Roblitinib

Roblitinib : Reversible-Covalent Inhibitor of FGFR4

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe Roblitinib is in the process of SERP review.

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Information

FGFR4

Reversible

up to 100 nM

Probe Availability:

In Vitro Validations

Uniprot ID: P22455

Target Class: Kinase

Target SubClass: TK

Potency: IC50

Potency Value: 0.9 ± 0.4 nM

Potency Assay: Biochemical Assay

PDB ID for probe-target interaction (3D structure): 6YI8

Structure-activity relationship: yes

Target aliases:

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

DOI Reference: 10.1021/acs.jmedchem.0c01019

Uniprot ID: P22455

Target Class: Kinase

Target SubClass: TK

Potency: Kd

Potency Value: 2.9 nM

Potency Assay: Biochemical Assay

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

Target aliases:

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

DOI Reference: 10.1021/acs.jmedchem.0c01019

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): KINOMEscan

Probe Selectivity in Vitro:

1000-fold selectivity for FGFR4 compared to the next most potent kinase inhibited (Aurora A: IC50 5.6 μM), including no appreciable activity in both biochemical and cellular assays versus the other FGFR family members (@ 10 μM). A KINOMEscan with Roblitinib showed <35% displacement of the reporter binding against the whole panel of 456 off-target kinases @ 3 μM. Of the other GK+2 cysteine containing kinases, only MAPKAPK2 (MK2) showed any appreciable inhibition (biochemical IC50 = 9.4 μM) Outside target family: In enzyme and receptor screens, Roblitinib exhibited no appreciable activity at a concentration of 10 μM against 138 representative off-targets.

Potency assay (off target): Enzyme and Receptor screens

Probe Selectivity in Vitro:

In enzyme and receptor screens, 84 exhibited no appreciable activity at a concentration of 10 μM against 138 representative off-targets.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

This is an exquisitely selective probe for FGFR4 (specific to this isoform within the FGFR family) with significant target validation and selectivity profiling across kinases and other targets, showing no noticeable off target activity at the recommended concentrations. Activity was also validated in vivo and the compound is currently under investigation in clinical trials

(last updated: 8 Nov 2024 )