Polo-like Kinase (PLK) Inhibitor

Scytonemin is a hydrophobic alkaloid pigment that can be isolated from the outer sheath of cyanobacteria. Scytonemin has protective function against short-wave solar ultraviolet (UV) radiation, which can reduce the generation of reactive oxygen species (ROS) and the formation of DNA damage. Scytonemin also has anti-inflammatory and anti-proliferative activities, produces concentration-dependent inhibition (IC₅₀=2.0 μM) of polo-like kinase 1 (PLK1)-mediated cdc25C phosphorylation, and plays an important role in regulating the G2/M transition in the cell cycle. It can be used in the research of cancer, acute inflammation and sunscreen cosmetics.

3MB-PP1, a bulky purine analog, is a Polo-like kinase 1 (Plk1) inhibitor. 3MB-PP1 blocks mitotic progression and cell division arise through target Plk1 in in cells expressing analog-sensitive Plk1 alleles. 3MB-PP1 specifically inhibits the activity of analog-sensitive Ssn3 (Cdk8). 3MB-PP1 inhibits Leu93 Mutant Zipper-interacting protein kinase (Leu93-ZIPK; IC₅₀=2 μM). 3MB-PP1 can be used for the research of hypha formation of Candida albicans and cell division.

TC-S 7005 is a Polo-like kinases (Plks) inhibitor with IC₅₀s of 4 nM, 24 nM and 214 nM for Plk2, Plk3, and Plk1, respectively.

Poloxin is a non-ATP competitive Polo-like Kinase 1 (PLK1) inhibitor that targets the polo-box domain, with an IC₅₀ of appr 4.8 μM.

Telocinobufagin (Telobufotoxin; Telocinobufogenin) is an orally active bufadienolide with potential anti-tumor effects. Telocinobufagin exerts its anti-cancer effects on non-small cell carcinoma, osteosarcoma, thyroid cancer, breast cancer and head and neck squamous cell carcinoma by inhibiting the STAT3, JAK2/STAT3, LARP1-mTOR, PI3K/Akt/Snail and PLK1 pathways, and can also induce tumor cell apoptosis. Telocinobufagin enhances the Th1 immune response and protects against Salmonella typhimurium infection. Telocinobufagin has a strong cardiac-stimulating effect by inhibiting the activity of Na⁺/K⁺-ATPase, and it can promote renal fibrosis. Telocinobufagin demonstrates non-opioid analgesic effects in various acute pain models.

RP-1664 is a selective and orally active PLK4 inhibitor with an IC₅₀ of 3 nM. RP-1664 demonstrates exquisite selectivity over related kinases, including AURKA/B and PLK1. RP-1664 disrupts centriole biogenesis in cancer cells and leads an accumulation of PLK4 and p21 protein. RP-1664 demonstrates increased sensitivity in TRIM37-high-expressing cells or tumors. RP-1664 exhibits anti-tumor activity in breast cancer and neuroblastoma research^[1][2].

KHS101 is a blood-brain barrier-penetrant anticancer agent that primarily functions by inhibiting HSPD1 (IC₅₀ = 14.4 μM) and TACC3 across different cellular backgrounds. KHS101 promotes the aggregation of HSPD1 with client proteins, destabilizes TACC3, and reduces the levels of TACC3, Aurora A and PLK1. KHS101 induces autophagy, apoptosis, cell cycle exit and neuronal differentiation; it suppresses cancer cell growth, motility, EMT and stemness; it also impairs mitochondrial bioenergetics and glycolysis in glioblastoma cells. KHS101 can be used in research related to glioblastoma multiforme and breast cancer.

BI2536-PEG2-Halo is a bifunctional molecule containing a ligand for Halo tag and a Polo-like kinase 1 (PLK1) inhibitor BI-2536 (HY-50698). BI2536-PEG2-Halo inhibits the proliferation of 293T cells with Halo-p53R273H(FL)-mCherry tag (IC₅₀=23 nM), exhibits selective toxicity against p53 mutant cancer cells.

Plogosertib (CYC140) is a selective, potent, and orally active ATP-competitive PLK1 inhibitor (IC₅₀: 3 nM). Plogosertib is an anti-cancer agent with anti-proliferative activity. Plogosertib can be used in the research of several tumors, including esophageal, gastric, leukemia, non–small cell lung cancer, ovarian, and squamous cell cancers.

