现货，Entinostat (MS-275, SNDX-275) ，目录号 S1053，CAS号:209783-80-2， HDAC YZ剂，美国Selleck_详细资料

产品信息

英文名： Entinostat (MS-275, SNDX-275) CAS号： 209783-80-2 供应商：美国Selleck南京办事处保质期：两年数量：大量保存条件：零下二十摄氏度低温保存规格： 10mg

信号转导通路:  HDAC-HSP-Aurora >> HDAC >> HDAC YZ剂 >> Entinostat (MS-275, SNDX-275)
http://selleck.cn/ms-275-S1053.html
技术数据:

分子量(MW): 376.41

化学式:
C₂₁H₂₀N₄O₃

溶解度: DMSO ≥75mg/mL   Water <1mg/mL   Ethanol <1mg/mL

纯度: >99%

稳定性: at -20℃ 2 years

CAS号: 209783-80-2

生物活性

Entinostat (MS-275, SNDX-275) is a potent HDAC inhibitor with IC50 of 0.3 and 8µM for HDAC1 and HDAC3, respectively. Entinostat (MS-275, SNDX-275) is synthetic benzamide derivative with potential antineoplastic activity. Entinostat (MS-275, SNDX-275) has no inhibitory activity towards HDAC8 (IC50>100 µM). Entinostat (MS-275, SNDX-275) appears to exert dose-dependent effects in human leukemia cells at low concentrations in human prostate cancer cell lines. Entinostat (MS-275, SNDX-275) exerted growth arrest in PC-3 and LNCaP cells, and induced cell death in DU-145 cells. ^[1][2][3]

参考文献

MS-275, a novel histone deacetylase inhibitor with selectivity against HDAC1, induces degradation of FLT3 via inhibition of chaperone function of heat shock protein 90 in AML cells Chie Nishioka ,Takayuki Ikezoe,et al Leukemia Research 2008;32：1382–1392

AntitumorActivityof theHistoneDeacetylase Inhibitor MS-275 in Prostate Cancer Models David Z. Qian, Yong-Feng Wei,et al. TheProstate 2007;67:1182^1193

Experimental therapy of malignant gliomas using the inhibitor of histone deacetylase MS-275 Eric Hahnen, Christian Tränkle, et al. Mol Cancer Ther 2006;5:1248-1255

客户反馈数据

Western blot analysis of Acetyl-H3 and H3. 0-20μM MS-275 was added.

Inhibition of LSD1 activity by HDAC inhibitors. a MDA-MB-231 and MDA-MB-468 cells were exposed to indicated HDAC inhibitors for 24 h.

LSD1 and HDAC inhibitors exhibit synergistic growth inhibition. Cells were simultaneously treated with pargyline or HDAC inhibitors for 48 h.

Inhibition of HDAC1-mediated DNMT1 deacetylation promotes DNMT1 proteasomal degradation. (A) Knockout of HAUSP potentiates HDAC inhibitor (HDACi)–induced DNMT1 degradation. Parental or HAUSP KO DLD1 cells were treated or not with 5 mM HDACi MS-275 for 72 hours and cell lysates were blotted with the indicated antibodies. (B) HDAC inhibition induces DNMT1 ubiquitination. HAUSP WT or KO cells were treated with or without HDACi for 24 hours and MG132 for 12 hours before being harvested to make cell lysates. DNMT1 immunoprecipitates were blotted with an antibody against ubiquitin. Because the abundance of DNMT1 in the HAUSP KO cells is lower than in WT cells, more KO cells were used than WT cells to obtain equal amounts of precipitated DNMT1 proteins. (C) DNMT1 is acetylated after HDACi treatment. DNMT1 immunoprecipitates from cells treated with HDACi were blotted with an antibody against acetylated lysine (Ac-K). (D) A DNMT1 acetylation site mutant is resistant to HDACi-induced degradation. HEK 293 cells were transfected with WT DNMT1 or a DNMT1 mutant lacking four known acetylation sites (K173R, K1113R, K115R, and K117R) and treated with MS-275 for 48 hours and with CHX for 24 hours. Cell lysates were blotted with the indicated antibodies. (E) Knockdown of HDAC1 decreases the abundance of DNMT1. RKO cells were treated with the indicated concentration of doxycycline (Dox) for 48 hours to induce expression of an shRNA directed against HDAC1. Western blots were performed with the indicated antibodies. (F) Knockdown of HDAC1 leads to increased acetylation of DNMT1. RKO cells expressing an inducible HDAC1 shRNA were treated with or without Dox (4 mg/ml) for 36 hours and then with MG132 for 12 hours. DNMT1 immunoprecipitates were blotted with an antibody against Ac-K. Cell lysates were also blotted with antibodies against HDAC1 and b-actin.

