FGFR4-IN-8B

FGFR4-IN-8B : Covalent Inhibitor of FGFR4

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe FGFR4-IN-8B is in the process of SERP review.

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Information

FGFR4

Covalent Inhibitor

up to 1 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: P22455

Target Class: Kinase

Target SubClass: Tyrosine kinase

Potency: IC50

Potency Value: 0.5 nM

Potency Assay: HotSpot assay at a 10 μM ATP concentration

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

Target aliases:

Fibroblast growth factor receptor 4, TKF, JTK2, FG ...

DOI Reference: 10.1021/acs.jmedchem.3c02483

Uniprot ID: P22455

Target Class: Kinase

Target SubClass: Tyrosine kinase

Potency: Ki

Potency Value: 5.7 ± 0.17 nM

Potency Assay: PhosphoSens CSox-based continuous assay kinact/Ki 2.32 × 10^5 (M–1·s–1)

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

Target aliases:

Fibroblast growth factor receptor 4, TKF, JTK2, FG ...

DOI Reference: 10.1021/acs.jmedchem.3c02483

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): 8B was tested in the HotSpot format against all other FGFRs as well as MAPKAPK2, MAPKAPK3, S6K2, and TTK harboring a GK+2 cysteine. 8B was highly selective within the FGFR family with compound 8B showing weak inhibitory activity for FGFR1 (IC50 = 4.4 μM) and FGFR2 (IC50 = 490 nM), while all other IC50 values were above 5 μM. 8B was further assessed against 104 kinases with a broad distribution in the kinome using a differential scanning fluorimetry-based assay (thermal shift assay).

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SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 24 Jun 2024 )

SERP Ratings

In Cell Rating

SERP Comments:

FGFR4-IN-8B is a covalent inhibitor of FGFR4 kinase with minimal activity over FGFR1-3 isoforms that lack the reactive cysteine that the compound targets. Based on two separate kinome-screening methods, FGFR4-IN-8B has very good kinase selectivity. A FGFR NanoBRET assay indicated high isoform selectivity in mammalian cells and potent antiproliferative activity in Hep3B cells further suggest robust target engagement. Liver microsome assays indicate that the compound is metabolically relatively stable, but in vivo activity is not tested. In conclusion, FGFR4-IN-8B is a highly isoform-selective covalent FGFR4 inhibitor suitable for cellular experiments. A nonreactive control compound, cpd14A, is reported with minimal activity against FGFR4.

(last updated: 8 Jul 2024 )