rs4;11

MD-224 is a highly potent and efficacious MDM2 degrader based on the proteolysistargeting chimera (PROTAC) concept,and as a new class of anticancer agent.

PROTAC BET degrader-2 is a highly potent degrader of Bromodomain and Extra-Terminal (BET) proteins, with an IC50 of 9.6 nM.

Lenalidomide-C4-NH2 hydrochloride is a Cereblon ligand derived from Lenalidomide. It serves as a recruiting agent for the CRBN protein. The compound, known as PROTAC (Compound 24), can be formed by linking Lenalidomide-C4-NH2 hydrochloride to the ligand for the protein. It exhibits inhibitory effects with IC50s of 0.98 nM and 13.7 nM against the growth of RS4;11 and MOLM-13 acute leukemia cell lines, respectively[1].

KT-253 is a p53 stabilizer and a PROTAC degrader of MDM2 (DC50=0.4 nM). It inhibits the proliferation of cancer cells RS4;11 with an IC50 of 0.3 nM, induces cell cycle arrest in the G2/M phase, and triggers apoptosis. In mouse models, KT-253 demonstrates antitumor activity. (Pink: ligand for target protein MDM2 ligand 4; Black: linker; Blue: ligand for E3 ligase cereblon)

MD-4251 is an orally active MDM2 PROTAC degrader. It potently degrades MDM2 in RS4;11 cells (DC50: 0.2 nM) and activates p53. MD-4251 exhibits strong antiproliferative activity against acute leukemia cells with wild-type p53, but shows limited efficacy in mutant cells. In RS4;11 xenograft mouse models, MD-4251 induces complete tumor regression.

U7D-1, a groundbreaking and selective ubiquitin-specific protease 7 (USP7) PROTAC degrader, exhibits a DC50 value of 33 nM in RS4;11 cells, demonstrating its potent anticancer properties. Furthermore, U7D-1 effectively induces apoptosis in Jeko-1 cells [1].

AD4 is an artemisinin-derived proteolysis targeting chimera that selectively degrades PCLAF protein with subnanomolar potency in RS4;11 leukemia cells,AD4 leads to activation of the p21/Rb signaling axis, robust anti-tumor activity, and significantly prolonged survival in RS4;11 xenograft NOD/SCID mouse models, demonstrating both in vitro and in vivo therapeutic efficacy.

XM-U-14 is a selective PROTAC USP7 degrader that induces the degradation of USP7 in the RS4;11 cell line with a DC50 of 0.74 nM. This compound elevates the levels of p53 and p21, and significantly inhibits the growth of acute lymphoblastic leukemia (ALL) cells, with IC50 values of 0.5 nM in RS4;11 cells and 8.3 nM in Reh cells. Moreover, XM-U-14 induces apoptosis and cell cycle arrest, and effectively inhibits tumor growth.