BTdCPU

BTdCPU (1-(benzo[d][1,2,3]thiadiazol-6-yl)-3-(3,4-dichlorophenyl)urea) is a small molecule activator of eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1), also known as heme-regulated inhibitor (HRI) kinase. By activating HRI, BTdCPU promotes the phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α), triggering the integrated stress response (ISR) pathway. This leads to global translation attenuation and selective upregulation of stress-responsive transcription factors such as ATF4 and CHOP. BTdCPU has been extensively studied in preclinical models of hematological malignancies, including multiple myeloma and acute lymphoblastic leukemia, where it induces apoptosis and overcomes resistance to dexamethasone and proteasome inhibitors like bortezomib. Additionally, BTdCPU has demonstrated neuroprotective efficacy in preclinical models of ischemic stroke, where it reduces lesion and edema volumes and improves behavioral recovery, particularly when combined with recombinant tissue plasminogen activator (rtPA).

Other names

1-(1,2,3-benzothiadiazol-6-yl)-3-(3,4-dichlorophenyl)urea1-(benzo[d][1,2,3]thiadiazol-6-yl)-3-(3,4-dichlorophenyl)ureaN-(benzo[d][1,2,3]thiadiazol-6-yl)-N'-(3,4-dichlorophenyl)urea