Humanwell Healthcare (Group) Co. Ltd. has described proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase binding moiety covalently linked to an interleukin-1 receptor-associated kinase 4 (IRAK-4) targeting moiety via a linker reported to be useful for the treatment of cancer, rheumatoid arthritis, renal disorders, multiple sclerosis, alopecia areata, urticaria, psoriasis and chronic obstructive pulmonary disease (COPD), among others.

Enhanced quantity and functionality of natural killer (NK) cells in hepatocellular carcinoma (HCC) have been associated with improved prognosis and survival. Therefore, NK cell-based immunotherapy has been proposed for treating HCC, relying on the activation of NK cell receptors like natural cytotoxicity receptors (NCRs), which recognize specific ligands on HCC cells. However, the effectiveness of this approach remains low due to tumor immune evasion.

Targeted protein degradation (TPD) is an alternative to conventional protein inhibition that is gaining attention due to advantages such as ensuring complete elimination of the target protein, reduced off-target effects or the potential to target previously inaccessible or “undruggable” proteins. Proteolysis targeting chimeras (PROTACs) are agents used for TPD that have proven effective for degradation of histone deacetylase (HDAC), among other different proteins.

Shanghai Yidi Biotechnology Co. Ltd. has synthesized proteolysis targeting chimeras (PROTACs) comprising an E3 ubiquitin ligase coupled to an androgen receptor targeting moiety via a linker reported to be useful for the treatment of spinal and bulbar muscular atrophy, prostate and breast cancer.

Etern Biopharma (Shanghai) Co. Ltd. has identified proteolysis targeting chimeras (PROTACs) comprising an E3 ubiquitin ligase binding moiety coupled to an androgen receptor targeting moiety through a linker acting as androgen receptor degradation inducers reported to be useful for the treatment of cancer.

Increland has identified proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase binding moiety covalently linked to an interleukin-1 receptor-associated kinase 4 (IRAK-4) targeting moiety via a linker. They are described as potentially useful for the treatment of psoriasis.

The University of Michigan has synthesized proteolysis targeting chimeras (PROTACs) comprising a von Hippel-Lindau disease tumor suppressor (VHL)-binding moiety coupled to a signal transducer and activator of transcription 3 (STAT3)-targeting moiety via a linker.

Son of sevenless homolog 1 (SOS1) is an essential guanine nucleotide exchange factor (GEF) in KRAS-driven tumors, and it also functions as a downstream node protein of BCR-ABL, suggesting its critical role in the pathogenesis of chronic myeloid leukemia (CML). Investigators at Shanghaitech University have reported the discovery and preclinical characterization of a novel potent SOS1 proteolysis targeting chimera (PROTAC) – SIAIS-562055 – being developed as an anticancer agent.

Fox Chase Chemical Diversity Center Inc. and University of Pittsburgh have jointly described new proteolysis targeting chimeras (PROTACs) consisting of Nef (HIV-1)-targeting moiety covalently linked to cereblon (CRBN)-binding moiety.