FIIN-1

FIIN-1 : Covalent inhibitor of FGFR1, FGFR2, FGFR3, FGFR4

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

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Probe FIIN-1 is in the process of SERP review.

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Information

FGFR1
FGFR2
FGFR3
FGFR4

Covalent Inhibitor

up to 200 nM

Probe Availability:

MCULE

In Vitro Validations

Uniprot ID: P11362

Target Class: Kinase

Target SubClass: Tyrosine kinase

Potency: Kd

Potency Value: 2.8 nM

Potency Assay: Biochemical Assay

PDB ID for probe-target interaction (3D structure): 6C1O

Target aliases:

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

DOI Reference: 10.1016/j.chembiol.2010.02.007

Uniprot ID: P11362

Target Class: Kinase

Target SubClass: Tyrosine kinase

Potency: IC50

Potency Value: 9.2 nM

Potency Assay: Z′-lyte assay

PDB ID for probe-target interaction (3D structure): 6C1O

Target aliases:

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

DOI Reference: 10.1016/j.chembiol.2010.02.007

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): FIIN-1 and FRIN-1 were profiled against a panel of 402 different kinase binding assays using the Ambit KinomeScan technology at a concentration of 10 μM. Only two other kinases associated with FIIN-1 with KD's below 100 nM were Blk (KD = 65 nM) and Flt1 (KD = 32 nM).

Potency assay, off target (cells): FIIN-1 was profiled using a panel of various tyrosine kinase-transformed Ba/F3 cells. FIIN-1 was not cytotoxic toward wild-type (WT) Ba/F3 cells (EC50 > 10 μM) and was barely active against Bcr-Abl (EC50 > 10 μM), NPM-Alk (EC50 > 10 μM), Tpr-Met (EC50 > 10 μM), Tel-Arg (EC50 > 10 μM), Tel-Blk (EC50 = 2 μM), Tel-Bmx (EC50 = 2 μM), Tel-Jak2 (EC50 = 5 μM), and Tel-Jak3 (EC50 > 10 μM). The observed low activity against Tel-Blk, Bmx, and Jak3, which contain a reactive cysteine in the ribose binding region further confirms selectivity of FIIN-1.

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SERP ratings and comments

SERP+ Ratings

In Cell Rating

SERP+ Comments:

FIIN1 is a very potent covalent inhibitor for FGFR1 and FGFR3 with IC50 values below 15 nM (in vitro). Convincing proof of covalent binding mode by pharmacological and genetic controls. Selectivity of the compound was shown by kinome wide screening (402 kinases) at 10 uM with only BIK and Flt1 as off targets with IC50 values of 381 nM and 661 nM. Proteome-wide selectivity is missing No cytotoxicity toward wild-type (WT) Ba/F3 cells. Multiple compounds are approved as probe in the Portal for the FGFR family with higher potency. FIIN1 is the first covalent inhibitor for the FGFR family and inhibits the V561M gatekeeper mutation in FGFR1. The probe is rather to be highlighted as a V561M mutated FGFR1 probe than as probe for the whole FGFR family by the fact that there are more potent and better characterised probes already accepted in the Portal.

(last updated: 23 Sept 2024 )