PLK1 Inhibitor

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

BI 2536 is a dual PLK1 and BRD4 inhibitor with IC₅₀s of 0.83 and 25 nM, respectively. BI-2536 suppresses IFNB (encoding IFN-β) gene transcription.

NMS-1286937 is a potent, selective and orally available PLK1 inhibitor, with an IC₅₀ of 2 nM.

GSK461364 is a selective, reversible and ATP-competitive Polo-like kinase 1 (PLK1) inhibitor with a K_i value of 2.2 nM.

Rigosertib (ON-01910) is a multi-kinase inhibitor and a selective anti-cancer agent, which induces apoptosis by inhibition the PI3 kinase/Akt pathway, promots the phosphorylation of histone H2AX and induces G2/M arrest in cell cycle. Rigosertib is a selective and non-ATP-competitive inhibitor of PLK1 with an IC₅₀ of 9 nM.

MCC1019 is a selective PLK1 PBD inhibitor with an IC₅₀ of 16.4 μmol/L. MCC1019 inactivates the AKT signaling pathway in cancer cells, and induces Apoptosis, Necroptosis and Autophagy. MCC1019 exhibits anticancer activity against lung cancer and prostate cancer.

ZNL-02-096 is a selective Wee1 PROTAC degrader. ZNL-02-096 binds to CRBN and Wee1 to form a ternary complex, inducing CRBN- and proteasome-dependent ubiquitination and proteasomal degradation of Wee1. ZNL-02-096 inhibits recombinant PLK1 with an IC₅₀ of 102 nM, but does not induce its degradation in cells. ZNL-02-096 induces G₂/M phase arrest, Apoptosis, transient integrated stress response, upregulation of ATF4, and phosphorylation of GCN2. ZNL-02-096 reduces Tyr15 phosphorylation of CDK1. ZNL-02-096 can be used in research related to ovarian cancer, acute lymphoblastic leukemia, triple-negative breast cancer, multiple myeloma, and pancreatic ductal adenocarcinoma.

GSK461364 analogue 1 is a thiophene-based PLK1 inhibitor with a PLK1 IC₅₀ of 2 nM and a PLK3 IC₅₀ of 630 nM. GSK461364 analogue 1 also acts as an inhibitor of Nek2 kinase (IC₅₀: 21 nM). GSK461364 analogue 1 has a solubility of ≥190 μM in pH 7.4 PBS and a human plasma protein binding rate of 91.5%. GSK461364 analogue 1 can be used in studies related to colon cancer, lung cancer, breast cancer and ovarian cancer.

ON1231320 is a highly specific polo like kinase 2 (PLK2) inhibitor with an IC₅₀ of 0.31 μM. ON1231320 blocks tumor cell cycle progression in the G2/M phase in mitosis, causing apoptotic cell death. ON1231320, an arylsulfonyl pyrido-pyrimidinone, has antitumor activity.

TAK-960 is an orally available, selective inhibitor of polo-like kinase 1 (PLK1), with an IC₅₀ of 0.8 nM. TAK-960 also shows inhibitory activities against PLK2 and PLK3, with IC₅₀s of 16.9 and 50.2 nM, respectively. TAK-960 inhibits proliferation of multiple cancer cell lines and exhibits significant efficacy against multiple tumor xenografts.

HMN-214, an orally bioavailable proagent of HMN-176, is an inhibitor of polo-like kinase-1 (plk1), with antitumor activity.

GW843682X is a selective, ATP-competitive inhibitor of PLK1 and PLK3, with IC₅₀s of 2.2 nM and 9.1 nM, respectively, and is also >100-fold selective against ～30 other kinases.

Ro3280 is a potent, highly selective inhibitor of PLK1 with an IC₅₀ and a K_d of 3 nM and 0.09 nM, respectively, and nearly has no effect on PLK2 and PLK3.

MLN0905 is a potent, orally active Polo-like kinase 1 (PLK1) inhibitor. MLN0905 has inhibitory potency against PLK1 with an IC₅₀ value of 2 nM. MLN0905 can be used for the research of cancer.

Rigosertib sodium (ON-01910 sodium) is a multi-kinase inhibitor and a selective anti-cancer agent, which induces apoptosis by inhibition the PI3K/Akt pathway, promotes the phosphorylation of histone H2AX and induces G2/M arrest in cell cycle. Rigosertib sodium is a selective and non-ATP-competitive inhibitor of PLK1 with an IC₅₀ of 9 nM.

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.

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).