GANT 58
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
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 392.48 |
| Cas No. | 64048-12-0 |
| Formula | C24H16N4S |
| Synonyms | NSC 75503;GANT58;GANT-58;NSC-75503 |
| Solubility | insoluble in H2O; ≥14.9 mg/mL in EtOH with gentle warming and ultrasonic; ≥18.95 mg/mL in DMSO |
| Chemical Name | 4-(2,4,5-tripyridin-4-ylthiophen-3-yl)pyridine |
| SDF | Download SDF |
| Canonical SMILES | C1=CN=CC=C1C2=C(SC(=C2C3=CC=NC=C3)C4=CC=NC=C4)C5=CC=NC=C5 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
Shh-L2 cells |
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Reaction Conditions |
10 μM GANT 58 |
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Applications |
When SAG-treated Shh-L2 cells were treated with 10 μM GANT 58 for 48 hours, the reduction of Hedgehog pathway signaling was observed. At the same concentration of 10 μM, GANT 58 treatment (2 ~ 3 days) also reduced Gli1 mRNA levels, which is indicative of strong pathway inhibition. |
| Animal experiment:[1] | |
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Animal models |
Nude mice injected subcutaneously with GLI1-positive 22Rv1 prostate cancer cells |
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Dosage form |
50 mg/kg Once daily by subcutaneous injection for 18 days |
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Applications |
For human prostate cancer xenografts, GANT 58 treatment resulted in the inhibition of additional xenograft growth and limited the increase in tumor size. Meanwhile, GANT 58 strongly reduced the expression levels of the target gene PTCH. No adverse side effects (e.g. weight loss and ulcerations) were observed during the 18-day treatment time. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Lauth M, Bergström A, Shimokawa T, et al. 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. |
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| Description | GANT 58 is an antagonist of GLI that inhibits GLI1-induced transcription with an IC50 value of 5 μM. | |||||
| Targets | GLI | |||||
| IC50 | 5 μM | |||||
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