The dysfunction in the SHP1 can cause cancers and many diseases, so it is of great significance to develop novel small molecule SHP1 inhibitors. Through continuous monitoring of metabolic and targeted processes of SHP1 inhibitors in real-time, we can evaluate the effectiveness and toxicity of inhibitors, optimize drug design, and explore SHP1 biology information. Indoloquinoxaline is an important class of N-containing heterocyclic compounds, which is studied and applied in various pharmacological activities and optoelectronic materials. In this work, the potential visual src homology 2 domain-containing phosphatase 1 (SHP1) inhibitors 5a was developed with the help of structural fusion and scaffold hop of fluorophore 6H-indolo-[2,3-b]-quinoxaline and bio-active skeleton thieno[2,3-b]quinoline-procaine. The representative compound 5a selectively inhibited the SHP1PTP enzyme abilities (IC50 = 2.34 ± 0.06 μM), had a significant fluorescence response (P = 0.007) against SHP1PTP activity, and emitted strong blue and green fluorescence in MDA-MB-231 cells. What’s more, the compound 5a showed irreversible binding property with the SHP1PTP by simulation and dialysis experiments. Thus, compound 5a serves a dual purpose, combining imaging and therapeutic functionalities, enhancing our understanding of SHP1 biological mechanisms, and positively impacting novel drug development.

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