The E3 ligase UHRF1 ubiquitinates DNMT1. (A) HDAC inhibition enhances DNMT1 interaction with UHRF1. HEK 293 cells were transfected with plasmids expressing Myc-DNMT1 and Flag-UHRF1 and treated with or without MS-275 for 24 hours. Myc-DNMT1 immunoprecipitates were blotted with the indicated antibodies. (B and C) HDAC inhibition enhances the interaction of endogenous DNMT1 and UHRF1. Cells were treated with or without MS-275 and UHRF1 (B) or DNMT1 (C) immunoprecipitates were blotted with the indicated antibodies. (D) UHRF1 ubiquitinates DNMT1. HEK 293 cells were transfected with the indicated plasmids. Antibodies against Myc immunoprecipitates were blotted with antibody against HA to detect ubiquitinated DNMT1. Myc-DNMT1D, DNMT1 mutant lacking the HAUSP-interacting domain. UHRF1DRING, UHRF1 with a RING domain deletion. (E) Knockdown of UHRF1 blocks HDACi-induced DNMT1 degradation. HEK 293 cells were transfected with control siRNA or siRNAs against UHRF1 and treated with or without MS-275. Western blotting was performed with the indicated antibodies. (F) Overexpression of UHRF1 leads to degradation of a DNMT1 mutant lacking the HAUSP-interacting domain (DNMT1D). Full-length DNMT1 or DNMT1D was cotransfected into HEK 293 cells with the indicated expression vectors. Cell lysates were blotted with the indicated antibodies. (G) DNMT1, HAUSP, UHRF1, HDAC1, and PCNA associate with Tip60. Flag-tagged Tip60 immunoprecipitates were blotted with the indicated antibodies.

HAUSP KO cells are more sensitive to HDACi-induced apoptosis.(A) HDAC inhibition induces apoptosis inHAUSPKOcells.HAUSP WT or KO cells were treated with or without MS-275 at the indicatedconcentration for 72 hours, then fixed and stained with propidium iodide. Flowcytometric analyseswere used to profile sub-G1, G1, and G2-M cell populations. Apoptotic cells were quantified after the indicated clones were treated with either 5 or 10 mM MS-275. The means and SDs of three independent experimentswereplotted (*P<0.001, t test). (B) HDAC inhibition induces apoptosis inHAUSPKOcells but leads to G2-M arrest in WT cells.Cell cycle profiles of HAUSP WT or KOcells thatwere treated or notwith 5 mMMS-275. (C)HDACinhibition increases the abundance of apoptotic cell markers. The indicated cells were treated with or without MS-275 for 72 hours.Cell lysates were blotted with antibodies against cleaved caspase 3 and b-actin. (D) Ectopic overexpression of DNMT1 in HAUSP KO cells suppresses apoptosis. HAUSP KO clones or HAUSP KO cells inducibly

overexpressingDNMT1 were treatedwith 10 mMMS-275. Apoptotic cell populations were quantified by fluorescence-activated cell sorting (FACS) analyses (*P < 0.001, t test). Cell lysates from these cells were blotted with the indicated antibodies. (E) HDAC inhibition arrests the growth of HAUSP KO cells. DLD1, HAUSP KO, and KO cells ectopically expressing HAUSP were treated with the indicated concentration of MS-275 for 4 days. Cell numbers were determined and data from eight replicates were plotted (**P <0.001, t test). (FandG) HDACi inhibits tumor xenograft formation ofHAUSP KOcells.Athymic nudemice (five in each group)were injectedsubcutaneously and bilaterallywith cells of the indicated genotypes. Mice were treatedwith orwithout MS-275 at 15mg/kg for 4 weeks. Tumors were harvested and photographed (F). Tumor sizes of the indicated groupsweremeasuredweekly and theaveragevolumes at each timepoint were plotted (G).MANOVA analyses were performed to determine whether there was an overall difference of the tumor sizes, as well as whether there was a difference in development over time of tumor sizes between the two groups (P < 0.0001).

