SYK inhibitor
BI 1002494
BI 1002494 is a highly potent SYK inhibitor (IC50 = 0.8 nM). It shows a suitable selectivity profile with good kinase specificity, as well as good physicochemical properties and low toxicity. In addition to its excellent target inhibition, its high solubility and metabolic stability make it an excellent tool to explore SYK functions not only in vitro but also in vivo.
More information
SYK propagates signal transduction for a number of immunoreceptor tyrosine-based activation motif–dependent proinflammatory pathways, including Fc receptor, B-cell receptor (BCR), and integrin signaling.
BI 1002494 in complex with SYK (X-ray structure solved at Boehringer Ingelheim).
BI 1002494 inhibits SYK with an IC50 of 0.8 nM. In human whole blood, BI 1002494 inhibits the DNP/BSA (dinitroprusside / bovine serum albumine)-induced expression of CD63 in basophils, as well as the goat anti-human IgD-induced secretion of CD69 in B cells.
| Probe name | BI 1002494 |
| MW [Da]a | 423.46 |
| SYK (50) [nM] | 0.8 |
| CD63 (50) [nM] human whole blood | 115* |
| CD69 (50) [nM] human whole blood | 810** |
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
*N=263
**N=36
| Probe name | BI 1002494 |
| logD @ pH11 | 2.41 |
| Solubility @ pH 7.4 [µg/ml] | 500 |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | 30 |
| Caco-2 efflux ratio | 2.8 |
| Rat hepatocyte clearance [% QH] | 51 |
| Plasma Protein Binding (mouse / rat) [%] | 93 / 95 |
| BI 1002494 | Mouse | Rat |
| Clearence [% QH]a | 40 | 41 |
| Mean residence time after i.v. dose [h]a | 0.4 | 0.9 |
| Vss [L/kg]a | 0.9 | 1.5 |
| F [%]a | 58 | 41 |
a i.v. dose: 0.4 mg/kg, p.o. dose: 2 mg/kg
BI 1002494 showed 90% reduction of BAL (bronchoalveolar lavage) eosinophils in a rat OVA model at 30 mg/kg (b.i.d.). No adverse events were observed in a 13-week mouse toxicology study up to 100 mg/kg (b.i.d.).
With BI-2492 a structurally very similar molecule (diastereoisomer) with an SYK IC50 = 625 nM (780-fold less potent than BI 1002494) is offered which can be used as a negative control.
BI-2492, negative control
Invitrogen® 23/239 kinases hit > 50% INH @ 1 µM
Eurofins Safety Panel 44™: 3/56 targets > 50% INH @ 10 µM (M1 (h): 70%, A1 (h): 63%, A2A (h): 59%)1.
| SELECTIVITY DATA AVILABLE | BI 1002494 | BI-2492 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| Invitrogen® | Yes | No |
| DiscoverX® | Yes | No |
| Dundee | No | No |
Download selectivity data:
BI-1002494_selectivityData_0.xlsx
BI-2492_selectivityData.xlsx
X-ray co-crystal structure solved at Boehringer Ingelheim (unpublished)
Fostamatinib, Entospletenib
BI 1002494 inhibits SYK with high target potency, good cellular potency, and shows good kinase specificity. It is recommended as in vitro and in vivo tool.
BI 1002494, a Novel Potent and Selective Oral Spleen Tyrosine Kinase Inhibitor, Displays Differential Potency in Human Basophils and B Cells
Lamb D. J., Wollin S. L., Schnapp A., Bischoff D., Erb K. J., Bouyssou T., Guilliard B., Strasser C., Wex E., Blum S., Thaler E., Nickel H., Radmacher O., Haas H., Swantek J. L., Souza D., Canfield M., White D., Panzenbeck M., Kashem M. A., Sanville-Ross M., Kono T., Sewald K., Braun A., Obernolte H., Danov O., Schaenzle G., Rast G., Maier G. M., Hoffmann M.
J Pharmacol Exp Ther 2016, 357, 554-561.
Spleen tyrosine kinase inhibition blocks airway constriction and protects from Th2-induced airway inflammation and remodelling
Tabeling C., Herbert J., Hocke A.C., Lamb D.J., Wollin S.L., Erb K.J., Boiarina E., Movassagh H., Scheffel J., Doehn J.M., Hippenstiel S., Maurer M., Gounni A.S., Kuebler W.M., Suttorp N., Witzenrath M.
Allergy 2017, 72, 1061-1072.
The Novel Oral Syk Inhibitor, Bl1002494, Protects Mice From Arterial Thrombosis and Thromboinflammatory Brain Infarction
van Eeuwijk J. M., Stegner D., Lamb D. J., Kraft P., Beck S., Thielmann I., Kiefer F., Walzog B., Stoll G., Nieswandt B.
Arterioscler Thromb Vasc Biol 2016, 36, 1247-1253
When you plan a publication, please use the following acknowledgement:
BI 1002494 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.