HA14-1

Modify Date: 2024-01-08 11:47:19

HA14-1 structure	Common Name	HA14-1
	CAS Number	65673-63-4	Molecular Weight	409.231
	Density	1.5±0.1 g/cm3	Boiling Point	535.1±50.0 °C at 760 mmHg
	Molecular Formula	C₁₇H₁₇BrN₂O₅	Melting Point	105ºC
	MSDS	Chinese USA	Flash Point	277.4±30.1 °C

Use of HA14-1

HA14-1 is a Bcl-2/Bcl-XL antagonist. HA14-1 binds the designated pocket on Bcl-2 with the IC50 of ≈9 μM in competing with the Bcl-2 binding of Flu-BakBH3, and inhibits its function.

Name	ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
Synonym	More Synonyms

Description	HA14-1 is a Bcl-2/Bcl-XL antagonist. HA14-1 binds the designated pocket on Bcl-2 with the IC50 of ≈9 μM in competing with the Bcl-2 binding of Flu-BakBH3, and inhibits its function.
Related Catalog	Signaling Pathways >> Apoptosis >> Bcl-2 Family Research Areas >> Cancer
Target	Bcl-2:9 μM (IC50) Bcl-xL
In Vitro	HA14-1 is a nonpeptidic ligand of a Bcl-2 surface pocket. HA14-1 induces the activation of Apaf-1 and caspases, possibly by binding to Bcl-2 protein and inhibiting its function. The interaction of HA14-1 with the Bcl-2 surface pocket appeared to be specific for the chemical structure of HA14-1 as a series of synthetic analogs derived from HA14-1 containing various modifications are found to have widely different Bcl-2 binding activities. To examine the effect of HA14-1 on cell viability, HL-60 cells are treated with various concentrations of HA14-1 for 4 h. HA14-1 induces the death of HL-60 cells in a dose-dependent manner. At 50 μM, HA14-1 causes the lost of viability in more than 90% of the cells[1]. HA14-1 is a Bcl-2/Bcl-xL antagonist[2].
In Vivo	Swiss nude mice are challenged with BeGBM cells (104 injected s.c.). HA14-1 (400 nmol) in 100 μL free RPMI 1640-50% DMSO, or the carrier alone, is given at the site of injection once weekly from day 2 following cell injection. HA14-1 treatment does not have any significant effect on the growth of glioblastoma tumors in immunodeficient mice as monitored twice weekly by measuring the volume of the expanding tumors. Moreover, no gross organ toxicity or weight loss can be detected in mice receiving such treatment. To analyze whether HA14-1 treatment might enhance the efficiency of another antitumoral treatment, Swiss nude mice challenged with human glioblastoma multiforme cells are also given i.p. low doses of Etoposide (2.5 mg/kg in 200 μL of 0.9% NaCl 5 days a week from day 2 following cell injection) together with HA14-1 or mock treatment. Whereas Etoposide treatment is insufficient by itself to restrain the growth of glioblastoma cells, its combination with HA14-1 leads to a significant restrain on tumor growth as judged by the ability of the combined treatment to increase the doubling time of the tumor volume[3].
Kinase Assay	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-xLprotein with high-affinity (dissociation constant, KD, of ≈0.34 μM). 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 (dissociation constant, KD, of ≈0.20 μM). 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[1].
Cell Assay	The dose-dependent effect of the compounds on the viability of HL-60 cells is tested by using the CellTiter 96AQ kit. In brief, the cell suspension containing 1×105 cells in 100 μL of medium are plated into a 96-well plate and are incubated with compounds (e.g., HA14-1; 10, 20, 30, 40, 50 and 60 μM) at different concentrations. The numbers of apoptotic cells are determined by measuring the optical density on a Wallac Victor counter at 490 nm. Cell viability is also determined by Trypan blue exclusion in a hemocytometer[1].
Animal Admin	Mice[3] Six- to 7-week-old female Swiss nude mice are maintained under standard conditions for 2 weeks before their s.c. injection with 104 BeGBM cells (resuspended in 100 μL free RPMI 1640) into the hind limbs on day 0. Treatment with HA14-1 is done by injection of 400 nmol HA14-1 in 100 μL free RPMI 1640-50% DMSO at the site of cell injection. Treatment starts at day 2 and is repeated once weekly for the following 4 weeks. Control mice receive equivalent volumes of vehicle (100 μL free RPMI 1640-50% DMSO) with the same frequency. Etoposide treatment is done as follows: either Etoposide (2.5 mg/kg) or sterile physiologic saline is given i.p. to HA14-1- or mock-treated animals on days 2 and 3 followed by five injections per week during the next 4 weeks. Tumor sizes are measured with calipers by the same observer twice weekly. Tumor volumes are calculated.
References	[1]. Wang JL, et al. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7124-9. [2]. Kessel D, et al. Initiation of apoptosis and autophagy by the Bcl-2 antagonist HA14-1. Cancer Lett. 2007 May 8;249(2):294-9. [3]. Manero F, et al. The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death. Cancer Res. 2006 Mar 1;66(5):2757-64.

