LLL3

LLL3 (CLT-005) is an orally effective STAT3 inhibitor. LLL3 blocks STAT3 dimerization, nuclear translocation, and transcription by binding to the SH2 domain. LLL3 induces apoptosis and PARP/caspase-3 cleavage, thereby inhibiting the proliferation and invasion of cancer cells. LLL3 reduces retinal vascular permeability, pro-angiogenic and pro-inflammatory factor levels, ameliorates diabetes-related vision loss and cataracts, and exhibits good biosafety. LLL3 inhibits tumor growth in vivo. LLL3 can be used in research related to glioblastoma, breast cancer, chronic myeloid leukemia, and diabetic retinopathy^[1][2][3]. In Vitro:LLL3 (20 μM; 48 h) inhibits STAT3-dependent transcription in MDA-MB-231 breast cancer cells^[1].
LLL3 (20-50 μM; 48 h) inhibits STAT3-specific DNA binding in U373 glioblastoma and MDA-MB-231 breast cancer cells^[1].
LLL3 (10-40 μM; 72 h) reduces the viability of U87, U251, and U373 glioblastoma cells^[1].
LLL3 (8-200 μM; 24-48 h) inhibits K562 cell viability in a dose- and time-dependent manner^[2].
LLL3 (5-20 μM; 24 h) inhibits DU145 cell viability with an IC₅₀ of 11.3 μM^[2].
LLL3 (5-80 μM; 24 h) inhibits MCF-7 cell viability only at high concentrations, with an IC₅₀ of 150 μM^[2].
LLL3 (40 μM; 24-48 h) combined with Imatinib Mesylate (HY-50946) increases the mortality of K562 cells by 21%-22% compared with Imatinib Mesylate alone^[2].
LLL3 (40 μM; 24 h) increases sub-G1 DNA content in K562 cells and enhances IM-induced increases in sub-G1 DNA^[2].
LLL3 (40 μM; 24 h) induces apoptosis in K562 cells^[2].
LLL3 (40 μM) activates Caspase-3/7 in K562 cells and enhances IM-induced Caspase-3/7 activation^[2].
LLL3 (20 μM; 48 h) induces caspase-3 cleavage in U87 and U373 glioblastoma cells, but not in normal human bladder smooth muscle cells^[1].
LLL3 (20 μM; 48 h) induces PARP cleavage in U87, U251, and U373 glioblastoma cells^[1]. In Vivo:LLL3 (50 mg/kg; intratumoral injection; single injection) reduces intracranial tumor volume and prolongs median survival in nude mice bearing U87 glioblastoma xenografts^[1].
LLL3 (50 ng/eye-5 µg/eye; intravitreal injection; single injection) reduces retinal vascular permeability and pro-angiogenic/pro-inflammatory mRNA expression in Streptozotocin (HY-13753)-induced diabetic Brown Norway rats^[3].
LLL3 (125-500 mg/kg/animal; p.o.; once daily; administered continuously for 16 weeks starting 3 days after Streptozotocin injection) delays diabetes-induced vision loss and reduces retinal phosphorylated Stat3 and inflammatory cytokine levels in Streptozotocin-induced diabetic Brown Norway rats^[3].