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A-395 

Cat. No.: HY-101512 Purity: 99.12% ee.: 99.91%
Handling Instructions

A-395 is an antagonist of polycomb repressive complex 2 (PRC2) protein-protein interactions that potently inhibits the trimeric PRC2 complex (EZH2-EED-SUZ12) with an IC50 of 18 nM.

For research use only. We do not sell to patients.

A-395 Chemical Structure

A-395 Chemical Structure

CAS No. : 2089148-72-9

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 1045 In-stock
Estimated Time of Arrival: December 31
5 mg USD 950 In-stock
Estimated Time of Arrival: December 31
10 mg USD 1700 In-stock
Estimated Time of Arrival: December 31
50 mg   Get quote  
100 mg   Get quote  

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Based on 1 publication(s) in Google Scholar

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Description

A-395 is an antagonist of polycomb repressive complex 2 (PRC2) protein-protein interactions that potently inhibits the trimeric PRC2 complex (EZH2-EED-SUZ12) with an IC50 of 18 nM.

IC50 & Target

IC50: 18 nM (Trimeric PRC2 complex)[1]

In Vitro

The embryonic ectoderm development (EED) protein is an essential subunit of Polycomb repressive complex 2 (PRC2). A-395 antagonizes of the H3K27me3 binding functions of EED. A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2. A-395 is capable of competing for H3K27me3 peptide binding to EED, with an IC50 of 7 nM. A-395, but not the close chemical analog A-395N, modulates activity of PRC2 in cells by potently reducing the H3K27 methyl mark in a highly selective manner. A-395 treatment inhibits both H3K27me2 and H3K27me3, with IC50 values of 390 nM and 90 nM, respectively. Furthermore, A-395 treatment results in growth inhibition of human tumor cell lines sensitive to SAM-competitive EZH2 inhibitors[1].

In Vivo

The embryonic ectoderm development (EED) protein is an essential subunit of Polycomb repressive complex 2 (PRC2). A-395 antagonizes of the H3K27me3 binding functions of EED. A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2. A-395 is capable of competing for H3K27me3 peptide binding to EED, with an IC50 of 7 nM. A-395, but not the close chemical analog A-395N, modulates activity of PRC2 in cells by potently reducing the H3K27 methyl mark in a highly selective manner. A-395 treatment inhibits both H3K27me2 and H3K27me3, with IC50 values of 390 nM and 90 nM, respectively. Furthermore, A-395 treatment results in growth inhibition of human tumor cell lines sensitive to SAM-competitive EZH2 inhibitors[1].

Molecular Weight

486.65

Formula

C₂₆H₃₅FN₄O₂S

CAS No.

2089148-72-9

SMILES

O=S(N1CCN(C2=CC=C([[email protected]]3CN(C4C(C(F)=CC=C5)=C5CC4)C[[email protected]@H]3N(C)C)C=C2)CC1)(C)=O

Shipping

Room temperature in continental US; may vary elsewhere

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (205.49 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.0549 mL 10.2743 mL 20.5486 mL
5 mM 0.4110 mL 2.0549 mL 4.1097 mL
10 mM 0.2055 mL 1.0274 mL 2.0549 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 1.67 mg/mL (3.43 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 1.67 mg/mL (3.43 mM); Clear solution

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 1.67 mg/mL (3.43 mM); Clear solution

*All of the co-solvents are provided by MCE.
References
Kinase Assay

The embryonic ectoderm development (EED) protein is an essential subunit of Polycomb repressive complex 2 (PRC2). A-395 antagonizes of the H3K27me3 binding functions of EED. A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2. A-395 is capable of competing for H3K27me3 peptide binding to EED, with an IC50 of 7 nM. A-395, but not the close chemical analog A-395N, modulates activity of PRC2 in cells by potently reducing the H3K27 methyl mark in a highly selective manner. A-395 treatment inhibits both H3K27me2 and H3K27me3, with IC50 values of 390 nM and 90 nM, respectively. Furthermore, A-395 treatment results in growth inhibition of human tumor cell lines sensitive to SAM-competitive EZH2 inhibitors[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

1,000 multiple myeloma cells are seeded in each well of 96-well cell culture plates and treated with A-395 (0.001-100 μM) or DMSO control for 10 d before the cell proliferation assay. Cell proliferation assays are conducted with the CellTiter-Glo Luminescent Cell Viability Assay[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Mice[1]

SCID mice are inoculated with the human Pfeiffer cell line and these xenografts are grown to size match at ∼200 mm3. Mice are subsequently treated with vehicle control, A-395 and A-395N at 300 mg/kg s.c. two times per week for 5 weeks or GSK126 at 50 mg/kg i.p. once per day for 36 d. Tumor volume is measured at different intervals and is represented by the average ± s.d. (eight mice per group)[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
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Product Name:
A-395
Cat. No.:
HY-101512
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