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Sepantronium Bromide (YM155)

Sepantronium Bromide(YM155)是一種有效的survivin抑制藥，通過(guò)抑制Survivin啟動(dòng)子活性而發(fā)揮作用，在HeLa-SURP-luc 和 CHO-SV40-luc細(xì)胞中IC50為0.54 nM；對(duì)SV40啟動(dòng)子活性抑制作用不顯著，能夠輕微抑制Survivin與XIAP相互作用。YM155 在乳腺癌細(xì)胞中可下調(diào) survivin 和 XIAP、調(diào)節(jié)自噬并誘導(dǎo)自噬依賴(lài)的DNA損傷。Phase 2。

Sepantronium Bromide (YM155) Chemical Structure

Sepantronium Bromide (YM155) Chemical Structure

CAS: 781661-94-7

規(guī)格 價(jià)格 庫(kù)存 購(gòu)買(mǎi)數(shù)量
10mM (1mL in DMSO) 918.45 現(xiàn)貨
5mg 568.29 現(xiàn)貨
25mg 2214.29 現(xiàn)貨
100mg 6310.26 現(xiàn)貨
1g 22850.1 現(xiàn)貨
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Sepantronium Bromide (YM155)相關(guān)產(chǎn)品

相關(guān)信號(hào)通路圖

Survivin Signaling Pathways

Survivin信號(hào)通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系 實(shí)驗(yàn)類(lèi)型 給藥濃度 孵育時(shí)間 活性描述 文獻(xiàn)信息
WSU-DLCL2 Growth Inhibition Assay 10 nM 24 h inhibits cell proliferation 24486595
SU-DHL-8 Growth Inhibition Assay 10 nM 24 h inhibits cell proliferation 24486595
DB Growth Inhibition Assay 10 nM 24 h inhibits cell proliferation 24486595
TE13 Growth Inhibition Assay 0-100 nM 24/48 h decreases cell viability in a dose-dependent manner 25139395
Eca109 Growth Inhibition Assay 0-100 nM 24/48 h decreases cell viability in a dose-dependent manner 25139395
TE13 Function Assay 1-50 nM 48 h suppresses survivin expression in a dose dependent manner 25139395
Eca109 Function Assay 1-50 nM 48 h suppresses survivin expression in a dose dependent manner 25139395
INA-6? Apoptosis Assay 0-50 nM 24 h induces apoptosis 25296978
U-266 Apoptosis Assay 0-50 nM 24 h induces apoptosis 25296978
SK-MM-2 Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
KMS-12-BM Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
MOLP-2 Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
L-363 Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
OPM-2 Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
NCI-H929 Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
HG-1 Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
MOLP-8 Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
U-266 Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
INA-6 Growth Inhibition Assay 0-500 nM 48 h inhibits cell growth in a dose-dependent manner 25296978
SACC-83 Function Assay 5 nM 48 h decreases nuclear expression of HIF-1α 25485635
AGS? Growth Inhibition Assay 10/20 nM 48 h inhibits cell growth in a dose-dependent manner 25635055
KATOIII Growth Inhibition Assay 10/20 nM 48 h inhibits cell growth in a dose-dependent manner 25635055
U-CH1? Growth Inhibition Assay 0-5 μM 24/48 h IC50=9.03?nM for 48h 25640185
MUG-Chor? Growth Inhibition Assay 0-5 μM 24/48 h IC50=7.05?nM for 48h 25640185
MV4-11 Function Assay 0–1?μM 72 h induces downregulation of Survivin 25659731
Kasumi-1 Function Assay 0–1?μM 72 h induces downregulation of Survivin 25659731
AML-193 Function Assay 0–1?μM 72 h induces downregulation of Survivin 25659731
CMK Function Assay 0–1?μM 72 h induces downregulation of Survivin 25659731
