LD2 is a protein arginine N-methyltransferase 9 (PRMT9) inhibitor. It inhibited the viability of leukemia cells (IC50 = 2-7 µM in various cell lines). LD2 promoted DNA damage leading to cyclic GMP-AMP synthase (cGAS) activation and a type I IFN response. LD2 acted synergistically with anti-PD-1 mAb in an A20 lymphoma syngeneic model, an MA9 AML transplant model as well as a humanized AML mouse model. LD2 treatment led to leukemia stem cell ablation as well as an anticancer immune response.
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