2. Epigenetics
  3. Histone Methyltransferase
  4. A-395

A-395 est un antagoniste des interactions protéine-protéine complexe répressif polycombique 2 (PRC2) qui inhibe puissamment le complexe trimérique PRC2 (EZH2-EED-SUZ12) avec un IC50 de 18 nM.

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

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Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 118 In-stock
Solution
10 mM * 1 mL in DMSO USD 118 In-stock
Solid
1 mg USD 52 In-stock
5 mg USD 110 In-stock
10 mg USD 190 In-stock
25 mg USD 450 In-stock
50 mg USD 720 In-stock
100 mg USD 1150 In-stock
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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[1].

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].

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

A-395 Related Antibodies
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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Molecular Weight

486.65

Formula

C26H35FN4O2S
CAS No.
Appearance

Solid

Color

White to yellow

SMILES

O=S(N1CCN(C2=CC=C([C@H]3CN(C4C(C(F)=CC=C5)=C5CC4)C[C@@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 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (205.49 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

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

    Solubility: ≥ 0.83 mg/mL (1.71 mM); Clear solution

    This protocol yields a clear solution of ≥ 0.83 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (8.3 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

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

    Solubility: ≥ 0.83 mg/mL (1.71 mM); Clear solution

    This protocol yields a clear solution of ≥ 0.83 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (8.3 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.34%

COA (252 KB) LCMS (266 KB)

Handling Instructions (2659 KB)
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

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.0549 mL 10.2743 mL 20.5486 mL 51.3716 mL
5 mM 0.4110 mL 2.0549 mL 4.1097 mL 10.2743 mL
10 mM 0.2055 mL 1.0274 mL 2.0549 mL 5.1372 mL
15 mM 0.1370 mL 0.6850 mL 1.3699 mL 3.4248 mL
20 mM 0.1027 mL 0.5137 mL 1.0274 mL 2.5686 mL
25 mM 0.0822 mL 0.4110 mL 0.8219 mL 2.0549 mL
30 mM 0.0685 mL 0.3425 mL 0.6850 mL 1.7124 mL
40 mM 0.0514 mL 0.2569 mL 0.5137 mL 1.2843 mL
50 mM 0.0411 mL 0.2055 mL 0.4110 mL 1.0274 mL
60 mM 0.0342 mL 0.1712 mL 0.3425 mL 0.8562 mL
80 mM 0.0257 mL 0.1284 mL 0.2569 mL 0.6421 mL
100 mM 0.0205 mL 0.1027 mL 0.2055 mL 0.5137 mL
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A-395 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

A-3952089148-72-9A395A 395Histone MethyltransferaseInhibitorinhibitorinhibit

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