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. 2022 Jun 14;23(12):6630. doi: 10.3390/ijms23126630

Figure 1.

Figure 1

(A) Prototypical structure of a Proteolysis Targeting Chimeric Molecules (PROTAC) based on the example of dBET23 PROTAC (Protein Data Bank number 6BN7). PROTACs favor the formation of a ternary complex involving the PROTAC itself (cyan structure), a protein of interest (POI) in the case of the DNA damage-binding protein 1 (green surface), and a cell E3 ligase in the case of the Protein cereblon (pink surface). This is made available by the coexistence, in the same molecule, of a POI-binding moiety and an E3 ligase-binding moiety (in the case of thalidomide) joined by a linker of suitable length. (B) A list of PROTACS involved in clinical trials. Abbreviations: AR—androgen receptor; ER—oestrogen receptor; BCL-xL—B cell lymphoma- extra-large; BRD9—bromodomain-containing protein 9; BTK—Bruton’s tyrosine kinase; EGFR-L585R—epidermal growth factor receptor harboring the exon point mutation L858R; ER—oestrogen receptor; HS—hidradenitis suppurativa; IND-e—IND- enabling preclinical studies; IRAK4—interleukin-1 receptor-associated kinase 4; STAT3—signal transducer and activator of transcription 3; TRK—tropomyosin receptor kinase. * Ingo Hartung su Twitter: “The plot thickens regarding the structure of IRAK4 PROTAC KT-474 @KymeraTx. 2 patents disclosing deuterated, crystalline & salt forms of a single PROTAC. Comprising a non-conventional CRBN binder the chemists at Kymera seem to like a lot. More common NH-linked IMiD in KT-413? https://t.co/O8JMRLZvpY”/Twitter (accessed on 1 March 2022).