ATX inhibitor 13

ATX inhibitor 13 (10c) is an orally active and potent ATX inhibitor, with an IC50 of 3.4 nM. ATX inhibitor 13 inhibits proliferation and migration, and induces apoptosis and G2 phase arrest in RAW264.7 cells. ATX inhibitor 13 suppresses tumor cell colony formation[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

ATX:3.4 nM (IC50)

ATX inhibitor 13 (compound 10c) (0-20 μM, 72 h) shows cytotoxicity and anti-proliferative activity against MCF-7, MDA-MB-231, A549, NCI-H1581, H2228, Hep3B, and RAW264.7 cells[1]. ATX inhibitor 13 (0-1 μM, 0-72 h) inhibits migration of RAW264.7 cells in a dose-dependent manner, significantly down-regulates both the colony count and colony single area with the concentration elevation[1]. ATX inhibitor 13 (0-1 μM, 72 h) dose dependently suppresses colony formation of RAW264.7 cells[1]. ATX inhibitor 13 (0-1 μM, 48 h) induces weak apoptosis in a dose-dependent manner in RAW264.7 cells[1]. ATX inhibitor 13 (0-1 μM, 48 h) brings G2 phase arrest of RAW264.7 cells[1]. Cell Proliferation Assay Cell Line: MCF-7, MDA-MB-231, A549, NCI-H1581, H2228, Hep3B, RAW264.7[1] Concentration: 0-20 μM Incubation Time: 72 h Result: Showed cytotoxicity and antiproliferative activity against MCF-7, MDA-MB-231, A549, NCI-H1581, H2228, Hep3B, and RAW264.7 cell lines, with IC50 values of 3.87 ± 0.37, 3.29 ± 0.37, 6.59 ± 0.26, 4.76 ± 0.57, 4.27 ± 0.21, 0.58 ± 0.11, and 0.63 ± 0.26 μM. Apoptosis Analysis Cell Line: RAW264.7 cells[1] Concentration: 0 μM, 0.1 μM, 0.25 μM, 0.5 μM and 1 μM Incubation Time: 48 h Result: Induced apoptosis in a dose-dependent manner, with the apoptotic rates of 6.48% (0.1 μM), 7.73% (0.25 μM), 8.60% (0.5 μM) and 9.17% (1 μM). Cell Cycle Analysis Cell Line: RAW264.7 cells[1] Concentration: 0 μM, 0.1 μM, 0.25 μM, 0.5 μM and 1 μM Incubation Time: 24 h Result: Led to significant G2 phase arrest in RAW264.7 cells in a dose-dependent manner, the percentage of cells in the G2 phase slightly increased from 10.90% to 90.16% (0-1 μM).

ATX inhibitor 13 (compound 10c) (C57BL/6J mice, 0-1000 mg/kg, Orally, once) has an acceptable safety profile[1]. Animal Model: C57BL/6J mice (5 groups,4 mice per group)[1] Dosage: 5000, 3200, 2500 and 1000 mg/kg Administration: Orally, once Result: Had an acceptable safety profile, showed no obvious safety concerns.

[1]. Lei H, et al. Design, synthesis and promising anti-tumor efficacy of novel imidazo[1,2-a]pyridine derivatives as potent autotaxin allosteric inhibitors. Eur J Med Chem. 2022;236:114307.