TL13-12

TL13-12 is a CRBN-recruiting ALK PROTAC degrader, with a DC₅₀ of 10 nM in H3122 cells. TL13-12 induces dimerization of CRBN and truncated ALK, which brings the DNA-binding domain and transactivation domain into close proximity, thereby activating the expression of downstream reporter genes, while exhibiting extremely low leaky expression under non-inducing conditions. TL13-12 serves as a tool molecule for the orthogonal PROTAC-CID system, and is applied in research on non-small cell lung cancer, anaplastic large cell lymphoma, and neuroblastoma^[1][2]. IC50 & Target:IC50: 0.69 nM (ALK)^[1] In Vitro:TL13-12 (2 days) induces activation of the EYFP reporter gene in HEK293T cells via a PROTAC-CID system that enables dimerization of CRBN and truncated ALK, with almost no basal leaky expression^[2].
TL13-12 (2 days) selectively induces firefly luciferase reporter gene activation in HEK293T cells expressing the cognate GAL4-tALK and CRBN-VPR protein pair, which demonstrates the orthogonal function of the PROTAC-CID system^[2].
TL13-12 (0.1 pM-10 µM) inhibits ALK kinase activity, with potency comparable to that of its parent inhibitor NVP-TAE 684 (TAE684) (HY-10192)^[1].
TL13-12 (4 h) induces significant degradation of PTK2, FER, RPS6KA1, and Aurora A in Kelly neuroblastoma cells, while no significant degradation of ALK is detected at this time point^[1].
TL13-12 (compound 9) (72 h) inhibits the proliferation of H3122, Karpas 299 and SU-DHL-1 cells, with potency comparable to its parent inhibitor TAE684^[1].
TL13-12 (0.01-1 μM; 16 h) induces proteasome-mediated degradation of ALK, with a DC₅₀ of 10 nM in H3122 cells and a DC₅₀ of 180 nM in Karpas 299 cells. In both cell lines, its degradative effect peaks at 16 h, and it exhibits higher selectivity for ALK than for Aurora A compared to compound 11^[1].
TL13-12 (50-250 nM; 16 h) exhibits comparable inhibitory effects on ALK downstream signaling to TAE684 in H3122 cells, with the inhibitory activity persisting for 48 h, while its inhibitory effect in Karpas 299 cells is relatively weak^[1].
TL13-12 (72 h) inhibits the proliferation of ABCB1-low-expressing Kelly and LAN5 neuroblastoma cells, but its potency decreases in ABCB1-high-expressing SH-SY5Y and CHLA20 cells; its activity is restored when combined with 125 nM Tariquidar (HY-10550)^[1].
TL13-12 (10-160 nM; 2-16 h) induces ALK degradation in Kelly neuroblastoma cells with a DC₅₀ of 50 nM; degradation is detected at 8 h in Kelly cells, while degradation is detected at 4 h in CHLA20 cells (co-treated with 125 nM P-glycoprotein inhibitor Tariquidar); moreover, its selectivity for ALK is higher than that of compound 11 in both cell lines^[1].
TL13-12 (50-250 nM; 16 h) exhibits comparable potency to NVP-TAE 684 (TAE684) (HY-10192) in inhibiting ALK downstream signaling in Kelly neuroblastoma cells, with the inhibitory effect persisting for more than 48 h, and shows stronger inhibition of ALK downstream signaling than TAE684 in CHLA20 cells (co-treated with 125 nM Tariquidar), with the inhibitory effect maintained for over 48 h^[1].