Bafetinib

Inhibitor of ABL1, LYN

Structure

Information

Protein target names: ABL1, LYN

Mechanism of action: Inhibitor

In Vitro Validations

Uniprot ID: P00519
Target Class: Kinase
Target SubClass: TK
Potency: IC 50
Potency Value: 5.8 nM
Potency Assay: Kinase Profiler
PDB ID for probe-target interaction (3D structure): 2E2B
Target aliases:
Tyrosine-protein kinase ABL1, JTK7, ABL, ABL1, ABL ...

DOI Reference: 10.1182/blood-2005-06-2209

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

If using bafetinib (INNO-406) as a probe, it is highly recommended to consult the publication by U. Rix et al (Leukemia 2010, 24, 44–50). They've exhaustively profiled it through unbiased chemical proteomics and biochemical assays to better understand the selectivity profile. Notably, some known off-targets of imatinib and nilotinib were not present (NQO2) in the profile and the pattern of other kinases inhibited were different.

Another point to consider is the favorable CNS activity in comparison to imatinib (Yokota et al, Blood 2007, 109:306-314).

(last updated: 12 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

This probe is similar to imatinib and was designed to inhibit mutant ABL kinases that are resistant to imatinib. This probe was intended to inhibit LYN kinase. Overexpression of LYN is usually associated with imatinib resistance. Bafetinib inhibits four tyrosine kinases >50%: ABL, ABL-related gene (ARG), FYN, and LYN at 100 nM in vitro. The IC50 for ABL is 5.8 nM, and for LYN is 19 nM. It is more selective than imatinib and does not inhibit PDGFR or c-KIT kinases in vitro, which are inhibited by imatinib. Bafetinib inhibits clinically resistant ABL mutants (in vitro IC50 ranges 72 nM to 760nM). This probe does not inhibit T315I mutant ABL. Bafetinib inhibits tumor growth in vivo in mice that were subcutaneously injected with BCR-ABL positive KU812 cells, followed by oral administration of 200 mg/kg/day bafetinibat.

(last updated: 14 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

There are better compounds to study ABL in cells and animal models (e.g., GNF-2 and GNF-5). I do not recommend using bafetinib as a probe for ABL.

(last updated: 16 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Bafetinib is a more selective probe compound than imatinib (see Kimura, S. et al, Blood, 2005, 106, 3948-3954) based on cellular and non-cellular kinase inhibition selectivity data. Additionally, bafetinib has a superior in vitro kinase inhibition profile against BCR-ABL variants with point mutations in the kinase domain. The above reference details cellular selectivity only against relatively small panels of kinases in cellular and in vitro kinase assays.

(last updated: 6 Jul 2016 )