JAK-2-/3-IN-3 (compound ST4j) is a potent inhibitor of JAK2/3, with IC50 values of 13.00 and 14.86 nM for JAK2 and JAK3, respectively. It inhibits JAK2 autophosphorylation, induces apoptosis in a time- and dose-dependent manner, and can be used in lymph-derived diseases and leukemia research [1].

JAK2:13.00 nM, JAK3:14.86 nM

JAK-2/3-IN-3, within a concentration range of 0-100 µM over 72 hours, selectively targets human erythroleukemia cells, demonstrating minimal toxicity towards normal cells. It exerts its effect primarily through inhibiting the JAK2/STAT5 signaling pathway, crucial for the proliferation of erythroleukemia TF1 cell line. Additionally, exposure to 15.53 µM of JAK-2/3-IN-3 induces apoptosis in a time-dependent manner within TF1 cells, culminating in increased apoptotic rates of approximately 20%, 40%, and 70% after 24, 48, and 72 hours, respectively. Further dose-dependent investigations reveal escalating apoptosis within TF1 cells at concentrations corresponding to IC 25, IC 50, and IC 75 over a 24-hour period, with noted apoptotic increases of approximately 15%, 20%, and 30%. In cell cytotoxicity assays involving TF1, HEL, Vero, and HepG2 cells treated with up to 100 µM of JAK-2/3-IN-3 for 72 hours, the compound demonstrated inhibition of TF1 and HEL cell growth with IC 50 values of 15.53 and 17.90 µM, respectively, while proving less toxic to normal Vero and HepG2 cells, with IC 50 values exceeding 100 µM for Vero cells and 50 µM for HepG2 cells.