GANT61

製品コードS8075 バッチS807502

印刷

化学情報

Chemical Structure Synonyms NSC 136476 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H35N5
分子量 429.6 CAS No. 500579-04-4
Solubility (25°C)* 体外 Ethanol 85 mg/mL (197.85 mM)
DMSO Insoluble
Water Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 GANT61 (NSC 136476) は、GLI1 および GLI2誘導性転写の阻害剤であり、GLI1を発現するHEK293T細胞においてIC50 5 μMでhedgehogを阻害し、TNFや糖質コルチコイド受容体遺伝子転写活性化などの他の経路に対して選択性を示します。GANT61はLX-2細胞においてアポトーシスを誘導し、保護的なオートファジーを活性化します。
in vitro GANT61 is an inhibitor for GLI1 as well as GLI2-induced transcription. This compound inhibits the DNA binding ability of GLI1. It 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. This chemical efficiently inhibited in vitro tumor cell proliferation in a GLI-dependent manner. It induces apoptosis in chronic lymphocytic leukemia cells (CLL), but not in normal B lymphocytes. This compound induces robust cytotoxicity and abolishs the clonogenicity in human colon carcinoma cell lines. It 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. This chemical (30 μM) causes growth arrest and apoptosis in acute myeloid leukemia (AML) cells.
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, this compound treatment (oral gavage, 50 mg/kg) significantly inhibits tumor growth at Day 12 , as the tumor volume is reduced to 63% compared with controls.

プロトコル(参考用のみ)

キナーゼアッセイ 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 this compound is 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.
細胞アッセイ 細胞株 PANC1 or 22Rv1
濃度 ~5 μM
反応時間 48 h
実験の流れ 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.
動物実験 動物モデル BALB/c nude mice with 22Rv1 cell xenograft
投薬量 50 mg/kg
投与方法 s.c.

参考

  • https://pubmed.ncbi.nlm.nih.gov/17494766/
  • https://pubmed.ncbi.nlm.nih.gov/20603613/
  • https://pubmed.ncbi.nlm.nih.gov/21135115/
  • https://pubmed.ncbi.nlm.nih.gov/21747117/
  • https://pubmed.ncbi.nlm.nih.gov/22398221/
  • https://pubmed.ncbi.nlm.nih.gov/22949014/

カスタマーフィードバック

, , Oncogene, 2017, 36(13): 1849-1861

, , Oncotarget. 2017, 8(30):48701-48710

Data from [Data independently produced by , , Cell Physiol Biochem, 2016, 38(4):1288-302.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The O-glycosyltransferase C1GALT1 promotes EWSR1::FLI1 expression and is a therapeutic target for Ewing sarcoma [ Nat Commun, 2025, 16(1):1267] PubMed: 39894896
Endothelial cell-derived SDF-1α elicits stemness traits of glioblastoma via dual-regulation of GLI1 [ Theranostics, 2025, 15(18):9819-9837] PubMed: 41041071
GPR137-RAB8A activation promotes ovarian cancer development via the Hedgehog pathway [ J Exp Clin Cancer Res, 2025, 44(1):22] PubMed: 39856733
PlexinD1 is a driver and a therapeutic target in advanced prostate cancer [ EMBO Mol Med, 2025, 17(2):336-364] PubMed: 39748059
Sonic Hedgehog potentiates BMP9-induced osteogenic differentiation of mesenchymal stem cells [ Genes Dis, 2025, 12(3):101308] PubMed: 40070367
Impact of Hedgehog modulators on signaling pathways in primary murine and human hepatocytes in vitro: insights into liver metabolism [ Arch Toxicol, 2025, 99(3):1105-1116] PubMed: 39714734
Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells [ EBioMedicine, 2024, 101:105026] PubMed: 38417378
Inhibition of primary cilia-hedgehog signaling axis triggers autophagic cell death and suppresses malignant progression of VHL wild-type ccRCC [ Cell Death Dis, 2024, 15(10):739] PubMed: 39389955
Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer [ Acta Pharm Sin B, 2023, 13(6):2601-2612] PubMed: 37425067
The deubiquitinating enzyme USP44 suppresses hepatocellular carcinoma progression by inhibiting Hedgehog signaling and PDL1 expression [ Cell Death Dis, 2023, 14(12):830] PubMed: 38097536

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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