AZD4547

Inhibitor of FGFR1, FGFR2, FGFR3

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(1 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 AZD4547 is in the process of SERP review.

Please continue to check back for new reviews and commentary.

Information

FGFR1
FGFR2
FGFR3

Inhibitor

30-100 nM

Probe Availability:

In Vitro Validations

Uniprot ID: P11362

Target Class: Kinase

Target SubClass: TK

Potency: IC50

Potency Value: 0.2 nM

Potency Assay: Enzymatic assay

PDB ID for probe-target interaction (3D structure): 4V05, 4WUN

Target aliases:

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

DOI Reference: 10.1158/0008-5472.CAN-11-3034

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 KDR 24 nM, FGFR4 165 nM, IGFR 581 nM

Probe Selectivity in Vitro:

Selectivity was examined against a diverse panel of representative human kinases and AZD4547 shown to inhibit recombinant VEGFR2 (KDR) kinase, No enzyme inhibition was detected against ALK, CHK1, EGFR, MAPK1, MEK1, p70S6K, PDGFR, PKB, Src, Tie2, and PI3-kinase; FGFR4 cellular kinase activity (IC50 = 142 nmol/L). cellular KDR and IGFR ligand–induced phosphorylation (IC50 values of 258 and 828 nmol/L, respectively), representing approximately 20- and 70-fold selectivity over cellular FGFR1.

Potency in cells, off target : IC50 KDR 258 nM, FGFR4 165 nM, IFGR 828 nM

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

This probe has a long history of use to study FGFR signaling, especially with regards to its importance in various tumors. Cancer-cell profiling revealed that AZD4547 is quite specific in killing only FGFR1-amplified cell lines. In vivo, strong tumor regression was observed in patient-derived xenograft models (containing FGFR1 amplification) at ~10mg/kg (oral administration for ~2 weeks).

(last updated: 20 Dec 2021 )

SERP+ Ratings

In Cell Rating

In Model Organisms

SERP+ Comments:

Established selectivity is excellent for 3 combined kinases vs kinome with insufficient selectivity within the 3 kinases. The compound shows in vivo efficacy. Tumor growth dose response has been measured at 5 concentrations. A correlation between plasma concentration versus PD effect has been measured. Structure alert: desmotropie isomerism, the compound can be drawn in different versions.

(last updated: 22 Mar 2023 )