SBE13 Hydrochloride is a potent and selective Plk1 inhibitor, with an IC₅₀ of 200 pM; SBE13 Hydrochloride poorly inhibits Plk2 (IC₅₀>66 μM) or Plk3 (IC₅₀=875 nM).

HMN-176 is a stilbene derivative which inhibits mitosis, interfering with polo-like kinase-1 (plk1), without significant effect on tubulin polymerization.

Lasiokaurin is an anticancer agent. Lasiokaurin can be isolated from Rabdosia rubescens (Hemsl.) H. Hara. Lasiokaurin inhibits the function of the PDPK1-AKT axis, with a K_d value of 75.93 μM for PDPK1. Lasiokaurin inhibits mTOR, STAT3, MAPK and NF-κB. Lasiokaurin reduces the mRNA and protein expression levels of PLK1. Lasiokaurin decreases DNA synthesis levels, induces cell Apoptosis, and regulates Autophagy processes. Lasiokaurin inhibits tumor growth in xenograft models. Lasiokaurin can be used in research related to nasopharyngeal carcinoma, triple-negative breast cancer.

PLK1/BRD4-IN-5 (Compound SC10) is an orally active PLK1 and BRD4 inhibitor with IC₅₀ values of 0.3  nM and 60.8  nM, respectively. PLK1/BRD4-IN-5 can induce MV4-11 cell block in S phase and apoptosis) in a dose-dependent manner. PLK1/BRD4-IN-5 can be used in cancer research.

PLK4-IN-4 (compound 22) is a potent PLK4 inhibitor with an IC₅₀ value of 7.9 nM. PLK4-IN-4 has the potential for the research of cancer.

Aurora kinase-IN-3 (Compound 15a) is an orally active AURKB inhibitor that elicits an AURKB-suppressive activity by disrupting the mitotic localization of AURKB, rather than inhibiting its phosphorylation of H3 at Ser10.

LFM-A13 is a potent BTK, JAK2, PLK inhibitor, inhibits recombinant BTK, Plx1 and PLK3 with IC₅₀s of 2.5 μM, 10 μM and 61 μM; LFM-A13 shows no effects on JAK1 and JAK3, Src family kinase HCK, EGFR and IRK.

PMV6-PEG4-BI2536 is an RIPTAC-like bifunctional molecule that promotes the formation of the p53^Y220C-PLK1 ternary complex (EC₅₀ = 1.4 μM). PMV6-PEG4-BI2536 causes PLK1 mislocalization and inhibits PLK1 activity, inducing G2/M phase arrest and apoptosis in p53^Y220C-mutant cells, while sparing cells with wild-type TP53. PMV6-PEG4-BI2536 can be used in research on uterine, gastric, pancreatic, prostate, and breast cancers harboring the p53^Y220C mutation. PMV6-PEG4-BI2536 is composed of PMV6 (a p53^Y220C mutant-binding ligand), PEG4 (a linker), and BI2536 (HY-159493) (a PLK inhibitor).

Volasertib (BI 6727) trihydrochloride is an orally active, highly potent and ATP-competitive Polo-like kinase 1 (PLK1) inhibitor with an IC₅₀ of 0.87 nM. Volasertib trihydrochloride inhibits PLK2 and PLK3 with IC₅₀s of 5 and 56 nM, respectively. Volasertib trihydrochloride induces mitotic arrest and apoptosis. Volasertib trihydrochloride, a dihydropteridinone derivative, shows marked antitumor activity in multiple cancer models.

AAPK-25 is a potent and selective Aurora/PLK dual inhibitor with anti-tumor activity, which can cause mitotic delay and arrest cells in a prometaphase, reflecting by the biomarker histone H3^Ser10 phosphorylation and followed by a surge in apoptosis. AAPK-25 targets Aurora-A, -B, and -C with K_d values ranging from 23-289 nM, as well as PLK-1, -2, and -3 with K_d values ranging from 55-456 nM.

LFM-A13 is a potent BTK, JAK2, PLK inhibitor, inhibits recombinant BTK, Plx1 and PLK3 with IC₅₀s of 2.5 μM, 10 μM and 61 μM. LFM-A13 has antiproliferative activity and anticancer activity. LFM-A13 can be used in cancer-related research