BGJ-398

Inhibitor of FGFR1, FGFR2, FGFR3, FGFR4

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 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.

Information

FGFR1
FGFR2
FGFR3
FGFR4

Inhibitor

Up to 100 nM

Probe Availability:

In Vitro Validations

Uniprot ID: P11362

Target Class: Kinase

Target SubClass: TK

Potency: IC50

Potency Value: 0.9 nM

Potency Assay: Kinase assay

PDB ID for probe-target interaction (3D structure): 3TT0

Target aliases:

Fibroblast growth factor receptor 1, HBGFR, FLT2, ...

DOI Reference: 10.1021/jm2006222

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): BGJ-398 was tested against an in-house panel of 76 kinases

Probe Selectivity in Vitro:

BGJ-398 was tested against CYP450 enzymes 3A4, 2C9, 2C19, 2D6 and 1A2 all with IC50 > 10 uM

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This probe is a potent and selective inhibitor of FGFR1/2/3 (though less potent against FGFR4). It acts as an adequate in vitro and in vivo inhibitor tool for these kinases.

(last updated: 23 May 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This compound is a pan FGFR inhibitor in the nM range with other kinases only being inhibited at high (triple digit) nM or low uM in cells. I think this probe is the best so far though, ideally, there would be separate probes for FGFR 1-4.

(last updated: 1 Jun 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This probe has single-digit nM potency on FGFR1,2,3 in both in vitro biochemical and cell-based assays. It shows potency against only 76 other kinases assayed with most significant activity on FGFR4 (60 nM) and VEGFR2 (180 nM). Its selectivity against several related kinases remains unknown, however, (e.g. FLT1, CSFR, c-Kit, etc), which leads to some concern. Control of FGFR-driven tumor xenograft seen at doses 5 mg/kg - 30 mg/kg in multiple models. The preferred probe for FGFR4 is BLU9931 (Cancer Discovery, Hagel et al. 2015).

(last updated: 7 Jun 2016 )