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GANT61

別名: NSC 136476

GANT61 (NSC 136476)是一種GLI1及GLI2誘導(dǎo)的轉(zhuǎn)錄抑制劑，抑制hedgehog，在表達(dá)GLI1的HEK293T細(xì)胞中IC50為5 μM，選擇性作用于其他通路，如TNF和糖皮質(zhì)激素受體基因的轉(zhuǎn)錄。GANT61在LX-2細(xì)胞中可誘導(dǎo)凋亡并激活保護(hù)性自噬。

GANT61 Chemical Structure

GANT61 Chemical Structure

CAS: 500579-04-4

規(guī)格 價(jià)格 庫(kù)存 購(gòu)買(mǎi)數(shù)量
10mg 1215.87 現(xiàn)貨
50mg 4661.51 現(xiàn)貨
1g 24488.1 現(xiàn)貨
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GANT61相關(guān)產(chǎn)品

相關(guān)信號(hào)通路圖

Hedgehog/Smoothened Signaling Pathways

Hedgehog/Smoothened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
22Rv Antitumor assay 50 mg/kg 18 days Antitumor activity in GLI1 positive human 22Rv cells xenografted mouse model at 50 mg/kg, sc after 18 days 17494766
NIH3T3 Function assay 10 uM Inhibition of Hedgehog/Gli1 mediated transformation in mouse NIH3T3 cells at 10 uM 17494766
PANC1 Function assay 5 uM Reduction in GLI1 expression in human PANC1 cells at 5 uM 17494766
PANC1 Function assay 5 uM Reduction in PTCH expression in human PANC1 cells at 5 uM 17494766
22Rv Function assay 5 uM Reduction in GlI1 expression in human 22Rv cells at 5 uM 17494766
22Rv Function assay 5 uM Reduction in PTCH expression in human 22Rv cells at 5 uM 17494766
HEK293 Function assay 30 uM Inhibition of GLI (unknown origin) expressed in HEK293 cells assessed as reduction in GLI-mediated transcription at 30 uM 25581017
TM3 Function assay 48 hrs Inhibition of Hh signaling pathway in mouse TM3 cells assessed as downregulation of Gli1 gene expression after 48 hrs by luciferase reporter gene assay, EC50 = 9.27 μM. 26976215
HeLa Function assay 4.5 hrs Inhibition of Ebolavirus glycoprotein/matrix protein VP40 entry in human HeLa cells after 4.5 hrs beta-lactamase reporter assay, IC50 = 6.83 μM. 29624387
Rh30 Function assay 24 hrs Inhibition of human Gli1-mediated transcriptional activity in human Rh30 cells after 24 hrs by luciferase reporter gene assay, IC50 = 40 μM. 20605720
SK-N-DZ Cytotoxicity assay 72 hrs Cytotoxicity against human SK-N-DZ cells after 72 hrs by fluorometric microculture cytotoxicity assay, GI50 = 5.82 μM. ChEMBL
SK-N-SH Cytotoxicity assay 72 hrs Cytotoxicity against human SK-N-SH cells after 72 hrs by fluorometric microculture cytotoxicity assay, GI50 = 5.82 μM. ChEMBL
SK-N-FI Cytotoxicity assay 72 hrs Cytotoxicity against human SK-N-FI cells after 72 hrs by fluorometric microculture cytotoxicity assay, GI50 = 5.82 μM. ChEMBL
SK-N-AS Cytotoxicity assay 72 hrs Cytotoxicity against human SK-N-AS cells after 72 hrs by fluorometric microculture cytotoxicity assay, GI50 = 5.82 μM. ChEMBL
IMR32 Cytotoxicity assay 72 hrs Cytotoxicity against human IMR32 cells after 72 hrs by fluorometric microculture cytotoxicity assay, GI50 = 5.82 μM. ChEMBL
SK-N-BE(2) Cytotoxicity assay 72 hrs Cytotoxicity against human SK-N-BE(2) cells after 72 hrs by fluorometric microculture cytotoxicity assay, GI50 = 5.82 μM. ChEMBL
SH-SY5Y Cytotoxicity assay 72 hrs Cytotoxicity against human SH-SY5Y cells after 72 hrs by fluorometric microculture cytotoxicity assay, GI50 = 5.82 μM. ChEMBL
NIH 3T3 Function assay Inhibition of Hh signaling pathway in Shh-LIGHT2 incorporated mouse NIH 3T3 cells assessed as downregulation of Gli1 gene expression by luciferase reporter gene assay, EC50 = 5 μM. 26976215
Shh-L2 Function assay Inhibition of Hedgehog signaling in human Shh-L2 cells, IC50 = 5 μM. 17494766
Shh Light2 Function assay Inhibition of SHH in mouse Shh Light2 cells by GLI-responsive firefly luciferase reporter gene assay, IC50 = 5 μM. 19309080
HEK293 Function assay Reduction of GLI2 mediated transcription in HEK293 cells by luciferase reporter assay 17494766
NIH3T3 Function assay Inhibition of GLI1 induced hedgehog signaling in mouse NIH3T3 cells 17494766
HEK293 Function assay Inhibition of beta galactosidase in HEK293 cells 17494766
MEF Function assay Reduction in expression of Hedgehog target gene Hip1 in Sufu deficient mouse MEF cells 17494766
22Rv Function assay Reduction of expression of PTCH mRNA in human 22Rv cells 17494766
HEK293 Function assay Inhibition of nuclear accumulation of GLI mutant in HEK293 cells 17494766
HEK293 Function assay Inhibition of nuclear accumulation of wild type GLI in HEK293 cells 17494766
HEK293 Function assay Reduction of GLI1 mediated transcription in HEK293 cells by luciferase reporter assay 17494766
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
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生物活性

