HA14-1

製品コードS1071 バッチS107101

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	C₁₇H₁₇BrN₂O₅
	分子量	409.23	CAS No.	65673-63-4
Solubility (25°C)*	体外	DMSO	82 mg/mL (200.37 mM)
		Ethanol	82 mg/mL (200.37 mM)
		Water	Insoluble
* <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	HA14-1 is a non-peptidic ligand of a Bcl-2 surface pocket with IC50 of ~9 μM.
in vitro	HA14-1 is a small molecule and nonpeptidic ligand of a Bcl-2 surface pocket with IC50 of approximately 9 μM. HA14-1 induces the apoptosis of HL-60 cells in a dose-dependent manner via caspase activation. ^[1] HA14-1 shows cytotoxic effects on HF1A3, HF4.9 and HF28RA follicular lymphoma B cell lines with LC50 of 4.5 μM, 12.6 μM and 8.1 μM respectively. HA14-1 induces apoptosis of HF1A3, HF4.9 and HF28RA cells via caspase and ROS. ^[2]
in vivo	HA14-1(400 nM) treatment did not have any significant effect on the growth of glioblastoma tumors in immunodeficient mice. But HA14-1 (400 nM) increases the effect of the DNA-damaging agent etoposide (2.5 mg/Kg) on glioblastoma growth in vivo. ^[3]

プロトコル(参考用のみ)

キナーゼアッセイ	Affinity determination
キナーゼアッセイ	The binding affinity of organic compounds to Bcl-2 protein in vitro is determined by a competitive binding assay based on fluorescence polarization. For this assay, 5-carboxyfluorecein is coupled to the N terminus of a peptide, GQVGRQLAIIGDDINR, derived from the BH3 domain of Bak (Flu-BakBH3), which has been shown to bind to the surface pocket of the Bcl-xL protein with high-affinity. According to our molecular modeling studies and binding measurement using fluorescence polarization, the Flu-BakBH3 peptide binds the surface pocket of Bcl-2 with a similar affinity. Bcl-2 used in this assay is a recombinant GST-fused soluble protein. Flu-BakBH3 and Bcl-2 protein are mixed in the presence or absence of organic compounds under standard buffer conditions and are incubated for 30 min. The binding of Flu-BakBH3 to Bcl-2 protein is measured on a LS-50 luminescence spectrometer equipped with polarizers using a dual path length quartz cell (500 μl). The fluorophore is excited with vertical polarized light at 480 nm (excitation slit width 15 nm), and the polarization value of the emitted light is observed through vertical and horizontal polarizers at 530 nm (emission slit width 15 nm). The binding affinity of each compound for Bcl-2 protein is assessed by determining the ability of different concentrations of the compound to inhibit Flu-BakBH3 binding to Bcl-2.
細胞アッセイ	細胞株	HF1A3, HF4.9 and HF28RA cells
	濃度	~25 μM
	反応時間	20 h
	実験の流れ	The cytotoxic effects of HA14-1 against different FL cell lines are determined by the MTT assay. Briefly, the cells (5000/well) are incubated in triplicate in 96-well plate in the presence or absence of HA14-1 for 20 h at 37 °C. Thereafter, the MTT solution is added to each well. After 4 h incubation at 37 °C, the optical density (OD) is measured by means of 96-well plate reader, with the extraction buffer as a blank. The following formula is used: percentage cell viability = (OD of the experiment samples/OD of the control) × 100. Sigmoidal dose-response curves are fitted to the mean cell viability plotted against log HA14-1 dose and lethal concentration 50% (LC50) values are calculated from the resulting curves using Prism 4.0 softw
動物実験	動物モデル	Female Swiss nude mice bearing BeGBM xenografts.
	投薬量	400 nM
	投与方法	Inject at the site of cell injection.

参考

カスタマーフィードバック

: Data from [Cancer Res, 2011, 71(13), 4494-505]

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：

Comparison of putative BH3 mimetics AT-101, HA14-1, sabutoclax and TW-37 with ABT-737 in platelets. [ Platelets, 2020, 10.1080/09537104.2020.1724276]	PubMed: 32079453
Antiapoptotic BCL-2 proteins determine sorafenib/regorafenib resistance and BH3-mimetic efficacy in hepatocellular carcinoma. [ Oncotarget, 2018, 9(24):16701-16717]	PubMed: 29682179
Pharmacological inhibition of Bcl-xL sensitizes osteosarcoma to doxorubicin. [Baranski Z, et al. Oncotarget, 2015, 6(34):36113-25]	PubMed: 26416351
Lack of GCN5 remarkably enhances the resistance against prolonged endoplasmic reticulum stress-induced apoptosis through up-regulation of Bcl-2 gene expression [Kikuchi H, et al. Biochem Biophys Res Commun, 2015, 463(4):870-5]	PubMed: 26086109
BH3 Mimetics Demonstrate Differential Activities Dependent Upon the Functional Repertoire of Pro- and Anti-Apoptotic BCL-3 Family Proteins [Renault TT, et al. J Biol Chem, 2014, 289(38):26481-91]	PubMed: 25096574
MET-independent lung cancer cells evading EGFR kinase inhibitors are therapeutically susceptible to BH3 mimetic agents [Fan W Cancer Res, 2011, 71(13):4494-505]	PubMed: 21555370

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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