THP-1 Function Assay 0–1?μM 72 h induces downregulation of Survivin 25659731
M-07e Function Assay 0–1?μM 72 h induces downregulation of Survivin 25659731
THP-1 Apoptosis Assay 1?μM 72 h induces apoptosis 25659731
ACC-2 Growth Inhibition Assay 0-100 nM 24 h inhibits cell growth in a dose-dependent manner 24370995
ACC-2 Apoptosis Assay 0-20 nM 24 h induces apoptosis in a dose-dependent manner 24370995
ACC-2 Function Assay 0-20 nM 24 h increases the conversion of LC3I to LC3II 24370995
BFTC905 Growth Inhibition Assay 0-1000 nM 48 h? IC50=20 nM, inhibits cell growth in a dose-dependent manner 24297644
T24 Growth Inhibition Assay 0-1000 nM 48 h? IC50=20 nM, inhibits cell growth in a dose-dependent manner 24297644
TSGH8301? Growth Inhibition Assay 0-1000 nM 48 h? IC50=20 nM, inhibits cell growth in a dose-dependent manner 24297644
BFTC909 Growth Inhibition Assay 0-1000 nM 48 h? IC50=20 nM, inhibits cell growth in a dose-dependent manner 24297644
BFTC905 Apoptosis Assay 20 nM 48 h induces apoptosis 24297644
BFTC905 Function Assay 20 nM 48 h decreases the expression of LC3B-II 24297644
A2780p Function Assay 0-100 nM 24 h induces Survivin downregulation? 24262875
A2780cis Function Assay 0-100 nM 24 h induces Survivin downregulation? 24262875
A2780p Apoptosis Assay 5-100 nM 24/48 h increases apoptosis in a concentration-dependent manner 24262875
A2780cis Apoptosis Assay 5-100 nM 24/48 h increases apoptosis in a concentration-dependent manner 24262875
SH-SY5Y Apoptosis Assay 1/10/100 μM 72 h induces apoptosis in a dose-dependent manner 24254560
HL-60? Function Assay 1?μM 6/12/24 h inhibits the expression of survivin 23618862
U937? Function Assay 1?μM 6/12/24 h inhibits the expression of survivin 23618862
HL-60 Apoptosis Assay 0.1/1 μM 8 h induces apoptosis 23618862
Sk-NEP-1? Growth Inhibition Assay 1-10000 nM 24 h IC50=100 nM 23267699
SK-NEP-1? Apoptosis Assay 50/100 nM 12/24 h induces apoptosis 23267699
M059J Growth Inhibition Assay 0-50 nM 48 h inhibits cell growth in a dose-dependent manner 22770110
M059K Growth Inhibition Assay 0-50 nM 48 h inhibits cell growth in a dose-dependent manner 22770110
M059J Apoptosis Assay 30 nM 24 h induces apoptosis 22770110
M059K Apoptosis Assay 30 nM 24 h induces apoptosis 22770110
PANC-1 Growth Inhibition Assay 0.01-1000 nM 48 h IC50=3.69 nM 22723871
MIAPaCa-2 Growth Inhibition Assay 0.01-1000 nM 48 h IC50=29.36 nM 22723871
BxPC-3 Growth Inhibition Assay 0.01-1000 nM 48 h IC50=30.26 nM 22723871
PANC-1 Function Assay 0-1000 nM 24 h induces downregulation of XIAP and survivin expression 22723871
MIAPaCa-2 Function Assay 0-1000 nM 24 h induces downregulation of XIAP and survivin expression 22723871
BxPC-3 Function Assay 0-1000 nM 24 h induces downregulation of XIAP and survivin expression 22723871
TC-32 Growth Inhibition Assay 0.1-1000 nM EC50=3.0 nM, inhibits cell growth in a dose-dependent manner 22961763
TC-71 Growth Inhibition Assay 0.1-1000 nM EC50=5.7 nM, inhibits cell growth in a dose-dependent manner 22961763
SK-ES-1 Growth Inhibition Assay 0.1-1000 nM EC50=2.8 nM, inhibits cell growth in a dose-dependent manner 22961763
