SANT-1

• CAT Number: I011873
• CAS Number: 304909-07-7
• Molecular Formula: C23H27N5
• Molecular Weight: 373.504
• Purity: ≥95%
• Target: Hedgehog
• Solubility: >18.75mg/mL in DMSO
• Storage: Desiccate at +4°C
• IUPAC Name: (E)-N-(4-benzylpiperazin-1-yl)-1-(3,5-dimethyl-1-phenylpyrazol-4-yl)methanimine
• InChI: InChI=1S/C23H27N5/c1-19-23(20(2)28(25-19)22-11-7-4-8-12-22)17-24-27-15-13-26(14-16-27)18-21-9-5-3-6-10-21/h3-12,17H,13-16,18H2,1-2H3/b24-17+
• InChIKey: FOORCIAZMIWALX-JJIBRWJFSA-N
• SMILES: CC1=C(C(=NN1C2=CC=CC=C2)C)C=NN3CCN(CC3)CC4=CC=CC=C4

SANT-1 (CAT: I011873) is a potent and selective inhibitor of the Sonic hedgehog (Shh) pathway, which has shown potential as an anticancer agent. The Shh pathway plays a crucial role in various biological processes, including cell growth, differentiation, and tissue development. In certain cancers, including acute myeloid leukemia (AML), aberrant activation of the Shh pathway has been observed, contributing to drug resistance and cancer stem cell maintenance. SANT-1 inhibits the activity of the Shh pathway, thereby interfering with the signaling cascade and potentially suppressing tumor growth and drug resistance in AML and other cancers.

Reference

1. Cancer Lett. 2013 Aug 19;336(2):347-58. doi: 10.1016/j.canlet.2013.03.025. Epub
2013 Mar 31.

Guggulsterone sensitizes glioblastoma cells to Sonic hedgehog inhibitor SANT-1
induced apoptosis in a Ras/NFκB dependent manner.

Dixit D(1), Ghildiyal R, Anto NP, Ghosh S, Sharma V, Sen E.

Author information:
(1)National Brain Research Centre, Manesar, Haryana 122 050, India.

Since Shh pathway effector, Gli1, is overexpressed in gliomas, we investigated
the effect of novel Shh inhibitor SANT-1 on glioma cell viability. Though SANT-1
failed to induce apoptosis, it reduced proliferation of glioma stem-like cells.
Apart from canonical Shh cascade, Gli1 is also induced by non-canonical pathways
including NFκB. Therefore, a combinatorial strategy with Ras/NFκB inhibitor,
Guggulsterone, was employed to enhance effectiveness of SANT-1. Guggulsterone
inhibited Ras and NFκB activity and sensitized cells to SANT-1 induced apoptosis
via intrinsic apoptotic mechanism. Inhibition of either Ras or NFκB activity was
sufficient to sensitize cells to SANT-1. Guggulsterone induced ERK activation
also contributed to Caspase-9 activation. Since SANT-1 and Guggulsterone
differentially target stem-like and non-stem glioma cells respectively, this
combination warrants investigation as an effective anti-glioma therapy.

2. Biochim Biophys Acta. 2005 Feb 14;1727(2):81-6. Epub 2005 Jan 13.

The Terminal acidic SANT 1 (Tacs1) gene of maize is expressed in tissues
containing meristems and encodes an acidic SANT domain similar to some
chromatin-remodeling complex proteins.

Marian CO(1), Bass HW.

Author information:
(1)Department of Biological Science, Florida State University, Tallahassee, FL
32306-4370, USA.

While screening for plant homologs of telomeric-complex proteins, we isolated a
cDNA for the Terminal acidic SANT 1 (Tacs1) gene of maize, encoding a 45-kDa
protein with a C-terminal Myb/SANT-like domain. Gene expression and protein
modeling data indicate that the TACS1 protein may function in chromatin
remodeling within shoot primordia or other meristem-containing tissues.