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| Targets |
Plogosertib targets polo-like kinase 1 (PLK1), a serine/threonine kinase that plays a critical role in cell cycle progression, particularly during mitosis. PLK1 is involved in centrosome maturation, spindle formation, and cytokinesis. It is overexpressed in many cancers and is associated with poor prognosis. By inhibiting PLK1 with IC50 = 3 nM, Plogosertib disrupts mitosis and induces cell death in cancer cells. It also inhibits PLK2 (IC50: 149 nM) and PLK3 (IC50: 393 nM).
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| ln Vitro |
Plogosertib (CYC140) is >50-fold more powerful against PLK2 and PLK3 (IC50: 149 nM and 393 nM, respectively) and specifically inhibits PLK1 (IC50: 3 nM) [2]. The PLK1 substrate pSer4-nucleophosmin (p-NPM) is phosphorylated less in KYSE-410 cells when plogosertib (0–4 μM) is administered for two hours [2]. In HeLa cells, plogosertib (100 nM, 24 hours) increases the fraction of mitotic cells and unipolar spindles [2]. Plogosertib (72 h) is less harmful to non-malignant cell lines (IC50: 82 nM) and preferentially suppresses the growth of malignant cell lines (IC50: 14-21 nM) [2].
In vitro, Plogosertib inhibits PLK1 with IC50 = 3 nM and is >50-fold more potent against PLK1 than PLK2 (149 nM) and PLK3 (393 nM). It has antiproliferative and anti-cancer activity. These in vitro activities make Plogosertib a promising candidate for cancer research and development. |
| ln Vivo |
Preclinical xenograft models of acute leukemia and solid tumors show growth inhibition in response to Plogosertib (CYC140; oral, 40 mg/kg, 5/2/5 daily) [2]. The pharmacokinetic parameters of plogosertib (Compound A7, 1 mg/kg, mouse) are as follows: Cmax (453 ng/mL), AUC (377 hr·ng/mL), and Cl (2445 mL/h/kg)[3].
In vivo studies with Plogosertib are limited. As a PLK1 inhibitor, the compound has potential for cancer treatment. Specific in vivo efficacy data are not extensively documented. The compound is being studied for cancer research applications. |
| Enzyme Assay |
In vitro kinase assays are used to characterize Plogosertib's inhibition of PLK1, PLK2, and PLK3. Kinases are incubated with the compound and ATP substrate, and kinase activity is measured by phosphorylation of a peptide substrate. IC50 values of 3 nM (PLK1), 149 nM (PLK2), and 393 nM (PLK3) are determined.
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| Cell Assay |
Cell proliferation assay [2]
Cell Types: KYSE-410 Cell Tested Concentrations: 0, 0.07, 0.15, 0.3, 0.6, 1.25 μM Incubation Duration: 72 h Experimental Results: Inhibition of cell proliferation in a concentration-dependent manner. Western Blot Analysis[2] Cell Types: KYSE-410 Cell Tested Concentrations: 0, 0.01, 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2, 4 μM Incubation Duration: 2 hrs (hours) (p-NPM), 24 hrs (hours) (p -NPM) -HH3), 72 hrs (hours) (cPARP) Experimental Results: diminished phosphorylation of PLK1 substrate (p-NPM). Increased cleavage of mitotic markers pSer10 histone H3 (p-HH3) and PARP (cPARP, an indicator of cell death). Cell-based assays for Plogosertib are conducted in cancer cell lines. Cells are treated with the compound at various concentrations, and cell viability, proliferation, and apoptosis are assessed. Cell cycle analysis is performed by flow cytometry to evaluate mitotic arrest. These assays characterize the compound's anti-cancer activity. |
| Animal Protocol |
Animal/Disease Models: HL60 promyelocytic leukemia xenograft [2]
Doses: 40, 54, 67 mg/kg, 5/2/5 daily Route of Administration: Oral Experimental Results: Inhibition of tumor growth (>87%), and body weight Not Dramatically diminished. Animal/Disease Models: OE19 esophageal xenograft [2] Doses: 40 mg/kg, 5/2 daily Route of Administration: Oral Experimental Results:Inhibition of tumor growth (61% inhibition). In vivo animal experiments with Plogosertib are conducted in xenograft models. The compound is administered, and tumor growth inhibition is assessed. PLK1 inhibition and downstream signaling are evaluated in tumor tissues. Specific protocols are not extensively documented. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Plogosertib have not been extensively characterized. The compound has molecular weight 616.80 and molecular formula C34H48N8O3. Solubility: DMSO 100 mg/mL. Storage: appropriately. Specific PK parameters such as half-life, Cmax, and bioavailability have not been reported.
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| Toxicity/Toxicokinetics |
Safety and toxicology data for Plogosertib are limited. The compound is for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling the compound. The compound should be stored properly and disposed of in accordance with applicable regulations.
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| References | |
| Additional Infomation |
Plogosertib is a competitive inhibitor that inhibits the binding of adenosine triphosphate (ATP) to polo-like kinase 1 (PLK1; PLK-1; STPK13), exhibiting potential antitumor activity. After administration, plogosertib selectively targets, binds to, and inhibits PLK1, thereby interfering with mitosis and inducing selective G2/M phase cell cycle arrest in PLK1-overexpressing tumor cells, ultimately leading to apoptosis. PLK1, named after the Drosophila polo gene, is a serine/threonine kinase crucial for the regulation of mitosis and plays a key role in tumor cell proliferation, transformation, and invasion. PLK1 expression is upregulated in various tumor cell types, and high expression is associated with increased tumor invasiveness and poor prognosis.
Plogosertib has CAS number 1137212-79-3, molecular formula C34H48N8O3, and molecular weight 616.80. Synonyms: CYC140. It is a potent PLK1 inhibitor with IC50 = 3 nM, and also inhibits PLK2 (149 nM) and PLK3 (393 nM). It has antiproliferative and anti-cancer activity. Purity: ≥98%. Not for human use; for research purposes only. |
| Molecular Formula |
C34H48N8O3
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| Molecular Weight |
616.796727180481
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| Exact Mass |
616.384
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| CAS # |
1137212-79-3
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| PubChem CID |
42640739
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
45
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| Complexity |
1040
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1N(C2=CN=C(NC3C=CC(C(=O)N[C@H]4CC[C@H](N5CCN(C)CC5)CC4)=CC=3OC)N=C2N(C2CCCC2)CC21CC2)C
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| InChi Key |
UFNLNMWVOMFWGS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C34H48N8O3/c1-39-16-18-41(19-17-39)25-11-9-24(10-12-25)36-31(43)23-8-13-27(29(20-23)45-3)37-33-35-21-28-30(38-33)42(26-6-4-5-7-26)22-34(14-15-34)32(44)40(28)2/h8,13,20-21,24-26H,4-7,9-12,14-19,22H2,1-3H3,(H,36,43)(H,35,37,38)
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| Chemical Name |
4-[(9-cyclopentyl-5-methyl-6-oxospiro[8H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropane]-2-yl)amino]-3-methoxy-N-[4-(4-methylpiperazin-1-yl)cyclohexyl]benzamide
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| Synonyms |
CYC-140; CYC140; CYC 140
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~162.1 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6213 mL | 8.1064 mL | 16.2127 mL | |
| 5 mM | 0.3243 mL | 1.6213 mL | 3.2425 mL | |
| 10 mM | 0.1621 mL | 0.8106 mL | 1.6213 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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