LFA-1 antagonist
BI-1950
BI-1950 is a highly potent and selective lymphocyte function-associated antigen-1 (LFA-1) inhibitor. It prevents the binding of ICAM-1 to LFA-1 and, as a result, inhibits the production of IL-2 as demonstrated in human whole blood and PBMCs. BI-1950 shows an attractive DMPK profile and was tested in vivo in a proof-of-concept mouse model for delayed-type hypersensitivity, where it inhibited swelling in a dose-dependent manner and showed full efficacy at an oral dose of 3 mg/kg.
More information
The integrin LFA-1 (lymphocyte function-associated antigen-1) is a receptor present on lymphocytes that plays, together with its major ligand ICAM-1 (intercellular adhesion molecule 1), an important role in immune cell function1,3,4.
X-Ray structure of LFA-1 with an analogue of BI-1950 (solved at Boehringer Ingelheim)
BI-1950 inhibits theh binding o LFA_1 to ICAM-1 with a KD value of 9 nM andn the production of IL-2 in humabn PBMC and whole blood with an IC50 value of 3nM and 120 nM, resectively.
| Probe name / negative control | BI-1950 | BI-9446 |
| MW [Da]a | 646.5 | 602.5 |
| Inhibition of LFA-1 binding to ICAM-1 KD [nM]b | 9 | >1000 |
| Inhibition of SEB-induced production of IL-2 in human PBMC IC50 [nM]c | 3 | >1000 |
| Inhibition of SEB-induced production of IL-2 in human whole blood IC50 [nM]c | 120 | 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
bBinding assay
cSEB: staphylococcal enterotoxin B
| Probe name / negative control | BI-1950 | BI-9446 |
| logD @ pH 11 | 4.7 | 5.9 |
| Solubility @ pH 6.8 [µg/mL] | 1.2 | 0.1 |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | 13 | n.a. |
| Caco-2 efflux ratio | 2 | n.a. |
| Microsomal stability (human/mouse/rat) [% QH] | 13 / 12 / 6 | n.a. |
| hERG [inh. % @ 1 µM] | 6.7 | n.a. |
| BI-1950 | Mouse | Rat |
| Clearance [% QH]a | 5 | 1.1 |
| Vss [L/kg] | 1.3 | 2.7 |
| Mean residence time after i.v. dose [h] | 7.2 | 6.5 |
| F [%]b | 154 | 21 |
ai.v. dose: 1 mg/kg
bp.o. dose: 10 mg/kg
BI-1950 shows an attractive DMPK profile and was tested in a proof-of-concept model in vivo. As BI-1950 demonstrates greater than 250-fold selectivity for human over mouse LFA-1 as assessed in paired assays that measure the inhibition of IL-2 production in SEB-stimulated human PBMC and mouse splenocytes (SEB: staphylococcal enterotoxin B), a trans vivo model for delayed type hypersensitivity (DTH) in SCID mice was used.5 After injection of human PBMCs into the footpad of SCID mice and stimulation with a specific antigen (tetanus toxoid, TT), the DTH response is quantified by measuring the footpad swelling. BI-1950 inhibited swelling in a dose dependent manner and showed full efficacy at a dose of 3 mg/kg p.o..
BI-9446, negative control of BI-1950
The close analog BI-9446 can be used as negative control for in vitro studies with much weaker affinity to LFA-1 (> 1µM).
In an external selectivity screen at Eurofins Safety Panel 44™ BI-1950 hit 4/47 targets > 50% Inhibition @ 10 µM. See supplementary information for details.
BI-1950 shows >1000-fold selectivity against the most closely related b2-integrin Mac-1 and b1-integrin function.
| SELECTIVITY DATA AVILABLE | BI-1950 | BI-9446 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| PDSP9 | Yes | Yes |
| Invitrogen® | No | No |
| DiscoverX® | No | No |
| Dundee | No | No |
Download selectivity data:
BI-1950_selectivityData.xlsx
BI-9446_selectivityData.xlsx
No X-ray structure is available for BI-1950 but for the structurally related compound ( 17 d in J. Med. Chem. 2004;47:5356)2.
BI-1950 is a highly potent inhibitor of LFA-1 and an excellent molecule for testing biological hypotheses in vitro and in vivo.
2 D structure formats available
LFA-1 (lymphocyte function-associated antigen-1) antagonist | BI-1950.png
LFA-1 (lymphocyte function-associated antigen-1) antagonist | BI-1950.smiles
LFA-1 (lymphocyte function-associated antigen-1) antagonist | BI-1950.sdf
Negative control | BI-9446.png
Cutting Edge: A Small Molecule Antagonist of LFA-1-Mediated Cell Adhesion
Kelly T. A., Jeanfavre D. D., McNeil D. W., Woska J. R. Jr, Reilly P. L., Mainolfi E. A., Kishimoto K. M., Nabozny G. H., Zinter R., Bormann B. J., Rothlein R.
J. Immunol. 1999, 163, 5173.
Second-Generation Lymphocyte Function Associated Antigen-1 Inhibitors: 1H-Imidazo[1,2-α]imidazol-2-one Derivatives
Wu J. P., Emeigh J., Gao D. A., Goldberg D. R., Kuzmich D., Miao C., Potocki I., Qian K. C., Sorcek R. J., Jeanfavre D. D., Kishimoto K., Mainolfi E. A., Nabozny G. Jr., Peng C., Reilly P., Rothlein R., Sellati R. H., Woska J. R. Jr., Chen S., Gunn J. A., O'Brien D., Norris S. H., Kelly T. A.
J. Med. Chem. 2004, 47, 5356.Regiocontrolled synthesis of highly-functionalized fused imidazoles: a novel synthesis of second generation LFA-1 inhibitors
Frutos R. R, Johnson M.
Tetrahedron Lett. 2003, 44, 6509.
Asymmetric Synthesis of LFA-1 Inhibitor BIRT2584 on Metric Ton Scale
Wang X. J.,Frutos R. P., Zhang L., Sun X., Xu Y., Wirth T., Nicola T., Nummy L. J., Krishnamurthy D., Busacca C. A., Yee N., Senanayake C. H.
Org. Process Res. Dev. 2011, 15, 1185.
When you plan a publication, please use the following acknowledgement:
BI-1950 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.