| Description |
EB-3D is a novel potent and selective choline kinase ChoKα inhibitor with IC50 of 1.0 uM (purified ChoKα1), strongly impairs cell proliferation in a variety of different cancer cell lines; demonstrates in vitro antiproliferative effects against HeLa (IC50=79 nM), RS4,11 (IC50=45 nM), A549 (IC50=27 nM) and MDA-MB-231 (IC50=100 nM); displays excellent antiproliferative activity against a wide cohort of T-leukemic cell lines with GI50 of 0.9 nM (MOLT-16 cell)-479 nM (CCRF-CEM), reduces the intracellular pool of PCho, but also inhibits the synthesis of choline-containing lipids; induces G0/G1 arrest that lead to apoptosis in leukemia cell lines; affects AMPK-mTOR signaling pathway, synergizes with both dexamethasone and L-asparaginase.
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| In Vitro |
EB-3D displays (0-100 μM; 72 hours) excellent antiproliferative activity against a wide cohort of T-leukemic cell lines, with GI GI50s 13 values in the nanomolar range[1]. EB-3D (1.25-5μM; 24 hours) induced apoptosis in leukemia cell lines[1]. EB-3D (0.5-1 μM; 24 hours) induces a G0/G1 arrest that lead to apoptosis[1]. EB-3D (0.3 μM; 48 hours) shows a first spike of activation of AMPKα after 30 minutes and a later increase in the phosphorylation of T172[1]. EB-3D (1-40 μM; 48 hours) inhibits cell growth in HepG2 cells with a GI50 of 14.55 μM[2]. Cell Proliferation Assay[1] Cell Line: JURKAT, CCRF-CEM, HSB-2, MOLT-16, DNA-41, LOUCY, PEER, ALL-SIL cells Concentration: 0.001, 0.01, 0.1, 1, 10, 100 μM Incubation Time: 72 hours Result: Inhibited JURKAT, CCRF-CEM, HSB-2, MOLT-16, DNA-41, LOUCY, PEER, and ALL-SIL cells growth with GI50s of 136.2, 478.8, 17.7, 0.9, 60.6, 200, 265, and 132 nM, respectively. Apoptosis Analysis[1] Cell Line: Jurkat, CCRF-CEM and HSB-2 cells Concentration: 1.25, 2.5, 5 μM Incubation Time: 24 hours Result: Induced apoptosis in leukemia cell lines. Cell Cycle Analysis[1] Cell Line: Jurkat, CCRF-CEM and HSB-2 cells Concentration: 0.5, 1 μM Incubation Time: 24 hours Result: Induces cell cycle arrest in G0/G1 phase. Western Blot Analysis[1] Cell Line: Jurkat cells Concentration: 0.3 μM Incubation Time: 48 hours Result: Showed a first spike of activation of AMPKα after 30 minutes of treatment and a later increase in the phosphorylation of T172. The increase in S79 phosphorylation of its main target ACC (acetyl-coenzyme A (CoA) carboxylase), followed the same pattern. This rapid activation of AMPK, in turn induced a consequent reduction in mTOR phosphorylation that is visible already at 30’ and that becomes amplified at longer time probably due to the interruption of feedback loops that are characteristic of mTOR connecting pathways.
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