BIO

BIO (GSK-3 Inhibitor IX, 6-bromoindirubin-3-oxime, 6-Bromoindirubin-3'-oxime, MLS 2052) is a specific inhibitor of GSK-3 with IC50 of 5 nM for GSK-3α/β in a cell-free assay, shows >16-fold selectivity over CDK5, also a pan-JAK inhibitor with IC50 of 30 nM for Tyk2. BIO induces apoptosis in human melanoma cells.

CAS No. 667463-62-9

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
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（32）

製品安全説明書

現在のバッチを見る：純度： 99.93%

99.93

BIO関連製品

関連ターゲット	GSK-3α GSK-3β	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library Apoptosis Compound Library Cell Cycle compound library NF-κB Signaling Compound Library	もっと見る

シグナル伝達経路

GSK-3シグナル伝達経路

GSK-3阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
A549	Function assay	10 uM	15 mins	Inhibition of human mPGES1 from human A549 cells assessed as PGE2 at 10 uM after 15 mins by HPLC	24697244
HT22	Function assay	10 uM	24 hrs	Inhibition of GSK3-mediated beta casein phosphorylation in mouse HT22 cells at 10 uM after 24 hrs by Western blot analysis in presence of MG132	22998443
HEK293	Function assay	0.5 to 1 uM		Inhibition of human GSK3 activity in HEK293 cells containing the Wnt/beta-catenin activated reporter pSuperTOPFLASH (STF293 cells) at 0.5 to 1 uM by Wnt reporter gene assay	24697244
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST-tagged CDK4 (S4 to E303 residues)/Cyclin D1 (Q4 to I295 residues) expressed in sf9 cells at 1 uM using RB-CTF as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST/His6-tagged GSK3beta (M1 to T420 residues) expressed in baculovirus infected sf9 cells at 1 uM using RBER-IRStide as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST-tagged CDK2 (M1 to L298 residues)/Cyclin A2 (M1 to L432 residues) expressed in baculovirus infected sf9 cells at 1 uM using Histone H1 as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST-tagged CDK5 (M1 to P292 residues)/p35NCK (M1 to R307 residues) expressed in baculovirus infected sf9 cells at 1 uM using RB-CTF as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST/His6-tagged Aurora B (A2 to A344 residues) expressed in sf9 cells at 1 uM using tetra(LRRLSLG) as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST/His6-tagged FGFR1 (G400 to R820 residues) expressed in baculovirus infected sf9 cells at 1 uM using Poly(Glu,Tyr)4:1 as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST/His6-tagged CDK1 (M1 to M297 residues)/Cyclin B1 (M1 to V433 residues) expressed in sf9 cells at 1 uM using RB-CTF as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST-tagged CDK2 (M1 to L298 residues)/Cyclin E1 (M1 to A395 residues) expressed in sf9 cells at 1 uM using RB-CTF as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST/His6-tagged Aurora A (M1 to S403 residues) expressed in baculovirus infected sf9 cells at 1 uM using tetra(LRRLSLG) as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST-tagged Aurora B (M1 to S27 residues) expressed in sf9 cells at 1 uM using CDC25C-derived peptide as substrate by filter binding assay	28557430
HuH7	Antiproliferative assay		72 hrs	Antiproliferative activity against human HuH7 cells after 72 hrs by MTT assay, IC50 = 6.2 μM.	19783149
HL60	Antiproliferative assay		5 days	Antiproliferative activity against human HL60 cells after 5 days by MTT assay, IC50 = 5.4 μM.	19783149
HepG2	Cytotoxicity assay		24 hrs	Cytotoxicity against human HepG2 cells assessed as cell growth inhibition after 24 hrs by alamar blue assay, IC50 = 5.3 μM.	28743492
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by MTT assay, IC50 = 5.2 μM.	19783149
IMR90	Antiproliferative assay		72 hrs	Antiproliferative activity against human IMR90 cells after 72 hrs by MTT assay, IC50 = 1.9 μM.	19783149
K562	Antiproliferative assay		72 hrs	Antiproliferative activity against human K562 cells after 72 hrs by MTT assay, IC50 = 1.3 μM.	19783149
SH-SY5Y	Cytotoxicity assay		48 hrs	Cytotoxicity against human SH-SY5Y cells after 48 hrs by MTS reduction assay, IC50 = 9 μM.	18816110
SH-SY5Y	Function assay		48 hrs	Survival of human SH-SY5Y cells after 48 hrs by MTS reduction assay, IC50 = 9.5 μM.	16854069
SH-SY5Y	Function assay		24 hrs	Survival of human SH-SY5Y cells after 24 hrs by MTS reduction assay, IC50 = 18 μM.	16854069
IMR32	Cytotoxicity assay		48 hrs	Cytotoxicity against human IMR32 cells assessed as cell viability after 48 hrs by MTT assay	21802947
SK-N-SH	Cytotoxicity assay		48 hrs	Cytotoxicity against human SK-N-SH cells assessed as cell viability after 48 hrs by MTT assay	21802947
NB39	Cytotoxicity assay		48 hrs	Cytotoxicity against human NB39 cells assessed as cell viability after 48 hrs by MTT assay	21802947
SH-SY5Y	Function assay			Inhibition of GSK3-mediated beta-casein phosphorylation in human SH-SY5Y cells in presence of MG132 by Western blot analysis, IC50 = 0.29 μM.	18816110
HEI-OC1	Function assay			Protection against cisplatin-induced cell death in neonatal mouse HEI-OC1 cells assessed as reduction in caspase-3/7 activity, EC50 = 0.192 μM.	30091915
SH-SY5Y	Function assay			Death of human SH-SY5Y cells in absence of 20 uM Q-VD-OPh by MTS reduction assay, IC50 = 10 μM.	16854069
SH-SY5Y	Function assay			Death of human SH-SY5Y cells in presence of 20 uM Q-VD-OPh by MTS reduction assay, IC50 = 13 μM.	16854069
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 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
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

