cIAP-1 Ligand

IAP ligand 9 is an ASX-series, non-peptidic SMAC mimetic and IAP binder with high cell permeability. IAP ligand 9 selectively targets cIAP1-BIR3, XIAP-BIR3, exhibits extremely weak binding affinity for XIAP-BIR2, with a K_D of 100 nM for cIAP1-BIR3 and 10 nM for XIAP-BIR2. IAP ligand 9 can be used to synthesize IAP-recruiting protein degraders (IPD), and can calibrate the cell permeability and cellular-level target binding assays of the IPD molecule SNIPER (TEAD)-1 (HY-181607). IAP ligand 9 and its series of degraders can be used in the research of solid tumors such as malignant pleural mesothelioma associated with abnormal activation of the Hippo pathway.

IAP ligand 8 is an ASX-series, non-peptidic SMAC mimetic and IAP binder with high cell permeability. IAP ligand 8 selectively targets cIAP1-BIR3, XIAP-BIR2 (with a K_D of 15.8 nM for both). IAP ligand 8 serves as an IAP ligand moiety to synthesize IAP-recruiting protein degrader (IPD) (HY-181590). This IPD simultaneously forms two ternary complexes, cIAP1-A538-TEAD1 and XIAP-A538-TEAD1, and efficiently degrades TEAD1 via a dual E3 recruitment mechanism, while inducing the autodegradation of cIAP1. IAP ligand 8 and its series of degraders are applicable to targeted research on Hippo pathway-dysregulated cancers such as NF2-mutant mesothelioma.