Once favorable drug candidates are identified, their therapeutic specificity and potency needs to be further validated. The modes of action of these leading drug candidate compounds are confirmed and further functional bioactivity testing is performed. Chemical interactions, degradation target specificity, CRBN dependent antiproliferative and/or other therapeutic activity, cell line specificity and pharmacokinetic / pharmacodynamic profiles are validated using a variety of biochemical, genetic, pharmacological, or degradation assays. Validation assays to confirm the chemical interactions of lead CELMods have included crystallography , docking analysis , fluorescence polarization assays , TR-FRET , and co-precipitation or pull down assays. Targets of degradation have been validated by immunoblotting , chemiluminescence based assays and expression proteomic analysis. Confirmation of the cellular activity of CELMods of interest have included antiproliferation assays across specific cell lines to validate the cell line specificity, potency, and therapeutic value of lead compounds. Identification of new targets for thalidomide analog molecular glue degraders E3 ubiquitin ligases recognize their substrates through degrons -short sections of primary protein sequence that are necessary and sufficient for the interaction with substrate receptors of ubiquitin ligases. Chemoproteomics provide a useful approach for identifying proteins from the human proteome with favorable degron features making these targets feasible candidates for recruitment to CRBN. IKZF1 and IKZF3 zinc finger proteins are essential transcription factors in multiple myeloma. After identifying a single Cys2-His2 (C2H2) zinc finger fold as the minimal sufficient degron necessary for IKZF1/IKZF3 degradation, the entire human C2H2 Zinc Finger proteome (>800 proteins) was screened for targets for thalidomideanalogue mediated degradation. Six proteins recruited for degradation were identified (including IKZF1/IKZF3), 4 of which were newly identified CRBN targets for thalidomide analogues. Further, through computational in silico docking analysis of all human C2H2 zinc fingers with CRBN, using the pomalidomide-CRBN crystal structure for structural similarity, about 50-150 CRBN binding zinc finger candidates were identified; 33 of these zinc fingers were further tested for in vitro CRBNpomalidomide binding and 28 (a remarkable 85% portion) tested positive for binding. New targets of therapeutic interest can be examined further to identify the optimal thalidomide analogue molecular glue degraders that stabilize the PPIs of CRBN with neosubstrates of interest. Sources of these optimal degraders could potentially be searched for among existing focused chemical library collections or through constructing new in silico assisted custom designed chemical libraries tailored for chemical feasibility and spatial diversity within the new CRBN-neosubstrate binding cavity space with physicochemical descriptors that lie within the drug-like property space. A chemical structure similarity search based on the thalidomide analog CC-885, performed by SciFinder-n , found 310 compounds within the 85-99% similarity range, exhibiting a wide variety of bioactivities, including antitumor, neurological, anti-infective, cardiovascular, etc. (Supplemental Information Figure ). Additionally, substructure searches can be useful for exploring previously synthesized analogs for inclusion in the construction of desired focused chemical libraries. A substructure search using an essential α,α-difluorobenzeneacetamide CC-885 analog scaffold identified 715 compounds retaining this exact chemical scaffold (Supplemental Information Figure ). SciFinder-n offers the possibility to screen the prospective library compounds for Lipinski properties and structure related properties such as: lipophilicity descriptor (log P), molecular weight (MW), Polar Surface Area (PSA), Hbond donors (HBD), and H-bond acceptors (HBA), confirming that physicochemical descriptors lie within a drug-like chemical property space, prior to library construction. Commercial availability and reaction synthesis details can also be explored. Thus, SciFinder-n appears as a powerful resource for the design of focused chemical libraries of potential molecular glues mediating the PPI of E3 ligase subunits and new prospective targets.