RD-ES Growth Inhibition Assay 0.1-1000 nM EC50=6.2 nM, inhibits cell growth in a dose-dependent manner 22961763
HEK293 Growth Inhibition Assay 0.1-1000 nM EC50=23.0 nM, inhibits cell growth in a dose-dependent manner 22961763
MT-3?+?SB203580 Kinase Assay 72 h IC50=38.41 ± 5.02 nM for DR5 expression 24866585
MT-3?+?NAC Kinase Assay 72 h IC50=56.2 ± 2.07 nM for DR5 expression 24866585
SUM-159 Kinase Assay 72 h IC50=69.4 ± 4.23 nM for DR5 expression 24866585
MDA-MB-468 Kinase Assay 72 h IC50=0.07 ± 0.02 nM for DR5 expression 24866585
MT-3 Kinase Assay 72 h IC50=54.11 ± 4.32 nM for DR5 expression 24866585
SUM-159 Kinase Assay 72 h IC50=1.72 ± 0.33 nM for DR4 expression 24866585
MDA-MB-468 Kinase Assay 72 h IC50=0.11 ± 0.01 nM for DR4 expression 24866585
MT-3 Kinase Assay 72 h IC50=2.86 ± 0.54 nM for DR4 expression 24866585
SK-BR-3 Growth Inhibition Assay 72 h IC50=7 ± 0.3 nM 25220225
MDA-MB-231 Growth Inhibition Assay 72 h IC50=5 ± 1 nM 25220225
MCF7-TamC6 Growth Inhibition Assay 72 h IC50=6 ± 0.1 nM 25220225
MCF7-TamC3 Growth Inhibition Assay 72 h IC50=6 ± 3 nM 25220225
MCF7-TamR8 Growth Inhibition Assay 72 h IC50=15 ± 6 nM 25220225
MCF7-TamR7 Growth Inhibition Assay 72 h IC50=8 ± 3 nM 25220225
MCF7-TamR6 Growth Inhibition Assay 72 h IC50=8 ± 6 nM 25220225
MCF7 Growth Inhibition Assay 72 h IC50=13 ± 6 nM 25220225
ME-1 Growth Inhibition Assay 72 h IC50=0.684 ± 0.179 μM 25659731
HEL Growth Inhibition Assay 72 h IC50=0.559 ± 0.038 μM 25659731
OCI/AML3 Growth Inhibition Assay 72 h IC50=0.011 ± 0.002 μM 25659731
ML-2 Growth Inhibition Assay 72 h IC50=0.009 ± 0.002 μM 25659731
HL-60 Growth Inhibition Assay 72 h IC50=0.001 ± 0.0002 μM 25659731
AML-193 Growth Inhibition Assay 72 h IC50=0.462 ± 0.060 μM 25659731
MV4-11 Growth Inhibition Assay 72 h IC50=0.055 ± 0.028 μM 25659731
CMK Growth Inhibition Assay 72 h IC50=0.053 ± 0.009 μM 25659731
THP-1 Growth Inhibition Assay 72 h IC50=0.051 ± 0.013 μM 25659731
M-07e Growth Inhibition Assay 72 h IC50=0.040 ± 0.013 μM 25659731
Kasumi-1 Growth Inhibition Assay 72 h IC50=0.009 ± 0.0009 μM 25659731
HL-60 Growth Inhibition Assay 72?h IC50=0.3 nM 23618862
U937? Growth Inhibition Assay 72?h IC50=0.8 nM 23618862
DB Growth Inhibition Assay 48?h GI50=3.5 nM 21237508
Pfeiffer Growth Inhibition Assay 48?h GI50=3.9 nM 21237508
SU-DHL-5 Growth Inhibition Assay 48?h GI50=0.23 nM 21237508
SU-DHL-8 Growth Inhibition Assay 48?h GI50=1.4 nM 21237508
WSU-DLCL-2 Growth Inhibition Assay 48?h GI50=1.4 nM 21237508
RPMI-7951 Growth Inhibition Assay GI50=3.2 nM 21737502
SK-MEL-5 Growth Inhibition Assay GI50=4.2 nM 21737502
A375 Growth Inhibition Assay GI50=6.3 nM 21737502
SK-MEL-28 Growth Inhibition Assay GI50=7.6 nM 21737502
SK-MEL-2 Growth Inhibition Assay GI50=11 nM 21737502
A549 Growth inhibition assay Growth inhibition of human A549 cells, IC50=0.0134μM 28814374
DU145 Cytotoxicity assay Cytotoxicity against human DU145 cells by MTT assay, EC50=0.0138μM 28774426
PC3 Cytotoxicity assay Cytotoxicity against human PC3 cells by MTT assay, EC50=0.092μM 28774426
A549 Function assay Inhibition of PAK1 in human A549 cells, IC50=0.5μM 28814374
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生物活性