Histone acetylation in the spinal cord after HDACI treatment. Histone acetylation in the lumbar spinal cord of mice receiving i.t. SAHA (25 μg) or MS-275 (0.5 μg) for 30 min was analyzed by immunoblot (A, B) and immunofluorescent histochemistry (C) for antigens indicated. Animals receiving i.t. saline were used as control. Images of the H3K9/18ac signals in the left half of the lumbar spinal cord are shown in the first row in C. Immunosignals of indicated antigens in the superficial dorsal horn are presented in the rest rows in C.

如果需要长期保存，请于零下二十度低温保存。

禁止用于人体及ZL！

特定的存储和包装每个产品的信息在产品说明书上都有注明。大多数Selleck产品，在推荐的条件下存储可稳定保存两年。产品有时建议的储存温度不同，大多数建议储存在-20 ° C ，抗体及蛋白等产品建议-60℃。YZ剂属于化学试剂，可在常温下运输储存两周左右。即使如此，我们保证产品的出货量将保持产品质量的条件下，一般都会放入冰袋。望阁下收到产品后，请按照产品数据表建议适当存储。

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温馨提示：不可用于临床ZL。

分子量(MW):	376.41
化学式:	C₂₁H₂₀N₄O₃
溶解度:	DMSO ≥75mg/mL Water <1mg/mL Ethanol <1mg/mL
纯度:	>99%
稳定性:	at -20℃ 2 years
CAS号:	209783-80-2

