RIP kinase Degrader

PROTAC RIPK degrader-2 is a non-peptidic PROTAC degrader targeting RIPK2, with a DC₅₀ of 1.5 nM. PROTAC RIPK degrader-2 recruits VHL or cereblon E3 ubiquitin ligases, induces ubiquitination and proteasomal degradation of RIPK2, acts via substoichiometric catalysis, and inhibits downstream pro-inflammatory signaling pathways. PROTAC RIPK degrader-2 inhibits the NOD2/RIPK2 pathway and suppresses MDP (HY-127090)-stimulated TNFα release in human whole blood. PROTAC RIPK degrader-2 can be used in studies related to acute monocytic leukemia and glucose metabolism.

LD4172 is a selective RIPK1 PROTAC degrader with a K_i of 4.8 nM. LD4172 induces RIPK1 protein degradation via ternary complex formation with RIPK1 and VHL E3 ligase, driving ubiquitination and proteasomal breakdown. LD4172 abrogates TNF-induced classical NF-κB signaling in TRAF2-deficient cells, impairing IκBα phosphorylation and degradation, and reducing IL-8 production. LD4172 induces apoptosis and immunogenic cell death in tumor cells, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy. LD4172 acts as a chemical probe for investigating RIPK1 scaffolding functions. LD4172 can be used for the research of melanoma, colon cancer.

R1-ICR-5 is a highly selective RIPK1 PROTAC degrader. Mediated by VHL, R1-ICR-5 induces the degradation of RIPK1, which in turn dysregulates the TNFR1 and TLR3/4 signaling hubs, enhances the signaling outputs of NF-κB, MAPK and IFN, and simultaneously promotes RIPK3 activation and necroptosis (necroptosis). R1-ICR-5 can be used in the research of triple-negative breast cancer and skin inflammation.

PROTAC RIPK1 Degrader-1 is a selective RIPK1 PROTAC degrader. PROTAC RIPK1 Degrader-1 induces complete degradation of RIPK1 through the ubiquitin-proteasome system by bridging the target protein RIPK1 and VHL E3 ubiquitin ligase. PROTAC RIPK1 Degrader-1 is applicable to melanoma-related research.

LD5097 is a highly effective and selective PROTAC degrader targeting RIPK1. LD5097 can rapidly and efficiently downregulate RIPK1 and significantly enhance TNFα-mediated apoptosis in Jurkat cells. LD5097 significantly increases the levels of cleaved caspase-3/7 and PARP. LD5097 can be used for the study of acute T-lymphoblastic leukemia.