Volasertib (BI 6727)

Alias: BI6727; BI 6727; BI-6727; Volasertib
Cat No.:V1574 Purity: ≥98%
Volasertib (formerly also known as BI6727, BI-6727, BI 6727) is a novel and highly potent dihydropteridinone-based Plk1 (polo-like kinase 1) inhibitor with potential antineoplastic activity.
Volasertib (BI 6727) Chemical Structure CAS No.: 755038-65-4
Product category: PLK
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
100mg
250mg
500mg
Other Sizes

Other Forms of Volasertib (BI 6727):

Official Supplier of:
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Volasertib (formerly also known as BI6727, BI-6727, BI 6727) is a novel and highly potent dihydropteridinone-based Plk1 (polo-like kinase 1) inhibitor with potential antineoplastic activity. In a test without cells, it inhibits Plk1 with an IC50 of 0.87 nM. Comparing volasertib to Plk2 and Plk3, the drug exhibits 6- and 65-fold higher selectivity. BI 6727 selectively inhibits Plk1, causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells, and selective G2/M arrest followed by apoptosis in a variety of tumor cells. With unique properties, BI 6727 is a highly potent and selective dihydropteridinone (enzyme IC50 = 0.87 nmol/L, EC50 = 11-37 nmol/L on a panel of cancer cell lines).

Biological Activity I Assay Protocols (From Reference)
Targets
PLK1 (IC50 = 0.87 nM); PLK2 (IC50 = 5 nM); PLK3 (IC50 = 56 nM)
ln Vitro

BI6727 belongs to the dihydropteridinone class of compounds, just like BI2536. It is an ATP-competitive kinase inhibitor. With an IC50 of 5 nM and 56 nM, respectively, BI6727 potently inhibits two closely related kinases in addition to Plk1. These are Plk2 and Plk3. Over fifty different kinases show no inhibitory activity from BI6727 at concentrations as high as 10 μM. With an EC50 of 23 nM, 21 nM, 11 nM, 15 nM, 32 nM, 36 nM, and 37 nM, respectively, BI6727 inhibits the proliferation of multiple cell lines derived from different cancer tissues, including HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji cells. In NCI-H460 cells, treatment with BI6727 (100 nM) results in an accumulation of mitotic cells with monopolar spindles and positive staining for histone H3 phosphoserine 10, indicating that cells are arrested early in the M phase and subsequently apoptosis is induced.[1] While only micromolar concentrations of BI6727 are cytotoxic for normal pediatric neural stem cells, low nanomolar concentrations of the compound exhibit strong inhibitory activity against neuroblastoma (NB) tumor-initiating cells (NB TIC) with an EC50 of 21 nM.[2] Like BI 2536, BI6727 causes the growth arrest of Daoy and ONS-76 medulloblastoma cells.[3]

ln Vivo
BI6727 administration significantly inhibits the growth of several human carcinoma xenografts, including taxane-resistant CXB1 colon carcinoma, NCI-H460, and HCT116. This growth inhibition is accompanied by an increase in both apoptosis and the mitotic index.[1] BI6727 has a superior pharmacokinetic profile and lower toxicity than BI2536 in in vivo studies.[3]
Enzyme Assay
Human Plk1 recombinant (residues 1–603) is purified by affinity chromatography employing glutathione-agarose after being expressed as an NH2-terminal, GST-tagged fusion protein using a baculoviral expression system. Using 10 μg of bovine milk casein as the substrate and 20 ng of recombinant kinase, Plk1 enzyme activity assays are conducted in the presence of serially diluted BI6727. 15 mM MgCl2, 25 mM MOPS (pH 7.0), 1 mM DTT, 1% DMSO, 7.5 μM ATP, and 0.3 μCi γ-32P-ATP are the ingredients for kinase reactions, which are carried out in a final volume of 60 μL for 45 minutes at 30 °C. When 125 μL of ice-cold 5% TCA is added, the reaction is stopped. Radiometric quantification is performed on MultiScreen mixed ester cellulose filter plates following the transfer of precipitates, followed by a 1% TCA wash. The IC50 value is computed using dose-response curves.
Cell Assay
In assays for cell proliferation, different concentrations of BI6727 are added to cells and incubated for 24, 48, and 72 hours. The growth of the cells is evaluated by measuring the conversion of Alamar blue dye in a fluorescence spectrophotometer. From the dose-response curve fit, effective concentrations (EC50) at which cellular growth is inhibited by 50% are extrapolated. Cell suspensions are fixed in 80% ethanol, treated with 0.25% Triton X-100 in PBS for 5 minutes, and then incubated for 20 minutes at room temperature with 0.1% RNase and 10 μg/mL propidium iodide in PBS. Flow cytometric analysis is used to determine cell cycle profiles.
Animal Protocol
Female BomTac:NMRI-Foxn1nu mice grafted s.c. with HCT116, NCI-H460, or CXB1 cells
~25 mg/kg/day
Injected i.v., or given intragastrally via gavage needle
References

[1]. Clin Cancer Res . 2009 May 1;15(9):3094-102.

