MedKoo Cat#: 406570 | Name: GANT61
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

GANT61
GANT61
CAS#500579-04-4

Theoretical Analysis

MedKoo Cat#: 406570

Name: GANT61

CAS#: 500579-04-4

Chemical Formula: C27H35N5

Exact Mass: 429.2893

Molecular Weight: 429.60

Elemental Analysis: C, 75.49; H, 8.21; N, 16.30

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,650.00 Ready to ship
1g USD 4,150.00 Ready to ship
2g USD 6,550.00 Ready to ship
5g USD 9,950.00 2 weeks
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Related CAS #
No Data
Synonym
GANT61; GANT-61; GANT 61; NSC 136476.
IUPAC/Chemical Name
2,2'-((2-(pyridin-4-yl)dihydropyrimidine-1,3(2H,4H)-diyl)bis(methylene))bis(N,N-dimethylaniline)
InChi Key
KVQOGDQTWWCZFX-UHFFFAOYSA-N
InChi Code
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
SMILES Code
CN(C)C1=CC=CC=C1CN2C(C3=CC=NC=C3)N(CC4=CC=CC=C4N(C)C)CCC2
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
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.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
        
Biological target:
GANT 61 is an inhibitor of Gli1 and Gli2 targeting the Hedgehog/GLI pathway.
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
Solvent mg/mL mM
Solubility
Ethanol 85.0 197.86
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 429.60 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
1. Mazumdar T, Devecchio J, Agyeman A, Shi T, Houghton JA. Blocking Hedgehog survival signaling at the level of the GLI genes induces DNA damage and extensive cell death in human colon carcinoma cells. Cancer Res. 2011 Sep 1;71(17):5904-14. doi: 10.1158/0008-5472.CAN-10-4173. Epub 2011 Jul 11. PMID: 21747117; PMCID: PMC3165104. 2. Pan D, Li Y, Li Z, Wang Y, Wang P, Liang Y. Gli inhibitor GANT61 causes apoptosis in myeloid leukemia cells and acts in synergy with rapamycin. Leuk Res. 2012 Jun;36(6):742-8. doi: 10.1016/j.leukres.2012.02.012. Epub 2012 Mar 6. PMID: 22398221.
In vivo protocol:
1. Qin S, Sun D, Li X, Kong F, Yu Q, Hua H, Zheng K, Tang R. GANT61 alleviates arthritic symptoms by targeting fibroblast-like synoviocytes in CIA rats. J Orthop Sci. 2019 Mar;24(2):353-360. doi: 10.1016/j.jos.2018.09.003. Epub 2018 Sep 27. PMID: 30268354.
1: Agyeman A, Jha BK, Mazumdar T, Houghton JA. Mode and specificity of binding of the small molecule GANT61 to GLI determines inhibition of GLI-DNA binding. Oncotarget. 2014 Jun 30;5(12):4492-503. PubMed PMID: 24962990; PubMed Central PMCID: PMC4147340. 2: Matsumoto T, Tabata K, Suzuki T. The GANT61, a GLI inhibitor, induces caspase-independent apoptosis of SK-N-LO cells. Biol Pharm Bull. 2014;37(4):633-41. PubMed PMID: 24694609. 3: Pan D, Li Y, Li Z, Wang Y, Wang P, Liang Y. Gli inhibitor GANT61 causes apoptosis in myeloid leukemia cells and acts in synergy with rapamycin. Leuk Res. 2012 Jun;36(6):742-8. doi: 10.1016/j.leukres.2012.02.012. Epub 2012 Mar 6. PubMed PMID: 22398221.