SB743921 HCl

製品コードS2182 バッチS218201

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	C₃₁H₃₃N₂O₃.HCl
	分子量	553.52	CAS No.	940929-33-9
Solubility (25°C)*	体外	DMSO	111 mg/mL (200.53 mM)
		Ethanol	111 mg/mL (200.53 mM)
		Water	22 mg/mL (39.74 mM)
* <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	SB743921 is a kinesin spindle protein (KSP) inhibitor with K_i of 0.1 nM, almost no affinity to MKLP1, Kin2, Kif1A, Kif15, KHC, Kif4 and CENP-E. Phase 1/2.
in vitro	The K_i of SB 743921 for human and mouse KSP is 0.1 nM and 0.12 nM, respectively, while the K_i of SB 743921 for other kinesins including MKLP1, Kin2 is more than 70 μM. SB 743921 blocks assembly of a functional mitotic spindle, thereby causing cell cycle arrest in mitosis and subsequent cell death. SB-743921 has improved potency over ispinesib in both biochemical and cellular assays. ^[1]
in vivo	SB-743921 is greater efficacy in vivo against P388 leukemia. SB-743921 has significant efficacy in a broad spectrum of tumor models differing from that of taxanes. SB-743921 is shown to have activity against advanced human tumor xenografts Colo205 (complete regressions), MCF-7, SK-MES, H69, OVCAR-3 (complete and partial regressions), and HT-29, MX-1, MDA-MB-231, A2780 (tumor growth delay). SB-743921 doesn't cause the neuropathy often associated with the tubulin agents. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Biochemistry assay
キナーゼアッセイ	The motor domains of KSP (amino acids 1–360) is expressed as in Escherichia coli BL21(DE3) as COOH-terminal 6-his fusion proteins. Bacterial pellets are lysed in a microfluidizer with a lysis buffer [50 mM Tris-HCl; 50 mM KCl, 10 mM imidazole, 2 mM MgCl₂, 8 mM β-mercaptoethanol, 0.1 mM ATP (pH 7.4)], and proteins are purified using Ni-NTA agarose affinity chromatography, with an elution buffer consisting of 50 mM PIPES, 10% sucrose, 300 mM imidazole, 50 mM KCl, 2 mM MgCl₂, mM β-mercaptoethanol, and 0.1 mM ATP (pH 6.8). Steady-state measurements of ATPase activity are performed with a pyruvate kinase–lactate dehydrogenase detection system that coupled the appearance of ADP with oxidation of NADH. Absorbance changes are monitored at 340 nm. All biochemical experiments are performed in PEM25 buffer [25 mM Pipes/KOH (pH 6.8), 2 mM MgCl₂, 1 mM EGTA] supplemented with 10 μM SB 743921 for experiments involving microtubules. Rates of ADP release are measured in a stopped-flow apparatus; the decrease in fluorescence of MANT-ATP is monitored. Rates of Pi release are measured in a stopped-flow apparatus, using bacterial phosphate binding protein modified with 7-diethylamino-3-((((2 maleimidyl)ethyl)amino)carbonyl)coumarin (MDCC) dye. K_i estimates of KSP inhibitors are extracted from the dose–response curves, with explicit correction for enzyme concentration. Tubulin polymerization by measuring changes in absorbance at 340 nm is monitored. The assay is performed in 100-μL volumes in 96-well half-area microtiter plates, using a microplate reader with the incubation temperature set at 37 °C.
細胞アッセイ	細胞株	HeLa cells
	濃度	~1 μM
	反応時間	24 hours
	実験の流れ	All cells including HeLa cells are cultured in 10% FCS in RPMI 1640 in 5% CO₂. We assessed 48-hour growth inhibition by serial dilution of SB 743921 relative to DMSO-treated cells in 96-well microtiter plates, using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium. Cell growth is represented as the ratio of absorbance of treated cells to DMSO control, plotted by concentration and fitted to a four-parameter curve. Concentrations at which cellular growth is inhibited by 50% are extrapolated from the curve fit. The DNA content of HeLa cells cultured in the presence or absence of 1 μM SB 743921 for 24 hours is assessed by propidium iodide staining and flow cytometry. Immunofluorescence images are collected of HeLa cells treated for 24 hours with 1 μM SB 743921, fixed with 2% formaldehyde, permeabilized, and stained with DM1-α, anti-γ-tubulin, and 1 μg/mL 4′,6-diamidino-2-phenylindole, and with Alexa 488 secondary goat antirabbit IgG and Rhodamine-X goat antimouse IgG. Images are collected with a DeltaVision Restoration Microscopy System at a magnification of ×600. Z stacks (0.2 μm) are collected, and out of focus information is removed by constrained iterative deconvolution. Z stacks are then compressed into to a single image plane.
動物実験	動物モデル	Female BDF1 mice with P388 lymphocytic leukemia cells
	投薬量	7.5 mg/kg- 30 mg/kg
	投与方法	Administered via i.p.

参考

カスタマーフィードバック

: Data from [Mol Oncol, 2014, 8(8):1404-18]

: Data from [Data independently produced by Leuk Lymphoma, 2014, 1-8]

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：

Dual inhibition of KIF11 and BCL2L1 induces apoptosis in lung adenocarcinoma cells [ Biochem Biophys Res Commun, 2023, 678:84-89]	PubMed: 37619315
Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity [ Cancer Cell, 2022, 40(7):754-767.e6]	PubMed: 35820397
The therapeutic effect of KSP inhibitors in preclinical models of cholangiocarcinoma [ Cell Death Dis, 2022, 13-9:799]	PubMed: 36123339
Kinesin spindle protein inhibitor exacerbates cisplatin-induced hair cell damage [ Arch Biochem Biophys, 2022, 731:109432]	PubMed: 36273620
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19]	PubMed: 32645325
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19]	PubMed: 32645325
Therapeutic targeting of KSP in preclinical models of high-risk neuroblastoma [ Sci Transl Med, 2020, 12(562)eaba4434]	PubMed: 32967973
Mitochondria Redistribution in Enterovirus A71 Infected Cells and Its Effect on Virus Replication [ Virol Sin, 2019, 34(4):397-411]	PubMed: 31069716
High kinesin family member 11 expression predicts poor prognosis in patients with clear cell renal cell carcinoma [ J Clin Pathol, 2019, 72(5):354-362]	PubMed: 30819726
Meiotic arrest and spindle defects are associated with altered KIF11 expression in porcine oocytes. [ Environ Mol Mutagen, 2018, 59(9):805-812]	PubMed: 30151839

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。

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