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Overview
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Background
SANT-1 is a novel molecule that has anti-tumour effect through its ability to bind to smoothened protein [1] .
Smoothened is one of the two types of two integral membrane proteins that regulate the activation of Hh pathway, a process that direct cellular differentiation and proliferation[1]. In addition, abnormities function of Smoothened was linked to occurrence of tumor genesis in human[1].
SANT-1 is one of the 4 Smoothened antagonists during high-throughput assay and is the molecules that have the highest antagonist effect to Smoothened protein[1]. In two healthy cell lines (Shh-LIGHT2 nM and SmoA1-LIGHT2 cell lines) , SANT-1 was able to inhibited both cells after 30 hrs of incubation with a IC50 value of 20 and 30 nM, respectively[1]. In addition, SANT-1 has the highest affinity toward Smoothened among 4 molecules, having an apparent KDs of 1.2 nM[1]. In tumor pancreas cancer cell line, SANT-1 inhibited Panc-1 cell lines with an IC50 value of 100 µM after incubation. In addition, a combination application of SANT-1 and SAHA (histone deacetylase inhibitor) enhancement the anti-tumor effectives of treatment as a result of their cooperative suppression of the Hh pathway activity[2].
No in vivo test has been carried out on SANT-1.[1]. Chen J K., Taipale J, Young K E,. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A, 2002, 99: 14071-6.
[2]. Chun SG, Zhou W & Yee N S. Combined targeting of histone deacetylases and hedgehog signaling enhances cytoxicity in pancreatic cancer. Cancer Biol Ther, 2009, 8: 1328-39.
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