GSK923295

製品コードS7090 バッチS709001

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₃₂H₃₈ClN₅O₄

分子量

592.13

CAS No.

1088965-37-0

Solubility (25°C)*

体外

DMSO

100 mg/mL (168.88 mM)

Ethanol

100 mg/mL (168.88 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

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 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	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 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	GSK923295 is a first-in-class, specific allosteric inhibitor of CENP-E kinesin motor ATPase with K_i of 3.2 nM, and less potent to mutant I182 and T183. GSK923295 induces post-mitotic apoptosis. Phase 1.
in vitro	GSK923295 is the first potent and selective inhibitor of the mitotic kinesin centromere-associated protein-E (CENP-E). ^[1]^[2] This compound is uncompetitive with both ATP and microtubules (MT), inhibiting CENP-E MT-stimulated ATPase activity with a K_i of 3.2 nM, highly selective over other kinesins. It inhibits release of inorganic phosphate and stabilizes CENP-E motor domain interaction with microtubules, reduces the rate of ATP-promoted dissociation of CENP-E from MT (k_{off, MT}) by more than 50-fold. This chemical causes failure of metaphase chromosome alignment and induces mitotic arrest. It is a potent inhibitor of tumor cell growth, with an average GI50 of 253 nM and a median GI50 of 32 nM for 237 tumor cell lines. ^[1] This compound inhibits tumor cell growth more effectively when mitogen-activated protein kinase (MEK/ERK) signaling is also inhibited. ^[4]
in vivo	GSK923295 produces clear increases in the abundance of mitotic figures and scattered apoptotic bodies in tumors. This compound causes a dose-dependent increase in the ratio of 4n to 2n nuclei. It exhibits robust, dose-dependent antitumor activity against Colo205 xenografts, including partial and complete regressions at the 125 mg/kg dose.^[1] It demonstrates significant antitumor activity against solid tumor models, inducing CRs in Ewing sarcoma, rhabdoid, and rhabdomyosarcoma xenografts, may be a valuable therapeutic target in pediatric cancer. ^[3]
特徴	First potent, CENP-E-selective inhibitor that has been tested in Phase I clinical trials for treatment of Refractory Cancers.

プロトコル(参考用のみ)

キナーゼアッセイ	Enzymology
キナーゼアッセイ	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.
細胞アッセイ	細胞株	Tumor cell lines
	濃度	~10 μM
	反応時間	72 h
	実験の流れ	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 Y_max values (GI50).
動物実験	動物モデル	mice bearing xenografts of the Colo205 colon tumor-cell line
	投薬量	125 mg/kg, two cycles of three daily injections separated by 1 week
	投与方法	i.p.

参考

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/

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カスタマーフィードバック

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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 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
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
Epigenetic dysregulation from chromosomal transit in micronuclei [ Nature, 2023, 619(7968):176-183]	PubMed: 37286593

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。