UNC2025

UNC2025 : ATP-competitive inhibitor of FLT3, MERTK

Structure

Information

Protein target names: FLT3, MERTK

Mechanism of action: ATP-competitive inhibitor

Recommended in-cell concentration:
1-20 nM
Primary References:

In Vitro Validations

Uniprot ID: P36888
Target Class: Kinase
Target SubClass: TK
Potency: IC 50
Potency Value: 0.8 nM
Potency Assay: Microcapillary assay (Carna Biosciences)
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: Yes, see J Med Chem paper
Target aliases:
Receptor-type tyrosine-protein kinase FLT3, STK1, ...

DOI Reference: 10.1021/jm500749d

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

UNC2025 is a dual inhibitor of MER and FLT3 tyrosine kinases with a subnanomolar potency in a cell-free kinase assay (0.74 nM for MER and 0.80 nM for FLT3) and a low nanomolar-range potency in cell-based pharmacodynamic (PD) assays (2.7 nM for MER and 14 nM for FLT3). The compound showed significant selectivity for MER and FLT3 over other related as well as unrelated kinases with in the kinome tree. In addtion, the compound possesses good enough pharmacokinetic and PD profiles for in vivo experiments. These data suggest that UNC2025 is suitable as a chemical probe in cellular models as well as mouse disease models.     

(last updated: 17 Apr 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

UNC2025 is a dual inhibitor of MER and FLT3. In practice, it will not be feasible to distinguish MER from FLT3 effects for analyzing downstream pathways, although there seems several-fold difference in the impact of the compound on these kinase targets in cellular models.

(last updated: 27 Apr 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

UNC2025 is a very well characterized, dual inhibitor of MER and FLT3 kinases with subnanomolar potency in vitro and low nanomolar potency in cells (2.7 nM for MER and 14 nM for FLT3). In this range, the compound is highly selective over other kinases, but care must be taken not to over dose the compound and stay in the recommended range. The compound also shows sufficient activity to be used in mouse models.

(last updated: 16 May 2017 )

SERP Comments:

UNC2025 is a potent dual FLT3/MER inhibitor. This compound did, however, inhibit 66 kinases below 50% of control in a biochemical assay at 100 nM. The top 10 targets are reported with all having IC50's below 10 nM so using an appropriate concentration of the compound is important in experiments. The data suggests that UNC2025 is also suitable for use in mouse models.

(last updated: 17 May 2017 )