K., Norman B. H.
ACS Med. Chem. Lett. 2016, 7, 857-861.
Discovery of BI-2545: A Novel Autotaxin Inhibitor That Significantly Reduces LPA Levels in Vivo ACS
Kuttruff C. A., Ferrara M., Bretschneider T., Hoerer S., Handschuh S., Nosse B., Romig H., Nicklin P., Roth G. J.
Med. Chem. Lett. 2017, 8, 1252-1257
When you plan a publication, please use the following acknowledgement:
BI-2545 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.