tl13-12

Description: TL13-12 is novel, potent and selective degrader of anaplastic lymphoma kinase (ALK) with DC50 values of 10 and 180 nM in H3122 and Karpas 299 cells, respectively. It comprises the cereblon E3 ligase ligand Pomalidomide conjugated to an ALK inhibitor. TL13-12 is the first small molecule degraders that can induce anaplastic lymphoma kinase (ALK) degradation, including in non-small-cell lung cancer (NSCLC), anaplastic large-cell lymphoma (ALCL), and neuroblastoma (NB) cell lines. TL13-12 was developed through conjugation of known pyrimidine-based ALK inhibitors, TAE684 or LDK378, and the cereblon ligand pomalidomide. In some cell types, the degrader potency is compromised by expression of drug transporter ABCB1. In addition, proteomic profiling demonstrated that these compounds also promote the degradation of additional kinases including PTK2 (FAK), Aurora A, FER, and RPS6KA1 (RSK1).

References: J Med Chem. 2018 May 10; 61(9):4249-4255.