Epibestatin hydrochloride is an epimer of Bestatin, a DPP4 inhibitor and protease inhibitor, with an IC50 of 17 μM against DPP4. As a stabilizer, Epibestatin hydrochloride binds to the cleft between 14-3-3 protein and plant proton pump PMA2, selectively stabilizing their interaction without affecting other 14-3-3 client proteins. Epibestatin hydrochloride triggers stomatal opening in leaf epidermis of Commelina communis. Epibestatin hydrochloride can be used in studies related to type 2 diabetes [1] [2] [3].
In Vitro, Epibestatin (0.5-50 μM; 90 min) hydrochloride inhibits purified dipeptidyl peptidase 4 (DPP4) with an IC50 of 17 μM, showing dose-dependent inhibitory activity across concentrations from 0.5 to 50 μM, while its epimer bestatin shows no DPP4 inhibitory activity[1]. Epibestatin (50 μM) hydrochloride stabilizes the interaction between purified 14-3-3 protein and PMA2-CT52 with a KD of 1.8 μM, as measured via surface plasmon resonance[3]. Epibestatin (50 μM; 3 h) hydrochloride induces stomatal opening in isolated Commelina communis leaf epidermis to an average width of 3.2 μm after 3 hours of incubation[3]. Epibestatin hydrochloride does not stabilize the interaction between purified 14-3-3 protein and any of the tested alternative targets (Raf1, p53, Cdc25C, RNF11, Mlf1, AICD, Cby, YAP), demonstrating selectivity for the 14-3-3/PMA2 complex[3].
References:
[1]. Kawaguchi M, et al. A time-resolved fluorescence probe for dipeptidyl peptidase 4 and its application in inhibitor screening. Chemistry (Weinheim an der Bergstrasse, Germany). 2010 Dec 03;16(45):13479-86.
[2]. Richter A, et al. A practical and convenient synthesis of the protease inhibitor epibestatin[J]. Synthesis, 2010, 2010(12): 2039-2042.
[3]. Rose R, et al. Identification and structure of small-molecule stabilizers of 14-3-3 protein-protein interactions. Angew Chem Int Ed Engl. 2010 Jun 1;49(24):4129-32.
In Vitro, Epibestatin (0.5-50 μM; 90 min) hydrochloride inhibits purified dipeptidyl peptidase 4 (DPP4) with an IC50 of 17 μM, showing dose-dependent inhibitory activity across concentrations from 0.5 to 50 μM, while its epimer bestatin shows no DPP4 inhibitory activity[1]. Epibestatin (50 μM) hydrochloride stabilizes the interaction between purified 14-3-3 protein and PMA2-CT52 with a KD of 1.8 μM, as measured via surface plasmon resonance[3]. Epibestatin (50 μM; 3 h) hydrochloride induces stomatal opening in isolated Commelina communis leaf epidermis to an average width of 3.2 μm after 3 hours of incubation[3]. Epibestatin hydrochloride does not stabilize the interaction between purified 14-3-3 protein and any of the tested alternative targets (Raf1, p53, Cdc25C, RNF11, Mlf1, AICD, Cby, YAP), demonstrating selectivity for the 14-3-3/PMA2 complex[3].
References:
[1]. Kawaguchi M, et al. A time-resolved fluorescence probe for dipeptidyl peptidase 4 and its application in inhibitor screening. Chemistry (Weinheim an der Bergstrasse, Germany). 2010 Dec 03;16(45):13479-86.
[2]. Richter A, et al. A practical and convenient synthesis of the protease inhibitor epibestatin[J]. Synthesis, 2010, 2010(12): 2039-2042.
[3]. Rose R, et al. Identification and structure of small-molecule stabilizers of 14-3-3 protein-protein interactions. Angew Chem Int Ed Engl. 2010 Jun 1;49(24):4129-32.