GANT 58 (Synonyms: NSC 75503) |
| Catalog No.GC16789 |
An inhibitor of Gli transcription
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 64048-12-0
Sample solution is provided at 25 µL, 10mM.
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GANT 58 is an antagonist of GLI that inhibits GLI1-induced transcription with an IC50 value of 5 μM [1].
GLI1 is a human glioblastoma isolated protein which belongs to GLI protein family. GLI proteins act as effectors in Hedgehog signaling pathway and get involved in cell proliferation, determination and patterning during embryo development.
GANT 58 is considered to inhibit GLI1-mediated gene trans-activation with a high selectivity for Hedgehog signaling pathway. When TNF signaling/NFkB activation, glucocorticoid, receptor gene transactivation, and the Ras-Raf-Mek-Mapk cascade were treated with GANT 58, no inhibition was observed. When SAG-treated shh-L2 cells were treated with 10 μM GANT 58 for 48 hr, the reduction of Hedgehog pathway signaling was observed, whereas Gli1 mRNA level reduction was induced by the treatment of 10 μM GANT 58 for 2-3 days. Indeed, GANT 58 was confirmed as inhibitor of Hedgehog signaling pathway downstream Sufu and Smo [1]. Furthermore, GANT 58 treatments for 48 hr resulted in the significant reduction of cell viability in a dose-dependent manner for CCRFeCEM, CEM7e14, CEM1e15 and Jurkat cells. When CCRFeCEM cells were treated with 10 μM GANT 58 for 48 hr, the percentage of cells in G1/S phase increased whereas the percentage in G2/M phase decreased [2].
In mouse model with xenograft, daily s.c. injection of GANT 58 resulted in significant suppression of tumor cell growth. 50 mg/kg/d GANT 58 injections for 18 days induced the suppression of additional xenograft growth and restrict the increase of tumor size. No side effects were observed during the treatment [1].
References:
[1] Lauth M, Bergstr?m ?sa, Shimokawa T, Toftg?rd R. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists.?Proceedings of the National Academy of Sciences of the United States of America. 2007,104(20):8455-8460.
[2] Hou X, Chen X, Zhang P, et al. Inhibition of hedgehog signaling by GANT58 induces apoptosis and shows synergistic antitumor activity with AKT inhibitor in acute T cell leukemia cells. Biochimie. 2014, 101:50-9
Cell experiment: | HEK293 cells are transfected with GLI1 expression plasmid, together with the reporter plasmids 12× GliBS-Luc 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. Plates are read on a Berthold Technologies microplate luminometer. 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. Samples are read on a Molecular Devices SpectraMax Gemini EM[1]. |
Animal experiment: | Mice[1] 5×106 22Rv1 cells are suspended in a total volume of 100 μL of a 1:1 mixture of RPMI medium 1640:Matrigel (E1270). The cell suspension is injected s.c. at the posterior flank of female BALB/c nude mice (nu/nu). Tumors are grown until they reached a median size of ≈250 mm3 (5-6 days). Animals are randomly divided into four groups (n=4-5) and treated with solvent only (corn oil:ethanol, 4:1) or compounds in solvent (50 mg/kg) for 16 days s.c. injections of compounds are performed several centimeters away from the tumor. Tumor volumes are calculated by the formula length×width×0.5×(length+width). At the end of the treatment period, animals are given a BrdU pulse (50 mg/kg) for 30 min, and tumors are removed. All animal experiments are approved by local ethics authorities. |
References: [1]. Lauth M, et al. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8455-60. | |
| Cas No. | 64048-12-0 | SDF | |
| Synonyms | NSC 75503 | ||
| Chemical Name | 4-(2,4,5-tripyridin-4-ylthiophen-3-yl)pyridine | ||
| Canonical SMILES | C1=CN=CC=C1C2=C(SC(=C2C3=CC=NC=C3)C4=CC=NC=C4)C5=CC=NC=C5 | ||
| Formula | C24H16N4S | M.Wt | 392.48 |
| Solubility | ≥ 18.95 mg/mL in DMSO, ≥ 14.9 mg/mL in EtOH with ultrasonic and warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.5479 mL | 12.7395 mL | 25.479 mL |
| 5 mM | 0.5096 mL | 2.5479 mL | 5.0958 mL |
| 10 mM | 0.2548 mL | 1.274 mL | 2.5479 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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- Purity: >99.50%
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