LL-K12-18 is a two-site molecular glue that enhances the protein-protein interaction of the CDK12-DDB1 complex, stabilizing the CDK12-DDB1 complex and promoting the degradation of cyclin K ( EC 50 =0.37 nM). LL-K12-18 exhibits strong gene transcription inhibition and anti-proliferation effects in tumor cells. LL-K12-18 can be used in cancer research.