BI 1950

BI 1950 : Inhibitor of ITGAL

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Probe BI 1950 is in the process of SERP review.

Please continue to check back for new reviews and commentary.

Information

ITGAL

Inhibitor

100 nM

Additional Data

SGC image SGC Chemical Probe Collection

Probe Availability:

MCULE

In Vitro Validations

Uniprot ID: P20701

Target Class: Integrin

Target SubClass: --

Potency: Kd

Potency Value: 9 nM

Potency Assay: ITGAL binding assay

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Integrin alpha-L, CD11A, ITGAL, ITAL_HUMAN, LFA-1A ...

DOI Reference: 10.1002/jlcr.3698

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Selectivity within target family: Selective (>1000 fold) against closely related ITGB2 and ITGB1. Selectivity outside target family: Cerep Panel at 10 µM; BI-1950 hit 4/47 off targets > 50 %, all four (CA+/DHPSI/RA, CA+/PAASITE, NA+/SITE2/RA and THRO SYN(HU)) : IC50 > 3 µM; Clean GPCR scan

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Lymphocyte function-associated antigen 1 (LFA-1) is is a heterodimeric glycoprotein with non-covalently linked subunits ITGAL (CD11a) and ITGB2 (CD18), that is expressed in all leukocytes and involved in cellular adhesion and costimulatory signaling. BI-1950 binds selectively to the I domain of ITGAL thus inhibiting the interaction between LFA-1 and its major ligand ICAM-1 (intercellular adhesion molecule 1) with high specificity and good potency. The close analog BI-9446 can be used as negative control for in vitro studies as it shows weaker affinity to ITGAL (> 1µM). A co-crystal structure of close analogue compound 17d with ITGAL

(last updated: 3 Mar 2022 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

BI-1950 has both strong binding affinity to the target protein LFA1 and potent activity in IL-2 cellular assays using both PBMCs and whole blood. The plasma protein binding is high, so this should be considered when serum/albumin is present in assay media. There is a strong data pack around selectivity which indicates that no concerning off-target activity has been identified. When considering the use of BI-1950 in rodent efficacy models it is important to take into consideration 250-fold weaker activity in IL-2 assays using mouse splenocytes compared with human PBMCs. Although the PK parameters have been disclosed, I do not believe that total or free drug levels have been shared which would be useful.

(last updated: 11 Mar 2022 )