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. 2019 Jan 25;17:160–176. doi: 10.1016/j.csbj.2019.01.006

Table 3.

E3 protein ligand, structure of the linker and POI ligand with a description of the properties for (nuclear) receptors.

Table entry E3 protein (ligand) Linker POI ligand POI Potency/efficacy Reference
1. MDM2 (Nutlin) Image 63 Image 64 AR Upon treatment of HeLa cells with 10 μM compound for 7h, a decrease in androgen receptor levels was observed Schneekloth [26]
2. cIAP1 (Bestatin) Image 65 Image 66 CRABP-II Degradation of CRABP-II in IMR-32 cells was observed at 10 μM PROTAC concentration. Itoh [28] and Okuhira [29]
3. cIAP1 (Bestatin) Image 67 Image 68 RAR Maximal RAR degradation at 30 μM concentration in HT1080 cells Itoh [27]
4. cIAP1 (Bestatin) Image 69 Image 70 ERα Maximal ERα degradation at 30 μM concentration in human mammary tumor MCF7 cells Itoh [27]
5. cIAP1 (Bestatin)
Image 71 		Image 72 AR Maximal AR degradation at 30 μM concentration in human mammary tumor MCF7 cells Itoh [27]
6. VHL (9) Image 73 Image 74 ERRα 50% ERRα degradation at 100 nM. Protein knockdown in tumor xenografts (mouse) Bondeson [7]
7. HSP70 (adamantyl) Image 75 Image 76 AR DC50: 1.1 μM, Dmax: 69%. Anti-proliferative activity remained in castration-resistant prostate cancer cells Gustafson [113]
8. VHL (9) Image 77 Image 78 AR DC50: 5 nM, Dmax: 98%. ARCC-4 effectively degrades clinically relevant AR mutants. ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance Salami [114]

The structure of the CRBN ligands and the VHL ligand (9) are shown in Fig. 2.