XIAP Degrader

GT19630 is an orally active c-Myc PROTAC targeted degrader based on the cereblon E3 ubiquitin ligase, with an IC₅₀ of 1.5 nM against human c-Myc. GT19630 mediates the degradation of MYC, GSPT1, GSPT2, CK1 alpha, N-Myc, B7-H3 and XIAP, and disrupts the MYC-GSPT1 synergistic regulatory feedback loop. GT19630 inhibits cell proliferation, blocks S-phase progression of the cell cycle, promotes cell apoptosis, reduces cell migration capacity, induces integrated stress response, and blocks oxidative phosphorylation by inhibiting the TCA cycle. GT19630 can be used in the research of Myc-driven hematological cancers, small cell lung cancer, breast cancer, TP53-mutant cancers, and venetoclax-resistant cancers.

XIAP degrader-1 is a PROTAC-like degrader with a K_d value of 1 μM for XIAP. XIAP degrader-1 is metabolized into an active aldehyde species that covalently binds to Cys326 of FBXO22, thereby forming a ternary complex with the BIR2 domain of XIAP. XIAP degrader-1 induces polyubiquitination and proteasomal degradation of XIAP via the ubiquitin-proteasome system, a process dependent on NEDD8 conjugation, the SCF^FBXO22 ligase complex, as well as the functional activities of XIAP ligase, E1 and the proteasome.

TD1092 is a pan-inhibitor of apoptosis protein (IAP) PROTAC degrader that targets cIAP1, cIAP2, and XIAP for degradation. TD1092 induces cell apoptosis by activating caspase. TD1092 inhibits the NF-κB signaling pathway induced by TNFα. TD1092 suppresses TNFα-induced epithelial-mesenchymal transition, cancer cell migration, and invasion. TD1092 is suitable for research on breast cancer, ovarian cancer, melanoma, and inflammation-related diseases.

CST626 is a PROTAC degrader targeting IAP, with DC₅₀ values of 0.7 nM, 2.4 nM and 6.2 nM against XIAP, cIAP1 and cIAP2, respectively. This compound recruits the VHL E3 ubiquitin ligase to form a heterotrimeric complex, thereby inducing ubiquitination and proteasomal degradation of the target proteins. CST626 also exhibits certain degrading activity against VHL30 and VHL19. CST626 inhibits the proliferation and induces apoptosis of various hematologic tumor cell lines, and its anti-tumor effect is further enhanced when used in combination with TNF-α. CST626 can be used in research related to multiple myeloma, acute myeloid leukemia and diffuse large B-cell lymphoma.