GANT61

• CAS: 500579-04-4
• Catalog Number: ACM500579044
• Category: Inhibitors
• Molecular Weight: 429.60
• Molecular Formula: C27H35N5
• Description: GANT61 is a small-molecule inhibitor of glioma-associated oncogene 1 (GLI1)- and GLI2-mediated transcription at the nuclear level that exerts its effect by preventing DNA binding. It has been demonstrated to induce cell death against Ewing's sarcoma family tumor (ESFT) cell lines in a dose-dependent manner.
• Synonyms: GANT61; GANT-61; GANT 61; NSC 136476
• IUPAC Name: 2,2'-((2-(pyridin-4-yl)dihydropyrimidine-1,3(2H,4H)-diyl)bis(methylene))bis(N,N-dimethylaniline)
• Canonical SMILES: CN(C)C1=CC=CC=C1CN2C(C3=CC=NC=C3)N(CC4=CC=CC=C4N(C)C)CCC2
• InChI: InChI=1S/C27H35N5/c1-29(2)25-12-7-5-10-23(25)20-31-18-9-19-32(27(31)22-14-16-28-17-15-22)21-24-11-6-8-13-26(24)30(3)4/h5-8,10-17,27H,9,18-21H2,1-4H3
• InChI Key: KVQOGDQTWWCZFX-UHFFFAOYSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: White to off-white solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: GANT 61 is an inhibitor of Gli1 and Gli2 targeting the Hedgehog/GLI pathway.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 75.49; H, 8.21; N, 16.30
• Exact Mass: 429.28925
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: In human colon carcinoma cells, treatment with the Gli small-molecule inhibitor GANT61 induces extensive cell death. GANT61 induced transient cellular accumulation at G(1)-S (24 hours) and in early S-phase (32 hours), with elevated p21(Cip1), cyclin E, and cyclin A in HT29 cells. GANT61 induced DNA damage within 24 hours, with the appearance of p-ATM and p-Chk2. Pharmacologic inhibition of Gli1 and Gli2 by GANT61 or genetic inhibition by transient transfection of the Gli3 repressor (Gli3R) downregulated Gli1 and Gli2 expression and induced γH2AX, PARP cleavage, caspase-3 activation, and cell death. GANT61 induced γH2AX nuclear foci, while transient transfection of Gli3R showed expression of Gli3R and γH2AX foci within the same nuclei in HT29, SW480, and HCT116. GANT61 specifically targeted Gli1 and Gli2 substantiated by specific inhibition of (i) direct binding of Gli1 and Gli2 to the promoters of target genes HIP1 and BCL-2, (ii) Gli-luciferase activity, and (iii) transcriptional activation of BCL-2. Taken together, these findings establish that inhibition of HH signaling at the level of the GLI genes downstream of Smo is critical in the induction of DNA damage in early S-phase, leading to cell death in human colon carcinoma cells.; Reference: Cancer Res. 2011 Sep 1;71(17):5904-14. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21747117/
• In Vivo Activity: The 20 mg/kg GANT61 treatment reduced the incidence of collagen-induced arthritis (CIA) and relieved the arthritis symptoms in CIA rats. The Bcl-2 was upregulated and the Bax was downregulated in the CIA rats synovium. The 10 mg/kg and 20 mg/kg GANT61 diminished the Bcl-2 expression, 20 mg/kg GANT61 increased the Bax and activated the Caspases3 in the CIA synovium. The proliferation of CIA-FLS was significantly higher and the apoptosis of the CIA-FLS was lower than that of the control group. The 10 mg/kg and 20 mg/kg GANT61 treatment can reduce cell proliferation and induce apoptosis by diminishing Bcl-2 and increasing the Bax in CIA-FLS.; Reference: J Orthop Sci. 2019 Mar;24(2):353-360. https://linkinghub.elsevier.com/retrieve/pii/S0949-2658(18)30248-3
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).