GANT61

GANT61 (NSC 136476) is an inhibitor for GLI1 as well as GLI2-induced transcription, inhibits hedgehog with IC50 of 5 μM in GLI1 expressing HEK293T cell, displays selectivity over other pathways, such as TNF and glucocorticoid receptor gene transactivation. GANT61 induces apoptosis and activates protective autophagy in LX-2 cells.

CAS No. 500579-04-4

サイズ	価格(税別)	在庫状況
10mg	JPY 22000	国内在庫あり
50mg	JPY 85500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（95）

製品安全説明書

GANT61関連製品

関連ターゲット	Hedgehog Smoothened GLI	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Stem Cell Signaling Compound Library GPCR Compound Library Stem Cell Differentiation Compound Library	もっと見る

シグナル伝達経路

Hedgehog/Smoothenedシグナル伝達経路

Hedgehog/Smoothened阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
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

製品説明

GANT61 (NSC 136476) is an inhibitor for GLI1 as well as GLI2-induced transcription, inhibits hedgehog with IC50 of 5 μM in GLI1 expressing HEK293T cell, displays selectivity over other pathways, such as TNF and glucocorticoid receptor gene transactivation. GANT61 induces apoptosis and activates protective autophagy in LX-2 cells.

Targets

GLI1 ^[1]
(HEK293T cells expressing GLI1)

5 μM

In Vitro
In vitro	GANT61 is an inhibitor for GLI1 as well as GLI2-induced transcription. GANT61 inhibits the DNA binding ability of GLI1. GANT61 inhibits hedgehog signaling with IC50 of 5 μM, displays selectivity over other pathways, such as TNF signaling/NFκB activation, glucocorticoid receptor gene transactivation, and the Ras–Raf–Mek–Mapk cascade. GANT61 efficiently inhibited in vitro tumor cell proliferation in a GLI-dependent manner. ^[1] GANT61 induces apoptosis in chronic lymphocytic leukemia cells (CLL), but not in normal B lymphocytes. ^[2] GANT61 induces robust cytotoxicity and abolishs the clonogenicity in human colon carcinoma cell lines. ^[3] GANT61 induces inhibition of DNA replication in early S-phase in human colon carcinoma cell lines, leading to DNA damage signaling involving an ATM–Chk2 axis and induction of cell death. ^[4] GANT61 (30 μM) causes growth arrest and apoptosis in acute myeloid leukemia (AML) cells. ^[5]
Kinase Assay	Dual Luciferase Assay
Kinase Assay	HEK293 cells are transfected with GLI1 expression plasmid, together with the reporter plasmids 12×GliBSLuc and R-Luc on 10-cm plates (day 0). Twenty-four hours later, cells are seeded in white 96-well plates with clear bottom at a density of 15,000 cells per well. Cells are allowed to attach, and compounds are added at a final concentration of 10 μM in DMSO (0.5% final DMSO concentration) (day 1.5). Cells are grown for another 24 h, subsequently lysed, and then analyzed by using the Dual Luciferase kit.
細胞実験	細胞株	PANC1 or 22Rv1
	濃度	~5 μM
	反応時間	48 h
	実験の流れ	BrdU Incorporation Assay. Subconfluent cells are grown in reduced FBS (2.5%) for 48 h in the presence of 5 μM test compound (or DMSO) on white 96-well plates with clear bottom. Subsequently, cells are labeled for 2 h with BrdU, fixed, and analyzed.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	GLI1 / p-STAT3 / STAT3 / SOCS3 GLI2 / Bcl-2		27275540
	Immunofluorescence	Gli2		24533083
	Growth inhibition assay	Cell viability		27275540

In Vivo
In Vivo	In nude mice injected with GLI1-positive 22Rv1 prostate cancer cells, GANT61 induces growth regression until no tumor is palpable. ^[1] In nude mice carrying SK-N-AS neuroblastoma xenografts, GANT61 treatment (oral gavage, 50 mg/kg) significantly inhibits tumor growth at Day 12 , as the tumor volume is reduced to 63% compared with controls. ^[6]
動物実験	動物モデル	BALB/c nude mice with 22Rv1 cell xenograft
	投与量	50 mg/kg
	投与経路	s.c.

参考
[1] Lauth M, et al. Proc Natl Acad Sci, 2007, 104(20), 8455-8560 [2] Desch P, et al. Oncogene, 2010, 29(35), 4885-4895. [3] Mazumdar Y, et al. Cancer Res, 2011, 71(3), 1092-1102. [4] Mazumdar T, et al. Cancer Res, 2011,71(17), 5904-5914. [5] Pan D, et al. Leuk Res, 2012, 36(6), 742-748. [6] Wickstorm M, et al. Int J Cancer, 2013, 132(7), 1516-1524. + 展開

参考

+ 展開

化学情報

分子量	429.6	化学式	C₂₇H₃₅N₅
CAS No.	500579-04-4	SDF	Download GANT61 SDFをダウンロードする
Smiles	CN(C)C1=CC=CC=C1CN2CCCN(C2C3=CC=NC=C3)CC4=CC=CC=C4N(C)C
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

Ethanol : 85 mg/mL

DMSO : Insoluble ( 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):