| Identification | Back Directory | [Name]
BIO | [CAS]
667463-62-9 | [Synonyms]
Z E
6BIO
CS-1934
MLS2052
GSK 3 IX
MLS 2052
BIO USP/EP/BP
BIO (SM04554)
GSK3 Inhibitor IX1
BIO(GSK-3 Inhibitor IX
6-bromoindirubin-3-oxime
GSK-3 Inhibitor IX (BIO)
MLS-2052 (GSK-3 Inhibitor IX
InSolution? GSK-3 Inhibitor IX
GSK 3 Inhibitor IX (MLS 2052,6BIO)
(2'Z,3'E)-6-Bromoindirubin-3'-oxim
(2'Z,3'E)-6-Bromoindirubin-3'-oxime >
GSK 3 Inhibitor IX (6-Bromoindirubin-3'-oxime
GSK-3 Inhibitor IX - CAS 667463-62-9 - Calbiochem
GSK 3 INHIBITOR IX (6-BROMOINDIRUBIN-3'-OXIME; BIO)
BIO - GSK-3 inhibitor IX | 6-Bromoindirubin-3'-oxime
InSolution GSK-3 Inhibitor IX - CAS 667463-62-9 - Calbiochem
(2E,3E)-6'-Bromo-3-(hydroxyimino)-[2,3'-biindolinylidene]-2'-one
6BIO;6-BIO;GSK 3 IX;GSK 3 INHIBITOR IX;MLS 2052;MLS2052;GSK-3 INHIBITOR IX; 6-BROMOINDIRUBIN-3-OXIME
2H-Indol-2-one, 6-broMo-3-[(3E)-1,3-dihydro-3-(hydroxyiMino)-2H-indol-2-ylidene]-1,3-dihydro-, (3Z)- | [Molecular Formula]
C16H10BrN3O2 | [MDL Number]
MFCD08705318 | [MOL File]
667463-62-9.mol | [Molecular Weight]
356.178 |
| Chemical Properties | Back Directory | [Melting point ]
300°C(lit.) | [Boiling point ]
554.3±50.0 °C(Predicted) | [density ]
1.80±0.1 g/cm3(Predicted) | [RTECS ]
NM3241900 | [storage temp. ]
2-8°C
| [solubility ]
DMSO: >5 mg/mL
| [form ]
solid
| [pka]
9.56±0.20(Predicted) | [color ]
dark red
| [Sensitive ]
Air & Light Sensitive | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months. |
| Hazard Information | Back Directory | [Description]
BIO is a cell-permeable bis-indolo (indirubin) compound that acts as a highly potent, selective, reversible, and ATP-competitive inhibitor of GSK3α/β (IC50 = 5 nM). 1,2 Its specificity has been tested against various cyclin-dependent kinases (CDKs) (IC50s = 83, 300, 320, and 10,000 nM for Cdk5/p25, Cdk2/A, Cdk1/B, and Cdk4/D1, respectively). BIO was also tested for its specificity towards many other commonly studied kinases (IC50 ≥10 μM), including MAP kinases, PKA, PKC isoforms, PKG, CK, and IRTK. 1,2 Inhibition of GSK by BIO has been shown to result in the activation of the Wnt signaling pathway and sustained pluripotency in human and mouse embryonic stem cells (ESCs).3 BIO is reported to maintain self-renewal in human and mouse ESCs as well as induce the differentiation of neonatal cardiomyocytes.4 | [Uses]
Inhibitor of phosphoinositide-dependent kinase 1 (PDK1). Potent, reversible and ATP-competitive inhibitor of glycogen synthase kinase-3α/β (GSK-3α/β) (IC50=5nM). Maintains self-renewal and pluripotency in embryonic stem cells via activation of Wnt in vitro. Promotes proliferation and dedifferentiation in cardiomyocytes. | [Definition]
ChEBI: 6-bromoindirubin-3'-oxime is a member of the class of biindoles that is indirubin substituted at position 6 by a bromo group and in which the keto group at position 3' has undergone condensation with hydroxylamine to form the corresponding oxime. It has a role as an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor and an EC 2.7.11.26 (tau-protein kinase) inhibitor. It is a ketoxime, an organobromine compound, a member of oxindoles and a biindole. | [General Description]
A cell-permeable, highly potent, selective, reversible, and ATP-competitive inhibitor of GSK-3α/β (IC50 = 5 nM). Specificity was confirmed using various Cdk′s (IC50 = 83 nM for Cdk5/p25, 300 nM for Cdk2/cyclin A, 320 nM for Cdk1/cyclin B, and 10 μM for Cdk4/cyclin D1), MAP kinases, PKA, PKC isoforms, PKG, CK, and IRTK (IC50 ≥ 10 μM). Inhibition of GSK by BIO has been shown to result in the activation of the Wnt signaling pathway and sustained pluripotency of human and murine embryonic stem cells (ESCs). | [Biological Activity]
Potent and selective, ATP-competitive glycogen synthase kinase-3 (GSK-3) inhibitor (IC 50 values are 5, 83, 300, 320 and > 10 000 nM at GSK-3, CDK5/p25, CDK2/cyclin A, CDK1/cyclin B and other common kinases respectively). Maintains self-renewal and pluripotency in embryonic stem cells via activation of the Wnt signaling pathway in vitro . | [Biochem/physiol Actions]
Cell permeable: yes | [Enzyme inhibitor]
These protein kinase inhibitors (FWBIO = 356.19 g/mol; CAS 667463-62-9;
Solubility: 70 mg/mL DMSO, <1mg/mL H2O), also known as BIO, 6BIO,
and systematically as 6-bromo-3-[ (3E) -1,3-dihydro-3- (hydroxyimino) -2H-
indol-2-ylidene]-1,3-dihydro- (3Z) -2H-indol-2-one, targets glycogen
synthase kinase-3 (or GSK-3), with an IC50 value of 5 nM for α and β forms.
