GSK923295

Catalog No.S7090 Batch:S709001

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Technical Data

Formula

C32H38ClN5O4
Molecular Weight 592.13 CAS No. 1088965-37-0
Solubility (25°C)* In vitro DMSO 100 mg/mL (168.88 mM)
Ethanol 100 mg/mL (168.88 mM)
Water Insoluble
In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 5.000mg/ml (8.44mM) Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 0.625mg/ml (1.06mM) Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description GSK923295 is a first-in-class, specific allosteric inhibitor of CENP-E kinesin motor ATPase with Ki of 3.2 nM, and less potent to mutant I182 and T183. This compound induces post-mitotic apoptosis. Phase 1.
Targets
CENP-E
(Cell-free assay)
3.2 nM(Ki)
In vitro

GSK923295 is the first potent and selective inhibitor of the mitotic kinesin centromere-associated protein-E (CENP-E). This compound is uncompetitive with both ATP and microtubules (MT), inhibiting CENP-E MT-stimulated ATPase activity with a Ki of 3.2 nM, highly selective over other kinesins. It inhibits release of inorganic phosphate and stabilises CENP-E motor domain interaction with microtubules, reduces the rate of ATP-promoted dissociation of CENP-E from MT (koff, MT) by more than 50-fold. This chemical causes failure of metaphase chromosome alignment and induces mitotic arrest. It is a potent inhibitor of tumour cell growth, with an average GI50 of 253 nM and a median GI50 of 32 nM for 237 tumour cell lines. This compound inhibits tumour cell growth more effectively when mitogen-activated protein kinase (MEK/ERK) signalling is also inhibited.

In Vivo

GSK923295 produces clear increases in the abundance of mitotic figures and scattered apoptotic bodies in tumours. This compound causes a dose-dependent increase in the ratio of 4n to 2n nuclei. It exhibits robust, dose-dependent antitumour activity against Colo205 xenografts, including partial and complete regressions at the 125 mg/kg dose. It demonstrates significant antitumour activity against solid tumour models, inducing CRs in Ewing sarcoma, rhabdoid, and rhabdomyosarcoma xenografts, may be a valuable therapeutic target in paediatric cancer.

Features First potent, CENP-E-selective inhibitor that has been tested in Phase I clinical trials for treatment of Refractory Cancers.

Protocol (from reference)

Kinase Assay:

[1]
  • Enzymology

    Kinesin motor domains are expressed in Escherichia coli BL21(DE3) and purified. CENP-E proteins includes residues 2–340 with a carboxyl-terminal 6-his tag. All studies using MT are conducted in PEM25 buffer [25mM PipesK+ (pH 6.8), 2mM MgCl2, 1mM EGTA] . The IC50 for steady-state inhibition is determined at 500 μM ATP, 5 μM MT, and 1 nM CENP-E in PEM25 buffer.
Cell Assay:

[1]
  • Cell Lines

    Tumor cell lines

  • Concentrations

    ~10 μM

  • Incubation Time

    72 h

  • Method

    Cell-growth inhibition assays are performed by MDS in 384-well plates, and DNA content of fixed cells stained with DAPI using an Incell 1000 is analyzed. DNA content is determined 24 h after seeding (T0) and after exposure to varying concentrations of drug for an additional 72 h (T72). All T72 measurements are normalized to T0. Curves are analyzed using the XLfit curve-fitting tool to determine the concentration of this compound yielding 50% growth inhibition relative to T0 and Ymax values (GI50).
Animal Study:

[1]
  • Animal Models

    mice bearing xenografts of the Colo205 colon tumor-cell line

  • Dosages

    125 mg/kg, two cycles of three daily injections separated by 1 week

  • Administration

    i.p.

References

  • https://pubmed.ncbi.nlm.nih.gov/20167803/
  • http://pubs.acs.org/doi/ipdf/10.1021/ml900018m
  • https://pubmed.ncbi.nlm.nih.gov/21584937/
  • https://pubmed.ncbi.nlm.nih.gov/22948716/

Customer Product Validation

<p>(f) HeLa cells were treated with mitotic kinesin CENP-E inhibitor GSK923295 (50 nM) for 1 h to generate misaligned kinetochores. After fixation, cells were stained for ACA, tubulin, and TIP60. Statistical significance was tested by two-sided t-test and represented by asterisks corresponding to ***, p < 0.001. Scale bars, 5 μm.</p>

, , Nat Chem Biol, 2016, 12(4):226-32.

Sellecks GSK923295 Has Been Cited by 37 Publications

Epigenetic Heritability of Cell Plasticity Drives Cancer Drug Resistance through a One-to-Many Genotype-to-Phenotype Paradigm [ Cancer Res, 2025, 85(15):2921-2938] PubMed: 40499006
Epigenetic Heritability of Cell Plasticity Drives Cancer Drug Resistance through a One-to-Many Genotype-to-Phenotype Paradigm [ Cancer Res, 2025, 10.1158/0008-5472.CAN-25-0999] PubMed: 40499006
Small-molecule inhibition of kinesin KIF18A reveals a mitotic vulnerability enriched in chromosomally unstable cancers [ Nat Cancer, 2024, 5(1):66-84] PubMed: 38151625
Spatial control of the APC/C ensures the rapid degradation of cyclin B1 [ EMBO J, 2024, 43(19):4324-4355] PubMed: 39143240
A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset [ Curr Biol, 2024, 34(5):1133-1141.e4] PubMed: 38354735
A farnesyl-dependent structural role for CENP-E in expansion of the fibrous corona [ J Cell Biol, 2024, 223(1)e202303007] PubMed: 37934467
Simple aneuploidy evades p53 surveillance and promotes niche factor-independent growth in human intestinal organoids [ Mol Biol Cell, 2024, 35(8):br15] PubMed: 38985518
Epigenetic dysregulation from chromosomal transit in micronuclei [ Nature, 2023, 619(7968):176-183] PubMed: 37286593
Alternative CDC20 translational isoforms tune mitotic arrest duration [ Nature, 2023, 617(7959):154-161] PubMed: 37100900
Molecular landscape and functional characterization of centrosome amplification in ovarian cancer [ Nat Commun, 2023, 14(1):6505] PubMed: 37845213

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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