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Plogosertib

Cat No.:V44025 Purity: ≥98%
Plogosertib (CYC140) is a selective, orally bioactive ATP-competitive PLK1 inhibitor (IC50= 3 nM).
Plogosertib
Plogosertib Chemical Structure CAS No.: 1137212-79-3
Product category: New3
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
1mg
5mg
Other Sizes
Official Supplier of:
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Product Description
Plogosertib (CYC140) is a selective, orally bioactive ATP-competitive PLK1 inhibitor (IC50= 3 nM). Plogosertib is an anti-cancer compound with antiproliferation activity that is being studied in a variety of tumors like esophageal cancer, gastric cancer, leukemia, non-small cell lung cancer, ovarian cancer, and squamous cell carcinoma.
Biological Activity I Assay Protocols (From Reference)
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].
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].
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).
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).
References

[1]. Abstract 4178: The novel PLK1 inhibitor, CYC140: Identification of pharmacodynamic markers, sensitive target indications and potential combinations. Cancer Res (2017) 77 (13_Supplement): 4178.

[2]. Therapeutic potential of novel PLK1 inhibitor CYC140 in esophageal cancer and acute leukemia. European Journal of Cancer, 2016, 1(69): S117.

[3]. Treatment of proliferative diseases with pyrimidodiazepinones. Patent US20150320762A1.

Additional Infomation
Plogosertib is a competitive inhibitor for adenosine triphosphate (ATP) binding to polo-like kinase 1 (PLK1; PLK-1; STPK13), with potential antineoplastic activity. Upon administration, plogosertib selectively targets, binds to and inhibits PLK1, which disrupts mitosis and induces selective G2/M cell-cycle arrest followed by apoptosis in PLK1-overexpressing tumor cells. PLK1, named after the polo gene of Drosophila melanogaster, is a serine/threonine kinase that is crucial for the regulation of mitosis, and plays a key role in tumor cell proliferation, transformation and invasion. PLK1 expression is upregulated in a variety of tumor cell types and high expression is associated with increased aggressiveness and poor prognosis.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C34H48N8O3
Molecular Weight
616.796727180481
Exact Mass
616.384
CAS #
1137212-79-3
PubChem CID
42640739
Appearance
White to off-white solid powder
LogP
3.6
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
9
Rotatable Bond Count
7
Heavy Atom Count
45
Complexity
1040
Defined Atom Stereocenter Count
0
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
InChi Key
UFNLNMWVOMFWGS-UHFFFAOYSA-N
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)
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
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO : ~100 mg/mL (~162.13 mM)
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.

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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.
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 corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
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.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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