Density	1.5±0.1 g/cm3
Boiling Point	535.1±50.0 °C at 760 mmHg
Melting Point	105ºC
Molecular Formula	C₁₇H₁₇BrN₂O₅
Molecular Weight	409.231
Flash Point	277.4±30.1 °C
Exact Mass	408.032074
PSA	111.64000
LogP	3.70
Appearance of Characters	powder
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.574
Storage condition	−20°C
Water Solubility	DMSO: 26 mg/mL

Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
Safety Phrases	22-24/25
RIDADR	NONH for all modes of transport
WGK Germany	3
HS Code	2932209090

Ethyl cyanoacetate

CAS#:105-56-6

5-Bromosalicyla...

CAS#:1761-61-1

~99%

HA14-1

CAS#:65673-63-4

Literature: Tetrahedron Letters, , vol. 46, # 20 p. 3497 - 3499

Precursor 2
CAS#:105-56-6 Ethyl cyanoacetate CAS#:1761-61-1 5-Bromosalicyla...
DownStream 0

HS Code	2932209090
Summary	2932209090. other lactones. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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Dev. Biol. 350 , 279-89, (2011)

Morpholino antisense oligonucleotides (MOs) are widely used as a tool to achieve loss of gene function, but many have off-target effects mediated by activation of Tp53 and associated apoptosis. Here, ...

The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions.

PLoS ONE 8 , e63232, (2013)

Autophagy can be induced under nutrition stress conditions. Bcl-2 is a pro-survival protein which inhibits apoptosis and autophagy. However, the role of Bcl-2 in autophagy regulation and cell survival...

Ethyl (4R)-2-amino-6-bromo-4-[(1R)-1-cyano-2-ethoxy-2-oxoethyl]-4H-chromene-3-carboxylate

Ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate

S1071_Selleck

4H-1-Benzopyran-4-acetic acid, 2-amino-6-bromo-α-cyano-3-(ethoxycarbonyl)-, ethyl ester

HA 14-1

4H-1-Benzopyran-4-acetic acid, 2-amino-6-bromo-α-cyano-3-(ethoxycarbonyl)-, ethyl ester, (αR,4R)-

HA14-1

DC Chemicals Limited
China
Product Name: HA14-1
Price: $400.0/100mg $800.0/250mg $1600.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

Dayang Chem (Hangzhou) Co., Ltd.
China
Product Name: HA14-1
Price: $Inquiry/100g $Inquiry/1kg $Inquiry/100kg $Inquiry/1000kg
Purity: 98.0%
Stocking Period: Inquiry
Contact: Ms Wang

Zhejiang Hangyu API Co., Ltd
China
Product Name: HA14-1
Price: ￥Inquiry/1kg
Purity: 99.5%
Stocking Period: Inquiry
Contact: Vinnie

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