Entinostat (MS-275)

Katalognr.S1053 Batch:S105305

Skriv ut

Tekniska data

Formel

C21H20N4O3
Molekylvikt 376.41 CAS-nr. 209783-80-2
Löslighet (25°C)* In vitro DMSO 75 mg/mL (199.25 mM)
Water Insoluble
Ethanol Insoluble
In Vivo (Tillsätt lösningsmedel till produkten individuellt och i ordning.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.

 4.000mg/ml (10.63mM) Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml betyder svårlösligt eller olösligt.
* Vänligen notera att Selleck testar lösligheten för alla förbindelser internt, och den faktiska lösligheten kan skilja sig något från publicerade värden. Detta är normalt och beror på små variationer mellan olika partier.
* Rumstempererad frakt (Stabilitetstester visar att denna produkt kan fraktas utan några kylåtgärder.)

Beredning av stamlösningar

Biologisk aktivitet

Beskrivning Entinostat (MS-275, SNDX-275) hämmar starkt HDAC1 och HDAC3 med IC50 på 0,51 μM och 1,7 μM i cellfria analyser, jämfört med HDACs 4, 6, 8 och 10. Denna förening inducerar autophagy och apoptosis. Fas 3.
Mål
HDAC1
(Cell-free assay)		 HDAC3
(Cell-free assay)
0.51 μM 1.7 μM
In vitro Entinostat (MS-275) shows inhibitory to HDACs by 2'-amino group. It induces accumulation of p21WAF1/CIP1 and gelsolin in K562 cell, and could reduce S-phase cells and induce G1-phase cells in A2780 cell. This compound 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. It is not sensitive to other HDACs (4, 6, 8 and 10) with IC50 about/above 100 μM. It 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.
In Vivo Entinostat (MS-275) exhibits great antitumor activity against human tumor xenografts except HCT-15 at 49 mg/kg. It demonstrates promising therapeutic potential in both solid and hematologic malignancies, as well as regulation of physiologic and aberrant gene expression. When combined with IL-2, this compound has great antitumor activity in a renal cell carcinoma xenograft model, which is due to decreased T regulatory cells and increased splenocytes.

Protokoll (från referens)

Kinasanalys:

[6]
  • Standard HDAC-analyser

    Råttleverenzym späds 1:6 med HDAC-buffert. Rekombinanta humana HDACs späds 1:4 i HDAC-buffert. För standard HDAC-analyser blandas 60 μL HDAC-buffert med 10 μL utspädd enzymlösning vid 30 °C. HDAC-reaktionen startas genom att tillsätta 30 μL substratlösning i HDAC-buffert följt av 30 minuters inkubation vid 30 °C. Reaktionen stoppas genom att tillsätta 100 μL trypsinlösningar (10 mg/ml trypsin i 50 mM Tris-HCl [pH 8,0], 100 mM NaCl, 2 μM TSA). Efter en 20 minuters inkubationsperiod vid 30 °C övervakas frisättningen av AMC genom att mäta fluorescensen vid 460 nm (λex = 390 nm). Fluorescensintensiteten kalibreras med fritt AMC. För standardtidskursförsök används 20 pmol substrat i den initiala 100 μL HDAC-reaktionen. Km- och Vmax-värden bestäms genom att mäta fluorescensen AMC som genereras av enzymatisk klyvning av 2–50 pmol substrat. Experimentella data analyseras med en Hanes-plot. AMC-signalerna registreras mot en blank med buffert och substrat men utan enzymet.
Cellanalys:

[2]
  • Cellinjer

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

  • Koncentrationer

    ~ 10 μM

  • Inkubationstid

    3 days

  • Metod

    Cancer cells (5 × 103) are seeded into each well of 96-well plates and cultured with graded concentrations of Entinostat (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.
Djurstudie:

[1]
  • Djurmodeller

    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.

  • Doseringar

    12.3, 24.5 and 49 mg/kg

  • Administrering

    Administered orally once daily 5 days per week for 4 weeks

Referenser

  • https://pubmed.ncbi.nlm.nih.gov/10200307/
  • http://cancerres.aacrjournals.org/content/64/7_Supplement/567.2.abstract?sid=570927c9-edf5-40d3-a10d-e404e8be205b
  • https://pubmed.ncbi.nlm.nih.gov/12839953/
  • https://pubmed.ncbi.nlm.nih.gov/20451583/
  • https://pubmed.ncbi.nlm.nih.gov/17671140/
  • https://pubmed.ncbi.nlm.nih.gov/12573699/

Kundvalidering av produkt

(A) U87 cells were cultured in the presence of DMSO, 1 uM MS-275 alone, 100 ng/ml IFN-λ1 alone, or both for the course of 4 d. Cell numbers were manually determined by hemacytometer counting at the indicated time points. (B, F) Cell proliferation of U87 cells or U87 spheroids in 3D culture with indicated treatment were performed using the WST-1 assay, which measures active cellular metabolism. (C) U87 spheroid formation in 3D culture was photographed at day 14 in culture (representative images are shown; 200x magnification). (D-E) Quantification of the relative sizes and numbers of U87 spheroids in (C). (G) Cell cycle analysis was performed in U87 cells with indicated treatment using propidium iodide staining. Numbers in the histogram show fractions (percent) of sub-G1, N, 2N, and polyploidy from left to right. (H) U87 cells with indicated treatment were stained with Annexin V-FITC and 7-AAD. Numbers indicate the percentage of FITC-positive cells (upper left quadrant). FITC, fluorescein isothiocyanate; 7-AAD, 7-Aminoactinomycin. In all panels, data represent the mean and SEM of at least three experiments.

