TASIN-1 (Truncated APC Selective INhibitor-1) is a nove, potent and selective small molecule inhibitor of mutant adenomatous polyposis coli (APC) with the potential to be used for CRC with mutant APC. It acts by selectively killing colorectal cancer cells that express truncated APC by reducing cellular cholesterol levels and inducing apoptotic cell death through the ER stress/ROS/JNK signaling in colon cancer cells. In two authentic human CRC cell lines HCT116 (WT APC) and DLD1 (truncated APC1417), TASIN-1 exhibited potent and selective toxicity toward DLD1 cells with IC50 value of 70 nM but not toward HCT116 cells (IC50 >50 μM). TASIN-1 also reduced the endogenous cholesterol biosynthesis rate. TASIN-1 exerted its killing effects primarily by depleting cholesterol through inhibition of emopamil-binding protein (EBP) activity. However, knockdown of truncated APC (>90%) expression desensitized DLD1 cells to TASIN-1, suggesting that APC is required for TASIN-1’s cytotoxicity.
Physicochemical Properties
| Molecular Formula | C18H28N2O3S |
| Molecular Weight | 352.491523742676 |
| Exact Mass | 352.182 |
| CAS # | 792927-06-1 |
| Related CAS # | 1678515-13-3 (HCl);792927-06-1 (free); |
| PubChem CID | 1329829 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 480.0±55.0 °C at 760 mmHg |
| Flash Point | 244.1±31.5 °C |
| Vapour Pressure | 0.0±1.2 mmHg at 25°C |
| Index of Refraction | 1.557 |
| LogP | 4.12 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 24 |
| Complexity | 481 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | XCBHYDPDIJQQGM-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H28N2O3S/c1-15-7-11-19(12-8-15)16-9-13-20(14-10-16)24(21,22)18-5-3-17(23-2)4-6-18/h3-6,15-16H,7-14H2,1-2H3 |
| Chemical Name | 1-[1-(4-methoxyphenyl)sulfonylpiperidin-4-yl]-4-methylpiperidine |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| References |
[1]. Selective targeting of mutant adenomatous polyposis coli (APC) in colorectal cancer. Sci Transl Med. 2016 Oct 19;8(361):361ra140. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~25 mg/mL (~70.92 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8370 mL | 14.1848 mL | 28.3696 mL | |
| 5 mM | 0.5674 mL | 2.8370 mL | 5.6739 mL | |
| 10 mM | 0.2837 mL | 1.4185 mL | 2.8370 mL |