500579-04-4

500579-04-4 structure

Name: GANT 61
Chemical Name: 2-[[3-[[2-(dimethylamino)phenyl]methyl]-2-pyridin-4-yl-1,3-diazinan-1-yl]methyl]-N,N-dimethylaniline
CAS Number: 500579-04-4
Molecular Formula: C₂₇H₃₅N₅
Molecular Weight: 429.600
Catalog: Biochemical Inhibitor Stem Cells & Wnt Signaling Paths (Stem Cells & Wnt) Hedgehog/Smoothened Inhibitor
Create Date: 2017-09-26 21:11:52
Modify Date: 2024-01-02 18:39:46
GANT 61 is an inhibitor of Gli1 and Gli2 targeting the Hedgehog/GLI pathway.

Name	2-[[3-[[2-(dimethylamino)phenyl]methyl]-2-pyridin-4-yl-1,3-diazinan-1-yl]methyl]-N,N-dimethylaniline
Synonyms	gant61 Benzenamine, 2,2'-[[dihydro-2-(4-pyridinyl)-1,3(2H,4H)-pyrimidinediyl]bis(methylene)]bis[N,N-dimethyl- 2,2'-{[2-(4-Pyridinyl)dihydropyrimidine-1,3(2H,4H)-diyl]bis(methylene)}bis(N,N-dimethylaniline) 2-((3-(2-(dimethylamino)benzyl)-2-(4-pyridinyl)tetrahydro-1(2H)-pyrimidinyl)methyl)-N,N-dimethylaniline NSC 136476 GANT 61

Description	GANT 61 is an inhibitor of Gli1 and Gli2 targeting the Hedgehog/GLI pathway.
Related Catalog	Signaling Pathways >> Autophagy >> Autophagy Signaling Pathways >> Stem Cell/Wnt >> Gli Research Areas >> Cancer
Target	Gli1/2[1]
In Vitro	GANT61 (20 μM) induces greater cell death than targeting Smo (cyclopamine). GANT61 (0, 5, 10, 20 μM) inhibits clonogenic survival of human colon carcinoma cell lines. GANT61 (20 μM, 0-72 hr) down-regulates Gli1 and Gli2 expression in HT29 cells. GANT61 (0, 10 μM or 20 μM) differentially regulates genes involved in the balance between cell death and cell survival[1]. GANT-61 inhibits cell viability and induces apoptosis in pancreatic CSCs. GANT-61 inhibits expression of downstream targets of Shh pathway, decreases Gli-DNA interaction, Gli transcriptional activity and Gli nuclear translocation in pancreatic CSCs. GANT-61 differentially regulates genes involved in cell survival, cell death and pluripotency. GANT-61 inhibits motility, invasion and migration of CSCs[2]. GANT61 sensitivity positively correlates to GLI1 and negatively to MYCN expression in the neuroblastoma cell lines tested. GANT61 downregulates GLI1, c-MYC, MYCN and Cyclin D1 expression and induces apoptosis of neuroblastoma cells[3].
In Vivo	GANT-61 (40 mg/kg, i.p., three days per week) inhibits CSC tumor growth in NOD/SCID IL2Rγ null mice[2]. GANT61 (50 mg/kg, p.o.) enhances the effects of chemotherapeutic drugs used in the treatment of neuroblastoma in an additive or synergistic manner and reduces the growth of established neuroblastoma xenografts in nude mice[3].
Cell Assay	Cells (1.5×104) are incubated with 0, 1, 5 and 10 μM of GANT-61 in 250 μL of culture medium in 96-well plate for 48 and 72 h. Cell viability is determined by the XTT assay. In brief, a freshly prepared XTT-PMS labeling mixture (50 μL) is added to the cell culture. The absorbance is measured at 450 nm with λ correction at 650 nm. The cell viability is expressed as ΔOD (OD450 − OD650). The apoptosis is determined by FACS analysis of propidium iodide (PI)-stained cells. In brief, cells are trypsinized, washed with PBS and resuspended in 200 μL PBS with 10 μL RNAase (10 mg/mL) and incubated at 37°C for 30 min. After incubation, 50 μL PI solution is added and cells are analyzed for apoptosis using a flow cytometry.
Animal Admin	Humanized NOD/SCID/IL2Rgammanull mice are used for the assay. Before CSC’s injection, mice are humanized with tail vein injection of human normal CD34+ peripheral blood stem/progenitor cells. CD34+peripheral blood stem/progenitor cells (500 cells/mouse, 50-75 μL volume) are injected through tail vein. After 3 days, human pancreatic CSCs (1×103 cells mixed with Matrigel, Becton Dickinson, Bedford, MA, in 75 μL total volume, 50:50 ratio) are injected subcutaneously into the flanks of NOD/SCID IL2Rγnull mice (4–6 weeks old). After two weeks of CSC implantation, mice (10 mice per group) are treated with GANT-61(0 and 40 mg/kg body weight) ip three times per week for 6 weeks. At the end of the experiment, mice are euthanized, and tumors are isolated for biochemical analysis.
References	[1]. Mazumdar T, et al. Hedgehog signaling drives cellular survival in human colon carcinoma cells. Cancer Res. 2011 Feb 1;71(3):1092-102 [2]. Fu J, et al. GANT-61 inhibits pancreatic cancer stem cell growth in vitro and in NOD/SCID/IL2R gamma null mice xenograft. Cancer Lett. 2013 Mar 1;330(1):22-32. [3]. Wickstrom M, et al. Targeting the hedgehog signal transduction pathway at the level of GLI inhibits neuroblastoma cell growth in vitro and in vivo. Int J Cancer. 2013 Apr 1;132(7):1516-24. [4]. Neelakantan D, et al. EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun. 2017 Jun 12;8:15773.

Density	1.1±0.1 g/cm3
Boiling Point	549.0±50.0 °C at 760 mmHg
Molecular Formula	C₂₇H₃₅N₅
Molecular Weight	429.600
Flash Point	285.8±30.1 °C
Exact Mass	429.289246
PSA	25.85000
LogP	3.53
Appearance	white to off-white
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.632
Storage condition	Store at -20°C
Water Solubility	DMSO: >2mg/mL

RIDADR	NONH for all modes of transport

500579-04-4	14928-10-0
1518486-61-7	1895075-34-9
199666-03-0	15128-03-7
155808-74-5	234113-94-1
4075-42-7	111905-55-6