Home Stem Cells & Wnt Hedgehog/Smoothened inhibitor - Apoptosis related activator - Autophagy activator GANT61 For research use only.

GANT61

Synonyms: NSC 136476

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.

GANT61 Chemical Structure

GANT61 Chemical Structure

CAS No. 500579-04-4

Purity & Quality Control

GANT61 Related Products

Signaling Pathway

Hedgehog/Smoothened Signaling Pathways

Hedgehog/Smoothened Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Shh Light2 Function assay Inhibition of SHH in mouse Shh Light2 cells by GLI-responsive firefly luciferase reporter gene assay, IC50 = 5 μM. 19309080
Shh-L2 Function assay Inhibition of Hedgehog signaling in human Shh-L2 cells, IC50 = 5 μM. 17494766
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
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
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
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
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
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
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
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
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
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
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
Click to View More Cell Line Experimental Data

Biological Activity

Description 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
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.
Cell Research Cell lines PANC1 or 22Rv1
Concentrations ~5 μM
Incubation Time 48 h
Method 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.
Experimental Result Images Methods Biomarkers Images 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]
Animal Research Animal Models BALB/c nude mice with 22Rv1 cell xenograft
Dosages 50 mg/kg
Administration s.c.

Chemical Information & Solubility

Molecular Weight 429.6 Formula

C27H35N5
CAS No. 500579-04-4 SDF Download GANT61 SDF
Smiles CN(C)C1=CC=CC=C1CN2CCCN(C2C3=CC=NC=C3)CC4=CC=CC=C4N(C)C
Storage (From the date of receipt)

In vitro
Batch:

Ethanol : 85 mg/mL

DMSO : Insoluble ( Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble


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