產(chǎn)品描述 Sepantronium Bromide(YM155)是一種有效的survivin抑制藥，通過(guò)抑制Survivin啟動(dòng)子活性而發(fā)揮作用，在HeLa-SURP-luc 和 CHO-SV40-luc細(xì)胞中IC50為0.54 nM；對(duì)SV40啟動(dòng)子活性抑制作用不顯著，能夠輕微抑制Survivin與XIAP相互作用。YM155 在乳腺癌細(xì)胞中可下調(diào) survivin 和 XIAP、調(diào)節(jié)自噬并誘導(dǎo)自噬依賴(lài)的DNA損傷。Phase 2。
靶點(diǎn)
Survivin [1]
(HeLa-SURP-luc, CHO-SV40-luc cells)
0.54 nM
體外研究(In Vitro)
體外研究活性

YM155 30 μM時(shí)對(duì)SV40作用效果也不大。在p53缺陷的PC-3和PPC-1 人類(lèi)HRPC細(xì)胞中，通過(guò)抑制 survivin基因啟動(dòng)子的轉(zhuǎn)錄，YM155顯著抑制內(nèi)源性survivin的表達(dá)。相反，YM155 100 nM時(shí)對(duì)c-IAP2, XIAP, Bcl-2, Bcl-xL, Bad, α-actin,及β-tubulin的蛋白表達(dá)仍沒(méi)抑制效果。YM155作用于人類(lèi)癌細(xì)胞系包括PC-3和PPC-1，使細(xì)胞發(fā)生凋亡，伴隨著caspase-3活性上升。YM155有效抑制人類(lèi)癌細(xì)胞系(突變p53或短小p53) 包括PC-3, PPC-1, DU145, TSU-Pr1, 22Rv1, SK-MEL-5及A375 ，IC50值為2.3到11 nM。[1]另外，YM155增強(qiáng)NSCLC細(xì)胞對(duì)γ-射線(xiàn)的敏感性。YM155和γ-射線(xiàn)聯(lián)用，增強(qiáng)凋亡細(xì)胞數(shù)和caspase-3活性。 YM155推遲修復(fù)放射誘導(dǎo)核DNA斷裂的雙鏈。[2]
激酶實(shí)驗(yàn) 啟動(dòng)子-熒光酶素報(bào)告實(shí)驗(yàn)
使用Pyrobest聚合酶和引物5’-GCGCGCTCGAGTCTAGACATGCGGATATATTC-3’和5’-GCGCGAA-GCTTTGGCGGTTAATGGCGCGC-3’， 從人類(lèi)基因組DNA中分離2767個(gè)堿基對(duì)序列的人類(lèi)survivin基因啟動(dòng)子。在pGL3-Basic質(zhì)粒的XhoI/HindIII切除位點(diǎn)，內(nèi)切酶XhoI/HindIII切除產(chǎn)生的PCR片段。產(chǎn)生的質(zhì)粒稱(chēng)為pSUR-luc。通過(guò)DNA測(cè)序儀在所有增強(qiáng)序列處測(cè)定DNA序列。通過(guò)熒光酶素實(shí)驗(yàn)，使用短暫轉(zhuǎn)染的HeLa-S3細(xì)胞，測(cè)定pSUR-luc的活力。使用的pGL3質(zhì)粒含有SV40啟動(dòng)子和增強(qiáng)子序列。 pSUR-luc和pSV2bsr 質(zhì)粒通過(guò)Lipofectamin2000穩(wěn)定轉(zhuǎn)染到HeLa細(xì)胞中。加入10 μg/mL滅瘟素，根據(jù)適當(dāng)?shù)臒晒饷杆匦盘?hào)和基因穩(wěn)定性，篩選HeLa-SURP-luc單一群落。pGL3和pSV2bsr質(zhì)粒穩(wěn)定轉(zhuǎn)染到CHO細(xì)胞中。加入10 μg/mL滅瘟素，根據(jù)適當(dāng)?shù)臒晒饷杆匦盘?hào)和基因穩(wěn)定性，篩選CHO-SV40-luc單一群落。從HeLa-SURP-luc和CHO-SV40-luc群落中獲得細(xì)胞用于化學(xué)篩選。細(xì)胞按每孔5×103接種在96孔板上，加入YM155（溶于DMSO中）。24小時(shí)后測(cè)定熒光酶素活性。通過(guò)回歸分析計(jì)算IC50值。
細(xì)胞實(shí)驗(yàn) 細(xì)胞系 PC-3, PPC-1, DU145, TSU-Pr1, 22Rv1, SK-MEL-5，和A375細(xì)胞
濃度 ~ 100 nM
孵育時(shí)間 48小時(shí)
方法