BIO (GSK-3 Inhibitor IX, 6-bromoindirubin-3-oxime, 6-Bromoindirubin-3'-oxime, MLS 2052) is a specific inhibitor of GSK-3 with IC50 of 5 nM for GSK-3α/β in a cell-free assay, shows >16-fold selectivity over CDK5, also a pan-JAK inhibitor with IC50 of 30 nM for Tyk2. BIO induces apoptosis in human melanoma cells.

特性

The first pharmacological agent shown to maintain self-renewal in human and mouse embryonic stem cells.

Targets

GSK-3 ^[1] (Cell-free assay)	TYK2 ^[4] (Cell-free assay)	CDK5/p35 ^[1] (Cell-free assay)	CDK2/CyclinA ^[1] (Cell-free assay)	CDK1/CyclinB ^[1] (Cell-free assay)	もっとクリックする
5 nM	30 nM	0.08 μM	0.30 μM	0.32 μM	もっとクリックする

In Vitro
In vitro	BIO (6-bromoindirubin-3'-oxime) is a specific inhibitor of glycogen synthase kinase-3 (GSK-3), with IC50 of 5 nM for GSK-3α/β, shows >16-fold selectivity over CDK5. BIO interacts within the ATP binding pocket of these kinases, reduces β-catenin phosphorylation on a GSK-3-specific site in cellular models, closely mimicks Wnt signaling in Xenopus embryos. ^[1] In human and mouse embryonic stem cells, BIO maintains the undifferentiated phenotype and sustains expression of the pluripotent state-specific transcription factors Oct-3/4, Rex-1 and Nanog. BIO-mediated Wnt activation is functionally reversible, as withdrawal of the compound leads to normal multidifferentiation programs in both human and mouse embryonic stem cells. ^[2] BIO promotes proliferation in mammalian cardiomyocytes. ^[3]6BIO is also a pan-JAK inhibitor, with IC50 values of 0.03, 1.5, 8.0, 0.5 μM for TYK2, JAK1, JAK2 and JAK3. BIO selectively inhibits phosphorylation of STAT3 and induces apoptosis of human melanoma cells. ^[4]
Kinase Assay	Kinase assay
Kinase Assay	Kinase activities are assayed in Buffer A or C at 30°C, at a final ATP concentration of 15 μM. Blank values are subtracted and activities calculated as pmoles of phosphate incorporated during a 10 min incubation. Controls are performed with appropriate dilutions of dimethylsulfoxide. In a few cases phosphorylation of the substrate is assessed by autoradiography after SDS-PAGE. GSK-3α/β is purified from porcine brain by affinity chromatography on immobilized axin. It is assayed, following a 1/100 dilution in 1 mg BSA/ml 10 mM DTT, with 5 μl 40 μM GS-1 peptide, a specific GSK-3 substrate, (YRRAAVPPSPSLSRHSSPHQSpEDEEE), in buffer A, in the presence of 15 μM [γ-³²P] ATP (3,000 Ci/mmol; 1 mCi/ml) in a final volume of 30 μl. After 30 min incubation at 30°C, 25 μl aliquots of supernatant are spotted onto 2.5 × 3 cm pieces of Whatman P81 phosphocellulose paper, and 20 seconds later, the filters are washed five times (for at least 5 min each time) in a solution of 10 ml phosphoric acid/liter of water. The wet filters are counted in the presence of 1 ml ACS scintillation fluid.
