PLK inhibiteurs (PLK Inhibitors)

Autre Cell Cycle Inhibiteurs

Produits sélectifs disoformes

• Inhibiteurs en vedette
• Inhibiteurs (18)

N° de cat.	Nom du produit	Informations	Citations dutilisation du produit	Validations de produit
S2235	Volasertib (BI6727)	Volasertib ist ein hochwirksamer Plk1-Inhibitor mit einer IC50 von 0,87 nM in einem zellfreien Assay. Er zeigt eine 6- und 65-fach höhere Selektivität gegen Plk2 und Plk3. Volasertib induziert Zellzyklusarrest und Apoptose in verschiedenen Krebszellen. Phase 3.	Leukemia, 2025, 10.1038/s41375-025-02729-w Cell Death Dis, 2025, 16(1):673 Cell Death Dis, 2025, 16(1):396
S1109	BI 2536	BI-2536 ist ein potenter Plk1-Inhibitor mit einer IC50 von 0,83 nM in einem zellfreien Assay. BI-2536 hemmt die Bromodomäne 4 (BRD4) mit einem Kd von 37 nM und unterdrückt potent die c-Myc-Expression. BI-2536 induziert Apoptose und dämpft die Autophagie. Phase 2.	Gut, 2025, gutjnl-2024-334274 Nat Commun, 2025, 16(1):1599 Genome Biol, 2025, 26(1):204
S1362	Rigosertib (ON-01910)	Rigosertib (ON-01910) ist ein nicht-ATP-kompetitiver Inhibitor von PLK1 mit einem IC50 von 9 nM in einem zellfreien Assay, der eine 30-fach höhere Selektivität gegenüber Plk2 und keine Aktivität gegenüber Plk3 zeigt. Es hemmt den PI3K/Akt-Signalweg, aktiviert oxidative Stresssignale und induziert Apoptose in verschiedenen Krebszellen. Diese Verbindung befindet sich in Phase 3.	Drug Resist Updat, 2025, 81:101251 Nat Commun, 2024, 15(1):2089 Environ Mol Mutagen, 2024, 10.1002/em.22604
S2193	GSK461364	GSK461364 (GSK461364A) hemmt gereinigtes Plk1 mit einem Ki von 2,2 nM in einem zellfreien Assay. Es ist mehr als 1000-fach selektiv gegenüber Plk2/3.	Exp Mol Med, 2025, 57(4):733-744 Sci Signal, 2022, 15(754):eabj4009 Cancers (Basel), 2022, 14(6)1575
S7255	Onvansertib (NMS-1286937, NMS-P937)	Onvansertib (NMS-1286937, NMS-P937) ist ein oral verfügbarer, selektiver Polo-like Kinase 1 (PLK1)-Inhibitor mit einer IC50 von 2 nM und einer 5000-fachen Selektivität gegenüber PLK2/PLK3. Diese Verbindung bewirkt potent einen mitotischen Zellzyklusarrest, gefolgt von Apoptose in Krebszelllinien, und hemmt das Tumorwachstum. Phase 1.	Nat Commun, 2025, 16(1):3605 J Mass Spectrom, 2025, 60(5):e5137 Cancer Res Commun, 2025, 5(4):648-667
S7552	CFI-400945	CFI-400945 ist ein oral aktiver, potenter und selektiver polo-like kinase 4(PLK4) Inhibitor mit einem Ki-Wert von 0,26 nM.	Commun Biol, 2025, 8(1):1011 Photochem Photobiol, 2025, 10.1111/php.70006 Transl Cancer Res, 2025, 14(6):3822-3832
S1485	HMN-214	HMN-214 ist ein Prodrug von HMN-176, das die zelluläre räumliche Orientierung von Plk1 verändert.	iScience, 2024, 27(10):110862 Cancers (Basel), 2022, 14(6)1575 Exp Mol Med, 2020, 10.1038/s12276-020-00537-z
S7248	Ro3280	RO3280 (Ro5203280) ist ein potenter, hochselektiver Inhibitor der Polo-like Kinase 1 (PLK1) mit einer IC50 von 3 nM.	JCI Insight, 2024, 9(8)e173205 Cancers (Basel), 2023, 15(9)2589 J Med Chem, 2021, 10.1021/acs.jmedchem.1c01096
S7720	SBE 13 HCl	SBE 13 HCl ist ein potenter und selektiver PLK1-Inhibitor mit einer IC50 von 200 pM und einer >4000-fachen Selektivität gegenüber Aurora A-Kinase, Plk2 und Plk3.	J Clin Invest, 2023, 133(21)e162129 PLoS Pathog, 2021, 17(7):e1009764 Reprod Biol Endocrinol, 2021, 19(1):162
S2898	MLN0905	MLN0905 ist ein potenter Inhibitor von PLK1 mit einem IC50 von 2 nM.	Science Bulletin, 2018, 10.1016/j.scib.2018.09.024 Hepatology, 2017, 10.1002/hep.29236
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PLKs - the Serine/Threonine protein kinases - are structurally comprised of a highly conserved catalytic domain in the N-terminus and a PBD in the C-terminus. The PDB domain is unique for the polo-like kinases family, and essential for their functions such as the subcellular localization and the substrate recognition. Mammalian polo-like kinases (PLK) consists of five members including PLK1 (STPK13), PLK2 (SNK), PLK3 (CNK, FNK or PRK), PLK4 (SAK or STK18), and PLK5. PLKs are critical regulators of cell cycle progression, mitosis, cytokinesis, and the DNA damage response. ^[1][2]