	Western blot analysis of Acetyl-H3 and H3. 0-20μM MS-275 was added.
	Inhibition of LSD1 activity by HDAC inhibitors. a MDA-MB-231 and MDA-MB-468 cells were exposed to indicated HDAC inhibitors for 24 h.
	LSD1 and HDAC inhibitors exhibit synergistic growth inhibition. Cells were simultaneously treated with pargyline or HDAC inhibitors for 48 h.
	Inhibition of HDAC1-mediated DNMT1 deacetylation promotes DNMT1 proteasomal degradation. (A) Knockout of HAUSP potentiates HDAC inhibitor (HDACi)–induced DNMT1 degradation. Parental or HAUSP KO DLD1 cells were treated or not with 5 mM HDACi MS-275 for 72 hours and cell lysates were blotted with the indicated antibodies. (B) HDAC inhibition induces DNMT1 ubiquitination. HAUSP WT or KO cells were treated with or without HDACi for 24 hours and MG132 for 12 hours before being harvested to make cell lysates. DNMT1 immunoprecipitates were blotted with an antibody against ubiquitin. Because the abundance of DNMT1 in the HAUSP KO cells is lower than in WT cells, more KO cells were used than WT cells to obtain equal amounts of precipitated DNMT1 proteins. (C) DNMT1 is acetylated after HDACi treatment. DNMT1 immunoprecipitates from cells treated with HDACi were blotted with an antibody against acetylated lysine (Ac-K). (D) A DNMT1 acetylation site mutant is resistant to HDACi-induced degradation. HEK 293 cells were transfected with WT DNMT1 or a DNMT1 mutant lacking four known acetylation sites (K173R, K1113R, K115R, and K117R) and treated with MS-275 for 48 hours and with CHX for 24 hours. Cell lysates were blotted with the indicated antibodies. (E) Knockdown of HDAC1 decreases the abundance of DNMT1. RKO cells were treated with the indicated concentration of doxycycline (Dox) for 48 hours to induce expression of an shRNA directed against HDAC1. Western blots were performed with the indicated antibodies. (F) Knockdown of HDAC1 leads to increased acetylation of DNMT1. RKO cells expressing an inducible HDAC1 shRNA were treated with or without Dox (4 mg/ml) for 36 hours and then with MG132 for 12 hours. DNMT1 immunoprecipitates were blotted with an antibody against Ac-K. Cell lysates were also blotted with antibodies against HDAC1 and b-actin.
	The E3 ligase UHRF1 ubiquitinates DNMT1. (A) HDAC inhibition enhances DNMT1 interaction with UHRF1. HEK 293 cells were transfected with plasmids expressing Myc-DNMT1 and Flag-UHRF1 and treated with or without MS-275 for 24 hours. Myc-DNMT1 immunoprecipitates were blotted with the indicated antibodies. (B and C) HDAC inhibition enhances the interaction of endogenous DNMT1 and UHRF1. Cells were treated with or without MS-275 and UHRF1 (B) or DNMT1 (C) immunoprecipitates were blotted with the indicated antibodies. (D) UHRF1 ubiquitinates DNMT1. HEK 293 cells were transfected with the indicated plasmids. Antibodies against Myc immunoprecipitates were blotted with antibody against HA to detect ubiquitinated DNMT1. Myc-DNMT1D, DNMT1 mutant lacking the HAUSP-interacting domain. UHRF1DRING, UHRF1 with a RING domain deletion. (E) Knockdown of UHRF1 blocks HDACi-induced DNMT1 degradation. HEK 293 cells were transfected with control siRNA or siRNAs against UHRF1 and treated with or without MS-275. Western blotting was performed with the indicated antibodies. (F) Overexpression of UHRF1 leads to degradation of a DNMT1 mutant lacking the HAUSP-interacting domain (DNMT1D). Full-length DNMT1 or DNMT1D was cotransfected into HEK 293 cells with the indicated expression vectors. Cell lysates were blotted with the indicated antibodies. (G) DNMT1, HAUSP, UHRF1, HDAC1, and PCNA associate with Tip60. Flag-tagged Tip60 immunoprecipitates were blotted with the indicated antibodies.
	HAUSP KO cells are more sensitive to HDACi-induced apoptosis.(A) HDAC inhibition induces apoptosis inHAUSPKOcells.HAUSP WT or KO cells were treated with or without MS-275 at the indicatedconcentration for 72 hours, then fixed and stained with propidium iodide. Flowcytometric analyseswere used to profile sub-G1, G1, and G2-M cell populations. Apoptotic cells were quantified after the indicated clones were treated with either 5 or 10 mM MS-275. The means and SDs of three independent experimentswereplotted (P<0.001, t test). (B) HDAC inhibition induces apoptosis inHAUSPKOcells but leads to G2-M arrest in WT cells.Cell cycle profiles of HAUSP WT or KOcells thatwere treated or notwith 5 mMMS-275. (C)HDACinhibition increases the abundance of apoptotic cell markers. The indicated cells were treated with or without MS-275 for 72 hours.Cell lysates were blotted with antibodies against cleaved caspase 3 and b-actin. (D) Ectopic overexpression of DNMT1 in HAUSP KO cells suppresses apoptosis. HAUSP KO clones or HAUSP KO cells inducibly overexpressingDNMT1 were treatedwith 10 mMMS-275. Apoptotic cell populations were quantified by fluorescence-activated cell sorting (FACS) analyses (P < 0.001, t test). Cell lysates from these cells were blotted with the indicated antibodies. (E) HDAC inhibition arrests the growth of HAUSP KO cells. DLD1, HAUSP KO, and KO cells ectopically expressing HAUSP were treated with the indicated concentration of MS-275 for 4 days. Cell numbers were determined and data from eight replicates were plotted (**P <0.001, t test). (FandG) HDACi inhibits tumor xenograft formation ofHAUSP KOcells.Athymic nudemice (five in each group)were injectedsubcutaneously and bilaterallywith cells of the indicated genotypes. Mice were treatedwith orwithout MS-275 at 15mg/kg for 4 weeks. Tumors were harvested and photographed (F). Tumor sizes of the indicated groupsweremeasuredweekly and theaveragevolumes at each timepoint were plotted (G).MANOVA analyses were performed to determine whether there was an overall difference of the tumor sizes, as well as whether there was a difference in development over time of tumor sizes between the two groups (P < 0.0001).
	Histone acetylation in the spinal cord after HDACI treatment. Histone acetylation in the lumbar spinal cord of mice receiving i.t. SAHA (25 μg) or MS-275 (0.5 μg) for 30 min was analyzed by immunoblot (A, B) and immunofluorescent histochemistry (C) for antigens indicated. Animals receiving i.t. saline were used as control. Images of the H3K9/18ac signals in the left half of the lumbar spinal cord are shown in the first row in C. Immunosignals of indicated antigens in the superficial dorsal horn are presented in the rest rows in C.

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