HA14-1

Catalog No.S1071 Batch:S107103

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Technical Data

Formula

C17H17BrN2O5
Molecular Weight 409.23 CAS No. 65673-63-4
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description HA14-1 is a non-peptidic ligand of a Bcl-2 surface pocket with IC50 of ~9 μM.
Targets
Bcl-2 [1]
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]

Protocol (from reference)

Kinase Assay:

[1]
  • Affinity determination

    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.

Cell Assay:

[2]
  • Cell lines

    HF1A3, HF4.9 and HF28RA cells

  • Concentrations

    ~25 μM

  • Incubation Time

    20 h

  • Method

    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
Animal Study:

[3]
  • Animal Models

    Female Swiss nude mice bearing BeGBM xenografts.

  • Dosages

    400 nM

  • Administration

    Inject at the site of cell injection.

Customer Product Validation

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

Selleck's HA14-1 has been cited by 6 publications

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

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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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