BI-0319

BI-0319 : Degrader (PROTAC) of PTK2

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

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Probe BI-0319 is in the process of SERP review.

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Information

PTK2

Degrader (PROTAC)

up to 1 uM, hook effect in the A549 cells at 25 μM

In Vitro Validations

Uniprot ID: Q05397

Target Class: Kinase

Target SubClass: Tyr kinase

Potency: IC50

Potency Value: 19 nM

Potency Assay: Thermo Fisher SelectScreen Kinase Profiling

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

Target aliases:

Focal adhesion kinase 1, FAK1, FAK, PTK2, FAK1_HUM ...

DOI Reference: 10.1021/acs.jmedchem.8b01826

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): In a 397 kinase kinase panel BI-0319 beside PTK2 only inhibited LRRK2 and FES by more than 50% at 1 µM.

Potency assay, off target (cells): Multiplexed isobaric tagging mass spectrometry was employed to assess the cellular selectivity of BI-0319 for PTK2 degradation and identify potential degradation off-targets in a quantitative and unbiased manner. Amongst the 6,008 proteins quantified in this analysis in A549 cells, PTK2 showed a distinct and significant change in abundance upon treatment with BI-0319. BI-0319 did not induce any significant changes in abundance of other detectable kinases, thus confirming the high selectivity of both degraders within the kinase family. Of note, the two most prominent kinase off-targets of the inhibitor (LRRK2 and FES) were not detected in this dataset.

Potency assay, off target (cells): BI-0319 degradation of PTK2 was assessed in a panel of 11 HCC cell lines.

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SERP ratings and comments

SERP+ Ratings

In Cell Rating

SERP+ Comments:

BI-0319 is a selective PROTAC degrader of PTK2, with three main off-targets (LRKK2, FES, and PDE60) identified by either a kinase panel or unbiased proteomics. In several human hepatocellular carcinoma (HCC) cell lines, it demonstrates a pDC50 > 7 and in A549 cells a Dmax of 80%. Dmax is achieved at 20 h in Hep3B2.1-7 cells; however, the achieved Dmax in this cell line is only 60%. NEDDylation inhibitors and a negative control PROTAC (BI-4206 - E3 ligase binder enantiomer) ablated degradation. No direct evidence of cell TE (e.g. nanoBRET on POI, POI binder negative control); however, POI binder with linker inhibits PTK2 in-vitro. No evidence of ternary complex formation. Evidence of Hook effect at 25 uM is weak in A549 cells but would recommend usage up to 1 uM.

(last updated: 6 Feb 2026 )