HR-19011

HR-19011 is an eIF2α phosphorylation activator targeting heme-regulated inhibitor HRI (EIF2AK1). HR-19011 exhibits growth inhibitory activity against K562 cells with an IC₅₀ value of 3.91 µM. HR-19011 inhibits the growth of hematologic malignancies by targeting HRI to activate the integrated stress response via the HRI-eIF2α-ATF4 axis. HR-19011 shows good safety in vivo. HR-19011 can be used for research on hematologic malignancies (leukemia)^[1][2]. In Vitro:HR-19011 (compound 40) (1.25-20 μM, 72 h) shows an anticancer activity with IC₅₀ values of 4 and 19.3 μM in K562 and human peripheral blood mononuclear cells (PBMC) cell, shows a strong cancer cell selectivity with a SI value of 4.83 in PBMC cells^[1].
HR-19011 (0-10 μM, 24 h) activate eIF2α phosphorylation in an eIF2α/ATF4/CHOP pathway-dependent manner in K562 cells^[1].
HR9011 exhibits cell growth inhibitory activity with an IC₅₀ value of 3.91 µM in K562 cells transfected with nontargeting control shRNA, while the IC₅₀ value increases to 8.03 µM in K562 cells stably transfected with HRI-specific shRNA^[1].
In Vivo:HR9011 (i.p., one week) demonstrates good safety n Balb/c mice, with no significant tissue damage, body weight loss, or mortality observed and exhibits significant antitumor activity in tumor-inducing mouse models ^[2].