Data från [ PLoS Biol , 2014 , 12, e1001758 ]

<p>HCT116 p53 null cells were treated with different HDACIs (1 μM TSA, 5 μM M344, 1 μM MS-275, 5 mM But, 10 mM VPA) for 24 h, and their expression of GRP78, PERK-eIF2α axis and ATF4, ATF3, CHOP and DR5 proteins.</p>

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

<p>HCT116 p53 null cells were treated with different HDACIs (1 μM TSA, 5 μM M344, 1 μM MS-275, 5 mM But, 10 mM VPA) for 24 h. ATF4, ATF3, CHOP and DR5 proteins were measured by Western blot.</p>

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

B. Confluent quiescent foreskin fibroblasts were treated with HDAC1 inhibitor or vehicle for 24 hours. Type I procollagen protein levels in whole cell lysates were determined by immunoblotting. A representative result of three independent experiments is shown. The band density wasevaluated by densitometry. C. Under the same conditions, mRNA levels of the α1(I) collagen (COL1A1) gene were determined using reversetranscription quantitative real-time PCR. The graph represents -fold change in COL1A1 mRNA levels in comparison to unstimulated controls, whichwere arbitrarily set at 100. The mean and SD from three separate experiments are shown. * p<0.05 versus control cells treated with vehicle.

Data från [ PLoS One , 2013 , 8, e74930 ]

Sellecks Entinostat (MS-275) Har citerats av 442 Publikationer

Epigenetic remodeling in sarcoma promotes T-cell infiltration via modulation of the Hippo pathway [ J Immunother Cancer, 2026, 14(4)e014601] PubMed: 41922083
Altered fibroblast-like synoviocyte epigenetics is responsible for deficient NUB1 expression in rheumatoid arthritis [ Sci Rep, 2026, 16(1)8128] PubMed: 41667591
Mechanisms of HIV Latency in Hematopoietic Progenitors: GFI1 as a Key Regulator [ bioRxiv, 2026, 2026.02.19.706859] PubMed: 41756862
Reprogramming aerobic metabolism mitigates Streptococcus pyogenes tissue damage in a mouse necrotizing skin infection model [ Nat Commun, 2025, 16(1):2559] PubMed: 40089471
PROX1 is an early driver of lineage plasticity in prostate cancer [ J Clin Invest, 2025, 135(11)e187490] PubMed: 40454483
Early growth response 1 as a key regulator of PD-L1 expression and immune evasion in extranodal NK/T-cell lymphoma [ Blood Cancer J, 2025, 15(1):108] PubMed: 40514360
HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy [ Leukemia, 2025, 10.1038/s41375-025-02584-9] PubMed: 40175628
Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition [ J Exp Clin Cancer Res, 2025, 44(1):21] PubMed: 39844304
Dual targeting of CDK6 and LSD1 is synergistic and overcomes differentiation blockade in AML [ EMBO Mol Med, 2025, 10.1038/s44321-025-00296-2] PubMed: 40883610
Engineering a multilayered 3D stromal barrier model for quantitative analysis of T cell infiltration and cytotoxicity [ Acta Biomater, 2025, S1742-7061(25)00677-4] PubMed: 40939760

RETURPOLICY
Selleck Chemicals villkorslösa returpolicy säkerställer en smidig online-shoppingupplevelse för våra kunder. Om du på något sätt är missnöjd med ditt köp kan du returnera artikeln/artiklarna inom 7 dagar efter mottagandet. I händelse av produktkvalitetsproblem, antingen protokollrelaterade eller produktrelaterade problem, kan du returnera artikeln/artiklarna inom 365 dagar från det ursprungliga köpdatumet. Vänligen följ instruktionerna nedan vid retur av produkter.

FRAKT OCH FÖRVARING
Sellecks produkter transporteras i rumstemperatur. Om du tar emot produkten i rumstemperatur kan du vara trygg; Sellecks kvalitetskontrollavdelning har utfört experiment för att verifiera att placering i normal temperatur under en månad inte påverkar den biologiska aktiviteten hos pulverprodukter. Efter insamling ska produkten förvaras i enlighet med de krav som beskrivs i databladet. De flesta av Sellecks produkter är stabila under de rekommenderade förhållandena.

EJ AVSEDD FÖR ANVÄNDNING PÅ MÄNNISKOR, INOM VETERINÄRDIAGNOSTIK ELLER FÖR TERAPEUTISKT BRUK.