ComInnex IAP Ligand Library

Description

• Application: The ComInnex IAP Ligand Library is an 80-member collection of in-silico-derived ligands targeting cellular inhibitor of apoptosis protein 1 (cIAP1). cIAP1 is an E3 ligase of interest for the development of protein degraders, specifically called specific and non-genetic IAP-dependent protein erasers (SNIPERs).Based on the SAR rules outlined in IAP antagonist research, the binding tetrapeptide anchor of the natural SMAC inhibitor protein of IAPs (AVPI and AVPF) was used in identification of novel derivatives designed by 3D similarity. The initial library was filtered via in silico IFD methods by docking to the BIR3 domain of the IAP crystal structures. The highest binding derivatives were selected and collected in a screening library, including the natural binding tetrapeptides and known MV1 reference compounds. IAP in silico leads are an optimal collection to begin IAP lead discovery at the bench for eventual development into bifunctional protein degraders. With the proper assay setup to measure protein degradation or protein-protein interactions (PPIs), the ComInnex IAP Ligand Library can also be a platform for molecular glue discovery.Learn more about this library: Accelerating IAP Lead Discovery for Targeted Protein DegradationTo view a complete list of compounds in the library, including sdf, visit the CIX001 Plate Map. To streamline the assessment of these in silico leads for target-specific bifunctional degraders, three IAP ligands with the highest docking scores were also prepared as degrader building blocks for simple attachment of a target warhead.
• Biochem/physiol Actions: 80 compounds are arranged in 96-microtube format with two open rows for screening controls if using liquid handling setups. One compound per tube (125 μg in solid form). Compound concentration in assays will vary depending on assay type, but common screening library stock solutions are 2 mM or 10 mM in DMSO.
• Other Notes: Inhibitor of Apoptosis Protein (IAP) Antagonists in Anticancer Agent Discovery: Current Status and PerspectivesDegrader Building Blocks (including CRBN- and VHL-targeting ligands)