Eya2 Phosphatase Inhibitor, MLS000544460

A cell-permeable furylidenebenzohydrazide compound that acts as a reversible inhibitor against Eya2 C-terminal Eya domain (ED) protein tyrosine phosphatase (PTP) activity (IC₅₀ = 4.1 µM; 100 nM ED & 5 µM Mg²⁺; Substrate = 25 µM OMFP) via affinity docking at an allosteric pocket located opposite to the active site (K_D = 6.1 or 2.0 µM, respectively, with or without 5 mM exogenous Mg²⁺; K_D = 0.8 µM with 10 mM EDTA and no exogenous Mg²⁺), while being ineffective against the PTP activity of Eya3 & PTP1B or the Ser/Thr phosphatase activity of PPM1A & Scp1. Shown to reduce Eya2 overexpression-induced migration enhancement in MCF10A cultures (17% vs. 54% enhancement with or without 10 µM inhibitor). The inhibition appears to be non-competitive with respect to substrate in the presence of 5 mM Mg²⁺, while mixed mode of inhibition is observed at a low Mg²⁺ concentration of 5 µM.

A cell-permeable furylidenebenzohydrazide compound that acts as an inhibitor of Eya2 ED tyrosine phosphatase (IC₅₀ = 4.1 µM; K_D = 2.0 µM for hEya2, catalytic domain at 5 µM Mg²⁺). Inhibition appears to be reversible and allosteric in nature. Does not affect the activity of Eya3, PTP1B, PPM1A, and Scp1 even at higher concentration (IC₅₀ >100 µM). Although its binding to Eya2 ED is not Mg²⁺ dependent, its inhibitory activity is dependent on the concentration of Mg²⁺ in the medium. At higher Mg²⁺ levels (~5 mM) the inhibition is non-competitive whereas at low Mg²⁺ levels (~5 µM) it has a mixed type inhibition. Reduces Eya2-mediated cell migration in MCF10A cells (~ 10 µM).

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Cell permeable: yes

Primary Target
Eya2 C-terminal Eya domain (ED) protein tyrosine phosphatase

Reversible: yes

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Krueger, A.B., et al. 2014. J. Biol. Chem.289, 16349.

Krueger, A.B., et al. 2013. J. Biomol. Screen.18, 85.

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