leukemic

BETd-260, a PROTAC linked by a Cereblon ligand and a BET ligand, has an inhibitory effect on BRD4 protein in leukemic cell lines.

SJ 11646, a potent lymphocyte-specific protein tyrosine kinase (LCK) Degrader (PROTAC) with a DC50 of 0.00838 pM, utilizes Dasatinib as the LCK ligand and incorporates a phenyl glutarimide-based cereblon binder. Demonstrating cytotoxicity in both LCK-activated T cell acute lymphoblastic leukemia (T-ALL) cell lines and primary leukemia samples in vitro, SJ 11646 also exhibits anti-leukemic efficacy in vivo within patient-derived xenograft models of T-ALL.

MD-265 is a PROTAC degrader that targets and degrades MDM2, leading to the activation of p53 in cancer cells with wild-type p53. MD-265 achieves complete tumor regression and enhances long-term survival in leukemic mice.

DP-15 acts as a degrader of GSPT1 and BRD4, with DC50 values of 5.25 nM and 0.48 nM, respectively. This compound exhibits antiproliferative activity in AML and NHL cells, showing IC50 values in the nanomolar range, induces G1 phase cell cycle arrest, and triggers apoptosis in MOLM13 cells. Additionally, DP-15 demonstrates anti-leukemic properties in the MOLM-13 xenograft mouse model. [Pink: ligand for target protein JQ-1 carboxylic acid; Black: linker; Blue: ligand for E3 ligaseCereblonThalidomide-5-OH]