Non-PEG Linkers for Designing Proteolysis Targeting Chimera Molecules

Proteolysis targeting chimera molecules are bifunctional small molecules which consist of a ubiquitin E3 ligase ligand and a protein of interest (POI) ligand covalently bonded via a linker. The chimera molecules that induce the degradation of POI, while conventional molecules cannot, are regarded as a new drug modality. Although PEG linkers are typically used as linkers, the drug-like structures using non-PEG linkers with shorter linker length have been recently reported.^1,2) Non-PEG linkers, 1-Boc-4-(piperidin-4-ylmethyl)piperazine (1) and 1-Boc-4-(piperazin-1-ylmethyl)piperidine (2) can bind to various ligands. The proteolysis targeting chimera molecules derivatized from 1 or 2 are studied as potential oral drugs.

Related Products

D5965

1-Boc-4-(piperidin-4-ylmethyl)piperazine

D5966

1-Boc-4-(piperazin-1-ylmethyl)piperidine

Product Category Pages

• Homobifunctional Cross-Linkers
• Heterobifunctional Cross-Linkers
• Proteolysis Targeting Chimera Research Reagents

References

• 1) Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer
  • X. Han, L. Zhao, W. Xiang, C. Qin, B. Miao, D. McEachern, Y. Wang, H. Metwally, L. Wang, A. Matvekas, B. Wen, D. Sun, S. Wang, J. Med. Chem. 2021, 64, 12831.
• 2) Direct-to-Biology Accelerates PROTAC Synthesis and the Evaluation of Linker Effects on Permeability and Degradation
  • C. E. Hendrick, J. R. Jorgensen, C. Chaudhry, I. I. Strambeanu, J.-F.s Brazeau, J. Schiffer, Z. Shi, J. D. Venable, S. E. Wolkenberg, ACS Med. Chem. Lett. 2022, 13, 7, 1182.

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