PTPN22-IN-1, detailed in WO2021007491A1 as compound L-1, is a potent PTPN22 inhibitor, demonstrating an IC50 of 1.4 μM and a Ki of 0.50 μM. This compound achieves over 7-10 fold selectivity against PTPN22 relative to comparable phosphatases and enhances antitumor immune responses.

PTPN22-IN-1, also referred to as Compound L-1, demonstrates noteworthy anti-tumor properties when administered intraperitoneally to wild-type (WT) mice, significantly attenuating MC38 tumor growth. Similarly, in a syngeneic immunocompetent model using CT26 in Balb/c mice, PTPN22-IN-1 exhibits comparable anti-tumor effects. The intraperitoneal administration of L-1 at a dosage of 10 mg/kg results in an average area under the curve (AUC) of 4.55 μM h and a maximum concentration (C max) of 1.11 μM, as depicted in Figure 9d. Notably, the observed C max is more than double its inhibitory constant (K i) value, underscoring the compound's potent efficacy[1].

PTPN22-IN-1 (Compound L-1) (WT mice; intraperitoneally) significantly reduces MC38 tumor growth. PTPN22-IN-1 (syngeneic immunocompetent model; CT26 in Balb/c mice) shows similar antitumor effects[1]. Administration of L-l intraperitoneally at 10 mg/kg yielded an average AUC of 4.55 μM h and C max of 1.1 1 μM (Fig. 9d), which is more than twice of its K i value[1].