Antibodies
Entinostat (MS-275)
- 貨號 Cat. No.
- S1053
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Entinostat (MS-275)
Entinostat (MS-275) strongly inhibits HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM, compared with HDACs 4, 6, 8, and 10. Phase 1/2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Entinostat (MS-275) strongly inhibits HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM, compared with HDACs 4, 6, 8, and 10. Phase 1/2. | |||||
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| Targets | HDAC1 | HDAC3 | ||||
| IC50 | 0.51 μM | 1.7 μM [2] | ||||
| 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] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay:
| 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. |
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Cell Assay:
| Cell lines | A2780, Calu-3, HL-60, K562, St-4, HT-29, KB-3-1, Capan-1, 4-1St and HCT-15 cells |
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| 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:
| 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. |
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| Dosages | 12.3, 24.5 and 49 mg/kg |
| Administration | Administered orally once daily 5 days per week for 4 weeks |
| Solubility | 30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01349959 | Recruiting | Estrogen Receptor-negative Breast Cancer|Estrogen Receptor-positive Breast Cancer|HER2-negative Breast Cancer|Male Breast Cancer|Progesterone Receptor-negative Breast Cancer etc. | National Cancer Institute (NCI) | 2011-04 | Phase 2 |
| NCT01305499 | Recruiting | Acute Myeloid Leukemia | Sidney Kimmel Comprehensive Cancer Center | 2011-07 | Phase 2 |
| NCT01434303 | Recruiting | HER2-positive Breast Cancer|Inflammatory Breast Cancer|Male Breast Cancer|Recurrent Breast Cancer|Stage IV Breast Cancer | National Cancer Institute (NCI) | 2012-01 | Phase 1|Phase 2 |
| NCT01594398 | Recruiting | Lung Cancer|Non Small Cell Lung Cancer (NSCLC)|Breast Cancer|ER+ Breast Cancer | Syndax Pharmaceuticals | 2012-05 | Phase 1 |
| NCT01846897 | Recruiting | Epigenetic Therapy | Sidney Kimmel Comprehensive Cancer Center | 2013-04 | Phase 2 |
Chemical Information
Download Entinostat (MS-275) SDF
| Molecular Weight (MW) | 376.41 |
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| Formula | C21H20N4O3 |
| CAS No. | 209783-80-2 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | SNDX-275 |
| Solubility (25°C) * | In vitro | DMSO | 75 mg/mL (199 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 30% propylene glycol, 5% Tween 80, 65% D5W, | 30 mg/mL | |
| * <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. | |||
| Chemical Name | pyridin-3-ylmethyl 4-((2-aminophenyl)carbamoyl)benzylcarbamate |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.37641 | 3.7641 | 7.5282 | 11.2923 |
Customer Reviews (12)
 Click to enlarge | Rating | |
| Source | Biochemical and Biophysical Research Communications, 414 (2011) 25–30. Entinostat (MS-275) purchased from Selleck | |
| Method | qRT-PCR | |
| Cell Lines | HEK-293cells | |
| Concentrations | 0.37-10uM | |
| Incubation Time | ||
| Results | Analysis of mRNA changes following MS-275 treatment revealed a different profile than what was observed with the paninhibitors. Class I specific HDAC inhibition increased both total and exon 7 included mRNA. However, the fold increases of the total transcript exceeded that of exon 7 included. |
Product Citations (31)
Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. [Bantscheff M, et al. Nat Biotechnol 2011;29(3):255-65]
Selective class I histone deacetylase inhibition suppresses hypoxia-induced cardiopulmonary remodeling through an antiproliferative mechanism. [Cavasin MA, et al. Circ Res 2012;110(5):739-48]
Selective cancer targeting with prodrugs activated by histone deacetylases and a tumour-associated protease. [Ueki N, et al. Nat Commun 2013;4:2735]