產(chǎn)品描述 GANT61 (NSC 136476)是一種GLI1及GLI2誘導(dǎo)的轉(zhuǎn)錄抑制劑，抑制hedgehog，在表達(dá)GLI1的HEK293T細(xì)胞中IC50為5 μM，選擇性作用于其他通路，如TNF和糖皮質(zhì)激素受體基因的轉(zhuǎn)錄。GANT61在LX-2細(xì)胞中可誘導(dǎo)凋亡并激活保護(hù)性自噬。
靶點(diǎn)
GLI1 [1]
(HEK293T cells expressing GLI1)
5 μM
體外研究(In Vitro)
體外研究活性 GANT61抑制GLI1及GLI2誘導(dǎo)的轉(zhuǎn)錄。GANT61抑制GLI1的DNA結(jié)合能力。GANT61抑制hedgehog信號(hào)，IC50為5 μM，比作用于其他通路選擇性高，如TNF信號(hào)/NFκB激活，糖皮質(zhì)激素受體基因轉(zhuǎn)錄，及Ras-Raf-Mek-Mapk級(jí)聯(lián)。GANT61在體外有效抑制腫瘤細(xì)胞增殖，這種作用存在GLI依賴性。[1]GANT61作用于慢性淋巴細(xì)胞性白血病細(xì)胞（CLL），而非正常的B淋巴細(xì)胞，誘導(dǎo)細(xì)胞凋亡。[2]GANT61作用于人結(jié)腸癌細(xì)胞系，具有強(qiáng)大的細(xì)胞毒性，且廢除集落生成。[3]GANT61作用于人結(jié)腸癌細(xì)胞系的早S期階段，抑制DNA復(fù)制，產(chǎn)生涉及ATM-Chk2信號(hào)軸的DNA損傷信號(hào)，且誘導(dǎo)細(xì)胞死亡。[4] GANT61 (30 μM)作用于急性髓系白血?。ˋML）細(xì)胞，導(dǎo)致生長(zhǎng)停滯和凋亡。[5]
激酶實(shí)驗(yàn) 雙熒光素酶含量
轉(zhuǎn)染GLI1表達(dá)質(zhì)粒的HEK293細(xì)胞與報(bào)告質(zhì)粒12×GliBSLuc 和R-Luc 一起置于10 cm板上（實(shí)驗(yàn)第0天）。24小時(shí)后，細(xì)胞接種按每孔15,000個(gè)細(xì)胞的密度接種在白色透明底的96孔板中。細(xì)胞粘附，加入溶于DMSO(DMSO終濃度為0.5% ) 的終濃度為10 μM的化合物加（實(shí)驗(yàn)第1.5天）。細(xì)胞再生長(zhǎng)24小時(shí)，隨后裂解，然后使用雙熒光素酶試劑盒進(jìn)行分析。
細(xì)胞實(shí)驗(yàn) 細(xì)胞系 PANC1 或 22Rv1
濃度 ~5 μM
孵育時(shí)間 48 小時(shí)
方法 進(jìn)行BrdU滲透實(shí)驗(yàn)。在有5 μM 實(shí)驗(yàn)化合物 (或 DMSO) 存在下，亞融合的細(xì)胞在含F(xiàn)BS(2.5%)的白色透明底的96孔板上生長(zhǎng)48小時(shí)。隨后，使用BrdU對(duì)細(xì)胞進(jìn)行標(biāo)記2小時(shí)，混合，然后分析。
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 GLI1 / p-STAT3 / STAT3 / SOCS3 GLI2 / Bcl-2 27275540
Immunofluorescence Gli2 24533083
Growth inhibition assay Cell viability 27275540
體內(nèi)研究(In Vivo)
體內(nèi)研究活性 GANT61處理注射GLI1-陽(yáng)性22Rv1前列腺癌細(xì)胞的裸鼠，誘導(dǎo)腫瘤生長(zhǎng)衰退，直到觀察不到明顯的腫瘤。[1]GANT61按50 mg/kg劑量口服飼喂處理攜帶SK-N-AS神經(jīng)母細(xì)胞瘤移植瘤的裸鼠，在實(shí)驗(yàn)第12天顯著抑制腫瘤生長(zhǎng)，與對(duì)照組相比，腫瘤體積減少63％。[6]
動(dòng)物實(shí)驗(yàn) Animal Models 攜帶22Rv1細(xì)胞移植瘤的BALB/c裸鼠
Dosages 50 mg/kg
Administration 皮下注射

化學(xué)信息&溶解度

分子量 429.6 分子式

C27H35N5
CAS號(hào) 500579-04-4 SDF Download GANT61 SDF
Smiles CN(C)C1=CC=CC=C1CN2CCCN(C2C3=CC=NC=C3)CC4=CC=CC=C4N(C)C
儲(chǔ)存條件(自收到貨起)

體外溶解度
批次：

Ethanol : 85 mg/mL (197.85 mM)

DMSO : Insoluble ( ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

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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