TL13-112

TL13-112 is a potent and selective ALK-PROTAC degrader and inhibits ALK activity with an IC₅₀ value of 0.14 nM. TL13-112 also prompts the degradation of additional kinases including Aurora A, FER, PTK2 and RPS6KA1 with IC₅₀ values of 8550 nM, 42.4 nM, 25.4 nM, and 677 nM, respectively. TL13-112 is comprised of the conjugation of Ceritinib (HY-15656) and the Cereblon ligand of Pomalidomide (HY-10984)^[1]. IC50 & Target:IC50: 0.14 nM (ALK)^[1] In Vitro: TL13-112 binds to cereblon with an IC₅₀ value of 2.4 uM^[1].
TL13-112 (0.01 μM-1 μM; 16 hours) is selective for degradation of ALK with the DC₅₀s of 10 nM and 40 nM in H3122 cell and Karpas 299, respectively. ALK degradation acts at 4 hours of treatment in H3122 cells and at 8 hours of treatment in Karpas 299 cells. The maximum degradation achieves at 16 hours in both cell lines. ^[1].
TL13-112 (0.01 μM-1 μM; 16 hours) inhibits PTK2, ALK, FER, RPS6KA1 and Aurora A expression as a dose-dependent manner in H3122, Karpas 299, and Kelly cells^[1].