product name GANT61
Description: GANT61 (also known as NSC 136476) is a potent small-molecule inhibitor for GLI1 as well as GLI2-induced transcription, it inhibits hedgehog with IC50 of 5 μM in GLI1 expressing HEK293T cell, and also displays selectivity over other pathways, such as TNF and glucocorticoid receptor gene transactivation. GANT61 exerts its effect by preventing DNA binding. It has been demonstrated to induce cell death against Ewings sarcoma family tumor (ESFT) cell lines in a dose-dependent manner.
References: Proc Natl Acad Sci U S A. 2007 May 15;104(20):8455-60; Int J Cancer. 2013 Apr 1;132(7):1516-24.
429.6
Formula
C27H35N5
CAS No.
500579-04-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 12 mg/mL (27.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
5% DMSO+95% Corn oil: 30 mg/mL
Synonyms
NSC 136476
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19426189
| In Vitro |
In vitro activity: 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. GANT61 induces apoptosis in chronic lymphocytic leukemia cells (CLL), but not in normal B lymphocytes. GANT61 induces robust cytotoxicity and abolishs the clonogenicity in human colon carcinoma cell lines. 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. GANT61 (30 μM) causes growth arrest and apoptosis in acute myeloid leukemia (AML) cells. Kinase 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: 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. |
|---|---|
| In Vivo | In nude mice injected with GLI1-positive 22Rv1 prostate cancer cells, GANT61 induces growth regression until no tumor is palpable. 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. |
| Animal model | BALB/c nude mice with 22Rv1 cell xenograft |
| Formulation & Dosage | Dissolved in corn oil:ethanol,4:1; 50 mg/kg; s.c. administration |
| References | Proc Natl Acad Sci U S A. 2007 May 15;104(20):8455-60; Int J Cancer. 2013 Apr 1;132(7):1516-24. |
