Fig. 2.

Timeline of the historical milestone for the discovery of protein phosphatases and their crucial inhibitors. SHP099 and TNO155 are SHP2 allosteric inhibitors. ISIS-113715 and MSI-1436 are PTP1B inhibitors. LB-100 is a PP2A inhibitor. PRL3-zumab is a monoclonal antibody of PRL3. The discovery of all the protein phosphatases take a long time and we show the time point for the first identified or cloned of all the protein phosphatases involved in the inflammation-related diseases (PP2A,²² DUSP1,³³⁸ CD45,³³⁹ PTP1B,²³⁵ PTPN2,³⁴⁰ PP1,²³ SHP1,³⁴¹ SHP2,²³⁸ DUSP2,³⁴² PP4,²⁶ PRL-1,³⁴³ PTPN14,³⁴⁴ DUSP5,³⁴⁵ DUSP6,³⁴⁶ PP6,²⁷ PP2C,¹⁷ PRL-2/3,³⁴⁷ PTPN22,³⁴⁸ DUSP10,³⁴⁹ DUSP14,³⁵⁰ DUSP22,³⁵¹ and DUSP26³⁵²) and the generation and development of their inhibitors in clinical trials (PRL3-zumb,²⁴¹ LB-100²⁴², ISIS113715,²³⁶ MSI-1436,²³⁷ and TNO155.²⁴⁰) SHP099 is the first allosteric inhibitor of SHP2 found by Novartis in 2016, which is a breakthrough in the study of allosteric inhibitor in the field of designing compound targeting protein phosphatases²³⁹