Entinostat (MS-275)

Catalog No.S1053 Batch:S105302

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Technical Data

Formula

C21H20N4O3
Molecular Weight 376.41 CAS No. 209783-80-2
Solubility (25°C)* In vitro DMSO 75 mg/mL (199.25 mM)
Water Insoluble
Ethanol 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 Entinostat (MS-275, SNDX-275) strongly inhibits HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM in cell-free assays, compared with HDACs 4, 6, 8, and 10. Entinostat induces autophagy and apoptosis. Phase 3.
Targets
HDAC1 [2]
(Cell-free assay)		 HDAC3 [2]
(Cell-free assay)
0.51 μM 1.7 μM
In vitro MS-275 shows inhibitory to HDACs by 2'-amino group. MS-275 induces accumulation of p21WAF1/CIP1 and gelsolin in K562 cell. MS-275 could reduce S-phase cells and induce G1-phase cells in A2780 cell. MS-275 inhibits the proliferation of human tumor cell lines including A2780, Calu-3, HL-60, K562, St-4, HT-29, KB-3-1, Capan-1, 4-1St and HCT-15 with IC50 from 41.5 nM to 4.71 μM, which due to HAD-inhibition. [1] MS-275 is not sensitive to other HDACs (4, 6, 8 and 10) with IC50 about/above 100 μM. [2] MS-275 shows great inhibition to human leukemia and lymphoma cells, including U937, HL-60, K562, and Jurkat. MS-275 also decreases expression of cyclin D1 and the antiapoptotic proteins Mcl-1 and XIAP. [3]
In vivo MS-275 exhibits great antitumor activity against human tumor xenografts except HCT-15 at 49 mg/kg. [1] MS-275 demonstrates promising therapeutic potential in both solid and hematologic malignancies, as well as regulation of physiologic and aberrant gene expression. [4] MS-275, combination with IL-2, has great antitumor activity to renal cell carcinoma xenograft model, which due to decreased T regulatory cells and increased splenocytes. [5]

Protocol (from reference)

Kinase Assay:

[6]
  • Standard HDAC Assays

    Rat liver enzyme is diluted 1:6 with HDAC buffer. Recombinant human HDACs are diluted 1:4 in HDAC buffer. For standard HDAC assays, 60 μL of HDAC buffer is mixed with 10 μL of diluted enzyme solution at 30 °C. The HDAC reaction is started by adding 30 μL substrate solution in HDAC buffer followed by 30 min of incubation at 30 °C. The reaction is stopped by adding 100 μL trypsin solutions (10 mg/ml trypsin in 50 mM Tris-HCl [pH 8.0], 100 mM NaCl, 2 μM TSA). After a 20 min incubation period at 30 °C, the release of AMC is monitored by measuring the fluorescence at 460 nm (λex = 390 nm). Fluorescence intensity is calibrated using free AMC. For standard time course experiments, 20 pmol of substrate is used in the initial 100 μL HDAC reaction. Km and Vmax values are determined by measuring the fluorescence AMC generated by enzymatic cleavage of 2–50 pmol of substrate. The experimental data are analyzed using a Hanes plot. The AMC signals are recorded against a blank with buffer and substrate but without the enzyme.
Cell Assay:

[2]
  • Cell lines

    A2780, Calu-3, HL-60, K562, St-4, HT-29, KB-3-1, Capan-1, 4-1St and HCT-15 cells

  • Concentrations

    ~ 10 μM

  • Incubation Time

    3 days

  • Method

    Cancer cells (5 × 103) are seeded into each well of 96-well plates and cultured with graded concentrations of MS-275 for 3 days. The cells are stained with 0.1 mg/mL neutral red for 1 hour in a CO2-incubator, and, after aspiration of the medium, OD540 of the neutral red solubilized with 50 μL of ethanol and 150 μL of 0.1 M Na2HPO4 is measured. The IC50 value is determined by plotting growth inhibition of the cells against the logarithm of the drug concentration.
Animal Study:

[1]
  • Animal Models

    A2780, HT-29, HTC-15, KB-3-1, 4-1St, St-4, Capan-1 and Calu-3 cells are injected subcutaneously into the flank of nude mice.

  • Dosages

    12.3, 24.5 and 49 mg/kg

  • Administration

    Administered orally once daily 5 days per week for 4 weeks

Customer Product Validation

Data from [Data independently produced by PLoS Biol, 2014, 12, e1001758]

Data from [Biochem Biophys Res Commun, 2014, 10.1016/j.bbrc.2014.01.184]

Data from [Biochem Biophys Res Commun, 2014, 10.1016/j.bbrc.2014.01.184]

Data from [Data independently produced by PLoS One, 2013, 8, e74930]

Selleck's Entinostat (MS-275) has been cited by 444 publications

A functional personalised oncology approach against metastatic colorectal cancer in matched patient derived organoids [ NPJ Precis Oncol, 2024, 8(1):52] PubMed: 38413740
Romidepsin and afatinib abrogate JAK-STAT signaling and elicit synergistic antitumor effects in cutaneous T-cell lymphoma [ J Invest Dermatol, 2024, S0022-202X(23)03210-4] PubMed: 38219917
HDAC Inhibition Induces CD26 Expression on Multiple Myeloma Cells via the c-Myc/Sp1-mediated Promoter Activation [ Cancer Res Commun, 2024, 4(2):349-364] PubMed: 38284882
Single-cell RNA sequencing identifies critical transcription factors of tumor cell invasion induced by hypoxia microenvironment in glioblastoma [ Theranostics, 2023, 13(11):3744-3760] PubMed: 37441593
Novel hydroxamic acid derivative induces apoptosis and constrains autophagy in leukemic cells [ Journal of Advanced Research, 2023, 10.1016/j.jare.2023.07.005] PubMed: None
HDAC3 Inhibition Promotes Antitumor Immunity by Enhancing CXCL10-Mediated Chemotaxis and Recruiting of Immune Cells [ Cancer Immunol Res, 2023, 11(5):657-673] PubMed: 36898011
Differential regulation of H3K9/H3K14 acetylation by small molecules drives neuron-fate-induction of glioma cell [ Cell Death Dis, 2023, 14(2):142] PubMed: 36805688
Elucidating the direct effects of the novel HDAC inhibitor bocodepsin (OKI-179) on T cells to rationally design regimens for combining with immunotherapy [ Front Immunol, 2023, 14:1260545] PubMed: 37744352
Elucidating the direct effects of the novel HDAC inhibitor bocodepsin (OKI-179) on T cells to rationally design regimens for combining with immunotherapy [ Front Immunol, 2023, 14:1260545] PubMed: 37744352
Porcine Epidemic Diarrhea Virus Antagonizes Host IFN-λ-Mediated Responses by Tilting Transcription Factor STAT1 toward Acetylation over Phosphorylation To Block Its Activation [ mBio, 2023, e0340822.] PubMed: 37052505

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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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