Publication

PROTACs- a game-changing technology

Konstantinidou, M., Li, J., Zhang, B., Wang, Z., Shaabani, S., Ter Brake, F., Essa, K. & Dömling, A., 2019, In : Expert Opinion on Drug Discovery. 14, 12, p. 1255-1268 14 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Konstantinidou, M., Li, J., Zhang, B., Wang, Z., Shaabani, S., Ter Brake, F., ... Dömling, A. (2019). PROTACs- a game-changing technology. Expert Opinion on Drug Discovery, 14(12), 1255-1268. https://doi.org/10.1080/17460441.2019.1659242

Author

Konstantinidou, Markella ; Li, Jingyao ; Zhang, Bidong ; Wang, Zefeng ; Shaabani, Shabnam ; Ter Brake, Frans ; Essa, Khaled ; Dömling, Alexander. / PROTACs- a game-changing technology. In: Expert Opinion on Drug Discovery. 2019 ; Vol. 14, No. 12. pp. 1255-1268.

Harvard

Konstantinidou, M, Li, J, Zhang, B, Wang, Z, Shaabani, S, Ter Brake, F, Essa, K & Dömling, A 2019, 'PROTACs- a game-changing technology', Expert Opinion on Drug Discovery, vol. 14, no. 12, pp. 1255-1268. https://doi.org/10.1080/17460441.2019.1659242

Standard

PROTACs- a game-changing technology. / Konstantinidou, Markella; Li, Jingyao; Zhang, Bidong; Wang, Zefeng; Shaabani, Shabnam; Ter Brake, Frans; Essa, Khaled; Dömling, Alexander.

In: Expert Opinion on Drug Discovery, Vol. 14, No. 12, 2019, p. 1255-1268.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Konstantinidou M, Li J, Zhang B, Wang Z, Shaabani S, Ter Brake F et al. PROTACs- a game-changing technology. Expert Opinion on Drug Discovery. 2019;14(12):1255-1268. https://doi.org/10.1080/17460441.2019.1659242


BibTeX

@article{a07f03b4d05a4bf485c04b54b6481581,
title = "PROTACs- a game-changing technology",
abstract = "Introduction: Proteolysis - targeting chimeras (PROTACs) have emerged as a new modality with the potential to revolutionize drug discovery. PROTACs are heterobifunctional molecules comprising of a ligand targeting a protein of interest, a ligand targeting an E3 ligase and a connecting linker. The aim is instead of inhibiting the target to induce its proteasomal degradation. Areas covered: PROTACs, due to their bifunctional design, possess properties that differentiate them from classical inhibitors. A structural analysis, based on published crystal aspects, kinetic features and aspects of selectivity are discussed. Specific types such as homoPROTACs, PROTACs targeting Tau protein and the first PROTACs recently entering clinical trials are examined. Expert opinion: PROTACs have shown remarkable biological responses in challenging targets, including an unprecedented selectivity over protein family members and even efficacy starting from weak or unspecific binders. Moreover, PROTACs are standing out from classical pharmacology by inducing the degradation of the target protein and not merely its inhibition. However, there are also challenges in the field, such as the rational structure optimization, the evolution of computational tools, limited structural data and the greatly anticipated clinical data. Despite the remaining hurdles, PROTACs are expected to soon become a new therapeutic category of drugs.",
keywords = "Degradation, PROTAC, structural analysis, article, chimera, clinical trial (topic), controlled study, crystal, drug efficacy, human, protein degradation, protein family, structure analysis, endogenous compound, proteasome, ubiquitin protein ligase",
author = "Markella Konstantinidou and Jingyao Li and Bidong Zhang and Zefeng Wang and Shabnam Shaabani and {Ter Brake}, Frans and Khaled Essa and Alexander D{\"o}mling",
year = "2019",
doi = "10.1080/17460441.2019.1659242",
language = "English",
volume = "14",
pages = "1255--1268",
journal = "Expert Opinion on Drug Discovery",
issn = "1746-0441",
publisher = "Taylor & Francis Group",
number = "12",

}

RIS

TY - JOUR

T1 - PROTACs- a game-changing technology

AU - Konstantinidou, Markella

AU - Li, Jingyao

AU - Zhang, Bidong

AU - Wang, Zefeng

AU - Shaabani, Shabnam

AU - Ter Brake, Frans

AU - Essa, Khaled

AU - Dömling, Alexander

PY - 2019

Y1 - 2019

N2 - Introduction: Proteolysis - targeting chimeras (PROTACs) have emerged as a new modality with the potential to revolutionize drug discovery. PROTACs are heterobifunctional molecules comprising of a ligand targeting a protein of interest, a ligand targeting an E3 ligase and a connecting linker. The aim is instead of inhibiting the target to induce its proteasomal degradation. Areas covered: PROTACs, due to their bifunctional design, possess properties that differentiate them from classical inhibitors. A structural analysis, based on published crystal aspects, kinetic features and aspects of selectivity are discussed. Specific types such as homoPROTACs, PROTACs targeting Tau protein and the first PROTACs recently entering clinical trials are examined. Expert opinion: PROTACs have shown remarkable biological responses in challenging targets, including an unprecedented selectivity over protein family members and even efficacy starting from weak or unspecific binders. Moreover, PROTACs are standing out from classical pharmacology by inducing the degradation of the target protein and not merely its inhibition. However, there are also challenges in the field, such as the rational structure optimization, the evolution of computational tools, limited structural data and the greatly anticipated clinical data. Despite the remaining hurdles, PROTACs are expected to soon become a new therapeutic category of drugs.

AB - Introduction: Proteolysis - targeting chimeras (PROTACs) have emerged as a new modality with the potential to revolutionize drug discovery. PROTACs are heterobifunctional molecules comprising of a ligand targeting a protein of interest, a ligand targeting an E3 ligase and a connecting linker. The aim is instead of inhibiting the target to induce its proteasomal degradation. Areas covered: PROTACs, due to their bifunctional design, possess properties that differentiate them from classical inhibitors. A structural analysis, based on published crystal aspects, kinetic features and aspects of selectivity are discussed. Specific types such as homoPROTACs, PROTACs targeting Tau protein and the first PROTACs recently entering clinical trials are examined. Expert opinion: PROTACs have shown remarkable biological responses in challenging targets, including an unprecedented selectivity over protein family members and even efficacy starting from weak or unspecific binders. Moreover, PROTACs are standing out from classical pharmacology by inducing the degradation of the target protein and not merely its inhibition. However, there are also challenges in the field, such as the rational structure optimization, the evolution of computational tools, limited structural data and the greatly anticipated clinical data. Despite the remaining hurdles, PROTACs are expected to soon become a new therapeutic category of drugs.

KW - Degradation

KW - PROTAC

KW - structural analysis

KW - article

KW - chimera

KW - clinical trial (topic)

KW - controlled study

KW - crystal

KW - drug efficacy

KW - human

KW - protein degradation

KW - protein family

KW - structure analysis

KW - endogenous compound

KW - proteasome

KW - ubiquitin protein ligase

U2 - 10.1080/17460441.2019.1659242

DO - 10.1080/17460441.2019.1659242

M3 - Article

VL - 14

SP - 1255

EP - 1268

JO - Expert Opinion on Drug Discovery

JF - Expert Opinion on Drug Discovery

SN - 1746-0441

IS - 12

ER -

ID: 98324617