TL13-12 is PROTAC selectively targeting on ALK with DC50 values of 10nM and 180nM in H3122 and Karpas 299 cells, respectively, consist of an ALK-binding TAE684 ligand linked to Pomalidomide.
TL13-12 is PROTAC selectively targeting on ALK with DC50 values of 10nM and 180nM in H3122 and Karpas 299 cells, respectively, consist of an ALK-binding TAE684 ligand linked to Pomalidomide. TL13-12 exhibited anti-proliferative effect on H3122, Karpas 299, SU-DHL-1, Kelly, Lan5 with 21.3, 2.6, 1.4, 95 and 17nM, respectively, post 72-hour treatment, but with much less potency to SH-SY5Y and CHLA20 cells. The co-treatment with P-gp inhibitor Tariquidar (125nM) could improve the anti-proliferative potency of TL13-12 on Kelly, Lan5, SH-SY5Y and CHLA20 cells. TL13-12 achieved max degradation of ALK in H3122 and Karpas 299 cells at concentration of 500nM post 16h, but with a significant degradation of Aurora A observed. The phosphorylation levels of ALKY1604 site and its downstream STAT3Y705 phosphorylation site were decreased post 6-48h accompanied with the degradation of ALK protein by TL13-12 (250nM) in H3122 and Karpas 299 cells. Different from TL13-112, TL13-12 exhibited degradation activity on Aurora A at concentration ranging in 20-160nM in Kelly and CHLA20 (co-treated with Tariquidar) cells post 16h. TL13-22 is a negative control for TL13-12[1].
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