GANT61

Catalog No.S8075

GANT61 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.

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GANT61 Chemical Structure

GANT61 Chemical Structure
Molecular Weight: 429.6

Validation & Quality Control

Customer Product Validation(2)

Quality Control & MSDS

Product Information

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Product Description

Biological Activity

Description GANT61 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.
Targets GLI1 [1]
(HEK293T cells expressing GLI1)
IC50 5 μM
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]
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]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

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 Assay: [1]

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.

Animal Study: [1]

Animal Models BALB/c nude mice with 22Rv1 cell xenograft
Formulation corn oil:ethanol,4:1
Dosages 50 mg/kg
Administration s.c.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[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.

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Chemical Information

Download GANT61 SDF
Molecular Weight (MW) 429.6
Formula

C27H35N5

CAS No. 500579-04-4
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms NSC 136476
Solubility (25°C) * In vitro Ethanol 12 mg/mL (27.93 mM)
DMSO <1 mg/mL (<1 mM)
Water <1 mg/mL (<1 mM)
In vivo 5% DMSO+95% Corn oil 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name Benzenamine, 2,2'-[[dihydro-2-(4-pyridinyl)-1,3(2H,4H)-pyrimidinediyl]bis(methylene)]bis[N,N-dimethyl-

Customer Product Validation (2)


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Rating
Source Mol Cell Biochem, 2014, 396(1-2): 257-68. GANT61 purchased from Selleck
Method Caspase-Glo Assay
Cell Lines GBC cells
Concentrations 20 μM
Incubation Time 0-72 h
Results The figure indicates that Gant-61 caused a clear increase in the activity of the effector caspases-3/-7, whereas the signal of cyclopamine treated cells was in the range of the untreated controls. For cyclopamine, no significant changes in the cell cycle distribution could be found.

Click to enlarge
Rating
Source Mol Cell Biochem, 2014, 396(1-2): 257-68. GANT61 purchased from Selleck
Method Fluorescence Microscopy
Cell Lines GBC cells
Concentrations 20 μM
Incubation Time 0-72 h
Results Gant-61-treated cells displayed an approximate linear increase of fragmented nuclei of 20, 30 and 45 % after 24, 48 and 72 h after treatment, respectively. For cyclopamine, no significant changes in the cell cycle distribution could be found.

Tech Support

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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