PC-3, PPC-1, DU145, TSU-Pr1, 22Rv1, SK-MEL-5，及A375細(xì)胞系按5到40×103密度接種在96孔板上。YM155溶解在DMSO中，持續(xù)處理細(xì)胞48小時(shí)。通過(guò)sulforhodamine B試劑測(cè)定細(xì)胞數(shù)。
實(shí)驗(yàn)圖片 檢測(cè)方法 檢測(cè)指標(biāo) 實(shí)驗(yàn)圖片 PMID
Western blot p-STAT3 / STAT3 β-catenin / c-Myc / Cyclin D1 / CD44 Survivin / XIAP / Caspase-7 / Caspase-9 / Caspase-3 / Cleaved Caspase-8 / PARP 22723871
Immunofluorescence PARP-1 / PAR EGFR 26090615
Growth inhibition assay Cell viability 29636860
體內(nèi)研究(In Vivo)
體內(nèi)研究活性

YM155按3和10 mg/kg皮下注射前列腺移植瘤，結(jié)果顯示YM155完全抑制PC-3的腫瘤生長(zhǎng)，但是重量沒(méi)有降低，血細(xì)胞數(shù)也沒(méi)有下降。藥物動(dòng)力學(xué)分析顯示YM155作用于腫瘤組織效果很明顯。而且，YM155按5 mg/kg作用于PC-3常位移植瘤時(shí)腫瘤抑制率達(dá)80% 。[1]YM155和γ-射線(xiàn)聯(lián)用作用于攜帶H460或Calu6 移植瘤的裸鼠，顯示出強(qiáng)抗癌活性。[2]
動(dòng)物實(shí)驗(yàn) Animal Models 皮下注射PC-3移植瘤的雄性裸鼠(BALB/c nu/nu)
Dosages 5 mg/kg
Administration 皮下注射，每周持續(xù)處理3天，處理3周。
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05263583 Recruiting
High-grade B-cell Lymphoma|Burkitt Lymphoma|Lymphoma B-Cell|Lymphoma Large B-Cell Diffuse|Lymphatic Diseases|Lymphoma High-Grade|C-MYC/BCL2 Double-Hit High-Grade B-Cell Lymphoma|C-MYC/BCL6 Double-Hit High-Grade B-Cell Lymphoma|C-Myc Gene Rearrangement
Cothera Bioscience Inc
 December 9 2022 Phase 2
NCT01023386 Completed
Cancer
Astellas Pharma Inc
 November 2009 Phase 1

化學(xué)信息&溶解度

分子量 443.29 分子式

C20H19BrN4O3
CAS號(hào) 781661-94-7 SDF Download Sepantronium Bromide (YM155) SDF
Smiles CC1=[N+](C2=C(N1CCOC)C(=O)C3=CC=CC=C3C2=O)CC4=NC=CN=C4.[Br-]
儲(chǔ)存條件(自收到貨起)

體外溶解度
批次：

Water : 89 mg/mL (200.77 mM)

DMSO : 55 mg/mL ( (124.07 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Ethanol : 6 mg/mL (13.53 mM)

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

 動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量 濃度 體積 分子量

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

mg/kg g μL 只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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