Recent years have witnessed notable breakthroughs in the field of biotherapeutics. Proteolysis Targeting Chimeras (PROTACs) are novel molecules which used to degrade particular proteins despite the blockage by small drug molecules, which leads to a predicted therapeutic activity. This is a unique finding, especially at the cellular level targets degradations. Clinical trials and studies on PROTACs are in progress for oncology indications for demonstration of high potency and activity. PROTAC molecules are having excellent tissue distribution properties and their capacity to mutate the proteins and target overexpressed. This concept has attained wide attention from modern researchers in oncological drug discovery with particular physical qualities not offered by other therapeutic approaches. The modular nature of the PROTACs enables their methodical optimization and logical design. A thorough review was conducted in order to delve deeper into the subject and gain a better understanding of its development, computational supports, important factors for the optimization of developed PROTAC candidates, pharmacokinetic and pharmacodynamic (PK-PD) aspects, safety risks such as the degradation of undesired proteins, and other PROTAC-related issues and their target immunotherapeutic response. Furthermore discussed about the benefits, possible challenges, viewpoints, comparison with other targeted protein degraders (LYTACs, AUTOTACs) and the most current research results of PROTACs technology in multiple oncology therapies. Abbreviations: PROTACs, Proteolysis Targeting Chimeras
PK, Pharmacokinetic
PD, Pharmacodynamic
MetAP-2, (methionine aminopeptidase 2)
BCL6, B-cell lymphoma 6
GCN5, General Control Nonderepressible 5
BKT, Bruton's tyrosine kinase
BET, Bromodomain and extra-terminal
AR, Androgen or Androgen receptor
ER, Estrogen or Estrogen receptor
FDA, Food and Drug Administration
mCRPC, Metastatic castration-resistant prostate cancer
STAT3, Signal Transducer and Activator of Transcription 3
FAK, Focal adhesion kinase
POI, Protein of interest
PEG, Polyethylene glycol
UPS, Ubiquitin-Proteasome System
VHL, Von Hippel-Lindau
CRBN, Cereblon
MDM2, Mouse Double Minute 2 homologue
cIAP, Cellular Inhibitor of Apoptosis
RNF, Ring Finger Protein
BRD, Bromodomain
CDK, Cyclin-dependent kinase
PAMPA, Parallel Artificial Membrane Permeability studies
BRET, Bioluminescence Resonance Energy Transfer
MCL, Mantle cell lymphoma
MCL-1, Myeloid Cell Leukemia 1
BCL-X