Checkpoint Kinase (Chk) Degrader

PROTAC Chk1 degrader-1 is a Chk1-targeting PROTAC.PROTAC Chk1 degrader-1 recruits the Cereblon E3 ligase to induce ubiquitination and proteasomal degradation of Chk1.PROTAC Chk1 degrader-1 exhibits Chk1 degradation activity in malignant melanoma cells without showing a hook effect.PROTAC Chk1 degrader-1 can be used for the research of malignant melanoma.

MA203 is a highly efficient and selective PROTAC degrader targeting CHK1. MA203 accelerates CRBN-dependent proteasomal degradation of CHK1 in solid tumor-derived cells and acute leukemia cells. MA203 induces DNA replication stress. MA203 blocks cell cycle progression and triggers tumor cell apoptosis. MA203 does not damage healthy differentiated and primitive hematopoietic cells, stromal cells, and retinal epithelial cells. MA203 can be used for the study of CHK1-dependent cancers.

PROTAC ATR degrader-3 is a potent CRBN-based ATR PROTAC degrader with a DC₅₀ of 127 nM. PROTAC ATR degrader-3 also degrades CHK1 with an DC₅₀ of 135 nM. PROTAC ATR degrader-3 inhibits cancer cells proliferation, migration and invasion, triggers apoptosis and induces S phase arrest and DNA damage. PROTAC ATR degrader-3 achieves tumor growth inhibition in LoVo xenograft mouse model without apparent toxicity. PROTAC ATR degrader-3 can be used for the research of colorectal cancer.

PROTAC FLT3/CHK1 Degrader-1 is a PROTAC FLT3/CHK1 degrader, with DC₅₀ values of 5.88 nM (FLT3) and 4.17 nM (CHK1), respectively. PROTAC FLT3/CHK1 Degrader-1 can inhibit the phosphorylation of FLT3 downstream signaling effectors STAT5 (Tyr694), AKT (Ser473), and ERK (Tyr204), downregulate the protein level of c-Myc and maintain the expression of p53 protein. PROTAC FLT3/CHK1 Degrader-1 induces apoptosis in MV-4-11 cells. PROTAC FLT3/CHK1 Degrader-1 shows significant anti-tumor efficacy in mice bearing MV-4-11 subcutaneous xenografts. PROTAC FLT3/CHK1 Degrader-1 can be used for the study of acute myeloid leukemia (AML).