A-395 (A395) |
| Catalog No.GC33187 |
A-395(A395)는 18 nM의 IC50으로 삼량체 PRC2 복합체(EZH2-EED-SUZ12)를 강력하게 억제하는 폴리콤 억제 복합체 2(PRC2) 단백질-단백질 상호작용의 길항제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2089148-72-9
Sample solution is provided at 25 µL, 10mM.
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A-395 is a novel 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.
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].
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].
[1]. He Y, et al. The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat Chem Biol. 2017 Apr;13(4):389-395.
Kinase experiment: | 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]. |
Cell experiment: | 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]. |
Animal experiment: | 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]. |
References: [1]. He Y, et al. The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat Chem Biol. 2017 Apr;13(4):389-395. | |
| Cas No. | 2089148-72-9 | SDF | |
| Canonical 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 | ||
| Formula | C26H35FN4O2S | M.Wt | 486.65 |
| Solubility | DMSO : 100 mg/mL (205.49 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0549 mL | 10.2743 mL | 20.5486 mL |
| 5 mM | 0.411 mL | 2.0549 mL | 4.1097 mL |
| 10 mM | 0.2055 mL | 1.0274 mL | 2.0549 mL |
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