[2]. Cancer Res . 2011 Feb 15;71(4):1385-95.

[3]. BMC Cancer . 2012 Mar 5:12:80.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C34H50N8O3
Molecular Weight
618.81
Exact Mass
618.40
Elemental Analysis
C, 65.99; H, 8.14; N, 18.11; O, 7.76
CAS #
755038-65-4
Appearance
White to off-white solid powder
SMILES
CC[C@@H]1C(=O)N(C2=CN=C(N=C2N1C(C)C)NC3=C(C=C(C=C3)C(=O)NC4CCC(CC4)N5CCN(CC5)CC6CC6)OC)C
InChi Key
SXNJFOWDRLKDSF-XKHVUIRMSA-N
InChi Code
InChI=1S/C34H50N8O3/c1-6-28-33(44)39(4)29-20-35-34(38-31(29)42(28)22(2)3)37-27-14-9-24(19-30(27)45-5)32(43)36-25-10-12-26(13-11-25)41-17-15-40(16-18-41)21-23-7-8-23/h9,14,19-20,22-23,25-26,28H,6-8,10-13,15-18,21H2,1-5H3,(H,36,43)(H,35,37,38)/t25?,26?,28-/m1/s1
Chemical Name
N-[4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-4-[[(7R)-7-ethyl-5-methyl-6-oxo-8-propan-2-yl-7H-pteridin-2-yl]amino]-3-methoxybenzamide
Synonyms
BI6727; BI 6727; BI-6727; Volasertib
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

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: ~20 mg/mL (~32.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
4%DMSO+Corn oil: 2 mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.6160 mL 8.0800 mL 16.1600 mL
5 mM 0.3232 mL 1.6160 mL 3.2320 mL
10 mM 0.1616 mL 0.8080 mL 1.6160 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

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
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?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • 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:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
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.)
+
+
+

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.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01772563 Completed Drug: volasertib
Drug: itraconazole
Neoplasms Boehringer Ingelheim February 4, 2013 Phase 1
NCT01662505 Completed Drug: Volasertib Leukemia, Myeloid, Acute Boehringer Ingelheim August 2012 Phase 1
NCT02201329 Completed Drug: Azacitidine
Drug: Volasertib
Myelodysplastic Syndromes
Leukemia, Myelomonocytic, Chronic
Boehringer Ingelheim August 2014 Phase 1
NCT00969553 Completed Drug: BI 6727 Neoplasms Boehringer Ingelheim August 2009 Phase 1
NCT01145885 Completed Drug: BI 6727 Neoplasms Boehringer Ingelheim June 2010 Phase 1
Biological Data
  • Volasertib (BI 6727)


    Volasertib inhibits the growth of cervical cancer cellsin vitro.2015 Nov 15;5(12):3548-59.

  • Volasertib (BI 6727)


    Volasertib induces cell cycle arrest at G2/M Phase in cervical cancer cells.2015 Nov 15;5(12):3548-59.

  • Volasertib (BI 6727)


    Volasertib induces apoptosis in cervical cancer cells.2015 Nov 15;5(12):3548-59.

  • Volasertib (BI 6727)


    Volasertib induces ROS accumulation in cervical cancer cells.

    Volasertib (BI 6727)

    Volasertib potentiates the activity of cisplatin to inhibit the growth of cervical cancer cellsin vitro.2015 Nov 15;5(12):3548-59.

  • Volasertib (BI 6727)


    Inhibition of ROS partially rescues volasertib-induces apoptosis in cervical cancer cells.2015 Nov 15;5(12):3548-59.

  • Volasertib (BI 6727)


    Volasertib potentiates the activity of cisplatin to inhibit xenograft tumor growth of cervical cancer cells in nude mice.2015 Nov 15;5(12):3548-59.

Contact Us