Sovleplenib (HMPL523) is an orally available, selective and potent inhibitor of the splenic tyrosine kinase SYK with an IC50 of 25 nM.Sovleplenib has antitumor activity and may be used in studies of immune thrombocytopenia (ITP).

Syk:25 nM

Sovleplenib (HMPL-523) exhibits inhibitory activity with IC50 values of 0.025 μM, 0.063 μM, 0.390 μM, 0.921 μM, 3.214 μM, and 3.969 μM against SYK, FLT3, KDR, LYN, FGFR2, and AUR A, respectively.[2]
Sovleplenib effectively blocks the phosphorylation of BLNK, a downstream protein of Syk, in human mantle cell line REC-1 and human plasma cell line ARH-7777, with IC50 values of 0.105 μM and 0.173 μM, respectively.[2]
Sovleplenib also significantly reduces cell viability in Ba/F3 Tel-Syk cells with an IC50 of 0.033 μM and increases the rate of apoptosis in REC-1 cells.[2]
Sovleplenib demonstrates synergistic effects in combination with other drugs, including BTK inhibitors, PI3Kδ inhibitors, and Bcl2 family inhibitors, in killing human-diffuse large B cell lymphoma (DLBCL).[2]

Sovleplenib (HMPL-523) (10 and 100 mg/kg; once daily for 8 days; Balb/c nude mice with subcutaneously implanted REC-1 cells or intravenously injected BA/F3 cells or BA/F3 TEL-SYK cells) Inhibited tumor growth in REC-1 subcutaneous xenograft model at 100 mg/kg.[1]
Sovleplenib (HMPL-523; 100 mg/kg; daily oral administration; for 8 days) shows potent anti-tumor activity in B cell lymphoma REC-1 (TGI: 59%) in Syk-dependent xenograft models.[2]