BIO also shows greater than 16x selectivity over CDK5 and is also a weaker
pan-JAK inhibitor, with IC50 values of 30 nM, 1.5 μM, 8.0 μM, and 0.5 μM
for TYK2, JAK1, JAK2 and JAK3. (See the structural related inhibitor
1-Azakenpaullone) BIO, but not 1-methyl-BIO, closely mimicked Wnt
signaling in Xenopus embryos. BIO-induced apoptosis of human
melanoma cells is associated with reduced phosphorylation of JAKs and
STAT3 in both dose- and time-dependent manners. Consistent with
inhibition of STAT3 signaling, expression of the anti-apoptotic protein Mcl-
1 was down-regulated. Maintaining Embryonic Stem Cells Pluripotency:
Human and mouse embryonic stem cells (ESCs) self-renew indefinitely
while maintaining the ability to generate all three germ-layer derivatives.
Importantly, Wnt pathway activation by BIO is sufficient to maintain the
undifferentiated phenotype in both types of ESCs and sustains expression of
the pluripotent state-specific transcription factors Oct-3/4, Rex-1 and Nanog
. Such results suggest that BIO and related GSK-3-specific inhibitors may
off practical advantages in regenerative medicine. Bio can also participate in
controlling the proliferative capability of the highly differentiated
cardiomyocytes. Activation of Wnt/β-catenin and inhibition of Notch
signaling pathways, as mediated by simultaneous co-application of BIO and
the γ-secretase inhibitor N-[ (3,5-difluorophenyl) acetyl]-L-alanyl-2-
phenylglycine-1,1-dimethylethyl ester (or DAPT), efficiently induces
intestinal differentiation of ESCs cultured on feeder cells. These findings
that Wnt and Notch signaling function to pattern the anterior-posterior axis
of the DE and control intestinal differentiation. 6-Bromoindirubin-3'-
acetoxime: This cell-permeable BIO analogue (FW = 398.21
g/mol; CAS 667463-85-6) is active against herpes simplex virus-1 (HSV-1)
infection in human oral epithelial cells, the latter representing a natural
target cell type. BIO-acetoxime reduces viral yields and the expression of
different classes of viral proteins. BIO-acetoxime may suppress viral gene
expression and protect oral epithelial cells from HSV-1 infection. Tyrian
Purple: BIO’s indirubin nucleus is related to the famous Tyrian purple dye
that the Phoenicians isolated from the gastropod mollusk Hexaplex trunculus
and gained favor in antiquity, because it did not fade, actually becoming
more brilliant upon weathering and exposure to sunlight. The inhibitory
properties of BIO suggest that 6-bromoindirubin provides a new scaffold for
the development of selective and potent pharmacological inhibitors of GSK-
3. | [in vivo]
study showed bio activated maternal wnt signaling pathway in xenopus embryos. it caused a hyper dorso-anteriorization at the expense of trunk and tail in a dose-response manner. it also activated the dorsal genes (siamois and chordin) ectopically. [1] | [storage]
+4°C | [References]
1) Meijer et al. (2003), GSK-3-selective inhibitors derived from Tyrian purple indirubins; Chem. Biol., 10 1255
2) Tseng et al. (2006), The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes; Chem. Biol., 13 957
3) Chebel et al. (2009), Indirubin derivatives inhibit malignant lymphoid cell proliferation; Leuk. Lymphoma, 50 2049 |
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