PLK1 is the most extensively studied member of this family. Through its PBD, PlK1 associates with a large number of proteins, some of which mediate its recruitment to defined cellular structures, such as the centrosomes, kinetochores and the spindle midzone. As reflected by multiple localizations, PLK1 is pivotal in the regulation of diverse cellular and biochemical events at multiple stages of the M phase, including entry into mitosis, centrosome maturation, assembly of the bipolar spindle, sister chromatid splitting, activation of the anaphase-promoting complex/cyclosome (APC/C) and exit from mitosis with the initiation of cytokinesis. As PLK1 is essential for cell division, inhibition of PLK1 leads to a failure to complete mitosis, eventually resulting in cell death. PLK2 is classified as an early growth response gene by virtue of its increased expression on stimulation by growth factors. PLK2 is up-regulated by p53 upon irradiation, and the depletion of PLK2 seems to phenocopy the loss of p53 by elevating the sensitivity of cells to spindle poisons. PLK2 is also implicated in centriole duplication, and functions as a regulator of synaptic plasticity in the nervous system. PLK3 is a multifunctional stress response protein. In response to different types of cellular stress, PLK3 activates Chk2 and p53, and plays an important role in genotoxic, hypoxic and oxidative stress responses. Endogenous ectopically expressed PLK3 localizes to the centrosomes during interphase, to the spindle poles during mitosis, and to the midbody during cytokinesis. The overexpression of wild-type or mutant forms of PLK3 induces G2/M arrest and eventually apoptosis. PlK4 is crucial for the duplication of the centrioles, and essential for early embryogenesis. The overexpression of PLK4 induces multinucleated cells that are associated with a progressive loss of cell viability. Although PLK5 has a truncated kinase domain that lacks kinase activity of catalytic activity, PLK5 retains important functions in neuron biology. Overexpression of PLK5 induces G1 cell cycle arrest followed by apoptosis. PLK5 can be induced by various stress-promoting agents, which is independent of p53 in contrast to PLK2 and PLK3. ^[1][2][3]

Polo-like kinases are dysregulated in a variety of human cancers. Consistent with the critical functions of PLK1 during M-phase progression, PLK1 is highly expressed in tumors including those derived from lung, breast, colon, pancreas, prostate and ovary. Over-expression of PLK1 correlates with cellular proliferation and poor prognosis, and PLK1 depletion is associated with a decrease in cell viability and induction of apoptosis in various cancerous cells, indicating that PLK1 is a promising target in oncology. Small-molecule inhibitors of PLK1 have become attractive candidates for anticancer drug development targeting the kinase domain and the PBD of PLK1, and a variety of PLK1 inhibitors (GW843682X, BI 2536, et al.) have been clinically assessed and hold great promise for the improved treatment of cancer patients. ^[1][2]