GANT61

Catalog No.S8075 Batch:S807502

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Technical Data

Formula

C27H35N5
Molecular Weight 429.6 CAS No. 500579-04-4
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description GANT61 (NSC 136476) is an inhibitor for GLI1 as well as GLI2-induced transcription, inhibits hedgehog with IC50 of 5 μM in GLI1 expressing HEK293T cell, displays selectivity over other pathways, such as TNF and glucocorticoid receptor gene transactivation. GANT61 induces apoptosis and activates protective autophagy in LX-2 cells.
Targets
GLI1 [1]
(HEK293T cells expressing GLI1)
5 μM
In vitro 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. [1] GANT61 induces apoptosis in chronic lymphocytic leukemia cells (CLL), but not in normal B lymphocytes. [2] GANT61 induces robust cytotoxicity and abolishs the clonogenicity in human colon carcinoma cell lines. [3] 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. [4] GANT61 (30 μM) causes growth arrest and apoptosis in acute myeloid leukemia (AML) cells. [5]
In vivo In nude mice injected with GLI1-positive 22Rv1 prostate cancer cells, GANT61 induces growth regression until no tumor is palpable. [1] 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. [6]

Protocol (from reference)

Kinase Assay:[1]
  • 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 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:[1]
  • Cell lines

    PANC1 or 22Rv1

  • Concentrations

    ~5 μM

  • Incubation Time

    48 h

  • Method

    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.
Animal Study:[1]
  • Animal Models

    BALB/c nude mice with 22Rv1 cell xenograft

  • Dosages

    50 mg/kg

  • Administration

    s.c.

Customer Product Validation

, , 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.]

Data from [Data independently produced by , , J Exp Clin Cancer Res, 2016, 35(1):184.]

Selleck's GANT61 has been cited by 99 publications

Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells [ EBioMedicine, 2024, 101:105026] PubMed: 38417378
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
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
GANT-61 induces cell cycle resting and autophagy by down-regulating RNAP III signal pathway and tRNA-Gly-CCC synthesis to combate chondrosarcoma [ Cell Death Dis, 2023, 14(7):461] PubMed: 37488121
The deubiquitinating enzyme USP44 suppresses hepatocellular carcinoma progression by inhibiting Hedgehog signaling and PDL1 expression [ Cell Death Dis, 2023, 14(12):830] PubMed: 38097536
GANT-61 induces cell cycle resting and autophagy by down-regulating RNAP III signal pathway and tRNA-Gly-CCC synthesis to combate chondrosarcoma [ Cell Death Dis, 2023, 14(7):461] PubMed: 37488121
Selective induction of human renal interstitial progenitor-like cell lineages from iPSCs reveals development of mesangial and EPO-producing cells [ Cell Rep, 2023, S2211-1247(23)01614-5] PubMed: 38237600
Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma [ Mol Cancer Ther, 2023, 22(3):343-356] PubMed: 36807728
Signaling Switching from Hedgehog-GLI to MAPK Signaling Potentially Serves as a Compensatory Mechanism in Melanoma Cell Lines Resistant to GANT-61 [ Biomedicines, 2023, 11(5)1353] PubMed: 37239024
The Hedgehog/GLI signaling pathway activates transcription of Slug (Snail2) in melanoma cells [ Oncol Rep, 2023, 49(4)75] PubMed: 36866769

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.