IAP 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.

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.

TD1092 is a pan-IAP degrader, degrades cIAP1, cIAP2, and XIAP. TD1092 activates Caspase 3/7, and promotes cancer cells apoptosis via IAP degradation. TD1092 inhibits TNFα mediated NF-κB pathway and reduces the phosphorylation of IKK, IkBα, p65, and p38. TD1092 can act as PROTAC, and is used for cancer research.

PROTAC TEAD1/IAP degrader-1 (Compound A232) is a selective TEAD1 and cIAP1 PROTAC degrader, with DC₅₀ values of 14 nM and 270 nM, respectively. PROTAC TEAD1/IAP degrader-1 promotes the ubiquitination and degradation of TEAD1 and cIAP1. PROTAC TEAD1/IAP degrader-1 downregulates the expression of the TEAD-dependent gene CTGF. PROTAC TEAD1/IAP degrader-1 exhibits anticancer activity against mesothelioma.

SM-122 is a monovalent Smac mimetic targeting cellular inhibitor of apoptosis protein (cIAP)-1/2. SM-122 can induce cIAP-1/2 degradation and weakly induce apoptosis in tumor cells. SM-122 can be used for the research of cancer, such as breast cancer.

MX107 is a selective and potent survivin inhibitor that suppresses triple-negative breast cancer (TNBC) cell proliferation. MX107 induces degradation of survivin and inhibitor-of-apoptosis proteins (IAPs), which inhibits nuclear factor κB (NF-κB) activation induced by DNA damage. MX107 enhances tumoricidal efficacy of genotoxic treatments synergized with chemotherapeutic drugs.

BCPyr is a PROTAC degrader targeting cIAP1 and BTK, with a K_d of 262 nM for human cIAP1, and K_d values of 262 nM and 692 nM for human BTK. BCPyr binds to the Bir3 domain of cIAP1, recruits BTK to cIAP1, and mediates the ubiquitination and degradation of BTK. BCPyr acts as a degrader, ternary complex stabilizer, cooperative binder, and higher-order assembly inducer. BCPyr can be used in studies related to leukemia and lymphoma.

PROTAC TEAD1/IAP degrader-3 is a TEAD1/IAP PROTAC degrader. PROTAC TEAD1/IAP degrader-3 recruits the cIAP1 and XIAP E3 ligases to form a ternary complex, drives proteasomal degradation of TEAD1, and triggers autoubiquitination and proteasomal degradation of cIAP1. PROTAC TEAD1/IAP degrader-3 inhibits cell proliferation. PROTAC TEAD1/IAP degrader-3 regulates Hippo pathway activity by downregulating CTGF gene expression in a TEAD-dependent manner. PROTAC TEAD1/IAP degrader-3 is applicable to the research of mesothelioma.

Ciapavir (SBI-0953294) is a HIV-1 latency-reversing agent. Ciapavir reverses latent HIV-1 reservoir in vitro and in vivo without inducing systemic T cell activation or broad cytokine release. Ciapavir degrades cIAP1 and activates non-canonical NF-κB pathway. Ciapavir can be used for the research of HIV-1 infection.

XIAP antagonist 1 degrades rather than inhibits XIAP, catalyzing rapid degradation of XIAP through the ubiquitin-proteasome pathway[2].

Anisomelic acid is a human papillomavirus HPV16 E6 and HPV E7 depletor. Anisomelic acid directly interacts with HPV16 E6, promotes its ubiquitination and proteasomal degradation by recruiting E3 ubiquitin ligase, downregulates E6 and facilitates E7 degradation. Anisomelic acid induces endogenous mitochondrial apoptosis, activates caspase-3, causes cleavage of PARP, and triggers p53-independent endogenous apoptosis by depleting cIAP2. Anisomelic acid can be used in research related to HPV-positive cancers and cervical cancer.