細胞実験	細胞株	COS1, Hepa or SH-SY5Y cells
	濃度	~10 μM
	反応時間	12 or 24 h
	実験の流れ	COS1, Hepa (wild-type, CEM/LM AhR deficient and ELB1 ARNT deficient), or SH-SY5Y cells are grown in 6 cm culture dishes in Dulbecco's Modified Medium (DMEM) containing 10% fetal bovine serum. For treatment, IO (5 μM), BIO (5 or 10 μM), MeBIO (5 or 50 μM), LiCl (20 or 40 mM), or mock solution (DMSO, 0.5% final concentration) is added to medium when cell density reaches ∼70% confluence. After 12 (SH-SY5Y) or 24 hours, the cells, while still in plate, are lysed with lysis buffer (1% SDS, 1 mM sodium orthovanadate, 10 mM Tris [pH 7.4]). The lysate is passed several times through a 26G needle, centrifuged at 10,000 × g for 5 min, and adjusted to equal protein concentration. About 8 μg of each sample is loaded for immunoblotting. Enhanced chemiluminescence is used for detection. The following primary antibodies are used: mouse anti-β-catenin CT (Upstate Biotechnolgies, Clone 7D8, recognizes total β-catenin), mouse anti-phospho-β-catenin (Upstate Biotechnologies, Clone 8E7, recognizes dephosphorylated β-catenin), mouse anti-GSK-3 β, mouse anti-GSK-3 phosphoTyr216, rabbit anti-AhR (Aryl hydrocarbon receptor), and rabbit anti-actin.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-AKT / AKT / p21 / p27 p-β-catenin / β-catenin FoxO3a / FoxO1 / p-FoxO3a / p-FoxO1		27510556
	Immunofluorescence	pAKT / p21 / p27 TNF-α E-cadherin / Nanog Oct3/4		27510556
	Growth inhibition assay	Cell proliferation		27510556

In Vivo
In Vivo	BIO suppresses melanoma tumor growth in a mouse xenograft model. ^[4]
動物実験	動物モデル	mouse
	投与量	50 mg/kg
	投与経路	Oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT06150287	Not yet recruiting	Renal Transplantation	State University of New York - Upstate Medical University	February 2024	Early Phase 1

参考
[1] Meijer L, et al. Chem Biol, 2003, 10(12), 1255-1266. [2] Sato N, et al. Nat Med, 2004, 10(1), 55-63. [3] Tseng AS, et al. Chem Biol, 2006, 13(9), 957-963. [4] Liu L, et al. Cancer Res. 2011 Jun 1;71(11):3972-3279. + 展開

参考

[4] Liu L, et al. Cancer Res. 2011 Jun 1;71(11):3972-3279.

+ 展開

化学情報

分子量	356.17	化学式	C₁₆H₁₀BrN₃O₂
CAS No.	667463-62-9	SDF	Download BIO SDFをダウンロードする
Smiles	C1=CC=C2C(=C1)C(=C(N2)C3=C(NC4=C3C=CC(=C4)Br)O)N=O
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:

DMSO : 71 mg/mL ( (199.34 mM)；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。)

Ethanol : 7 mg/mL

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):