FT113 is a potent and orally bioavailable fatty acid synthase (FASN) inhibitor, with an IC50 of 213 nM for full-length recombinant human FASN enzyme. In cell-based assay, FT113 blocks FASN activity in BT474 cells (IC50, 90 nM). FT113 shows anti-proliferative activity, and exhibits anti-cancer activity both in vitro and in vivo.
Physicochemical Properties
| Molecular Formula | C22H20FN3O4 |
| Molecular Weight | 409.410308837891 |
| Exact Mass | 409.143 |
| CAS # | 1630808-89-7 |
| PubChem CID | 118621601 |
| Appearance | White to off-white solid powder |
| LogP | 1.9 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 30 |
| Complexity | 671 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC1C=CC2=C(C=1)OC(C1C=CC(=CC=1)C(N1CCN(CC1)C(C1(CC1)O)=O)=O)=N2 |
| InChi Key | DSTWHRGOCUOKDE-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H20FN3O4/c23-16-5-6-17-18(13-16)30-19(24-17)14-1-3-15(4-2-14)20(27)25-9-11-26(12-10-25)21(28)22(29)7-8-22/h1-6,13,29H,7-12H2 |
| Chemical Name | [4-(6-fluoro-1,3-benzoxazol-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone |
| 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
| ln Vitro | FT113 exhibits anti-proliferative activity with IC50 values of 47 and 26 nM, respectively, against PC3 and MV-411 cells [1]. |
| ln Vivo | In mice and simulators, the oral bioavailability of FT113 (5 mg/kg, mouse) is 95% and 84%, respectively [1]. In mice, FT113 (5, 25, or 50 mg/kg, po, twice daily for 16 days) increases the concentration of malonyl-CoA in tumors and dose-couples tumor growth inhibition [1]. |
| Animal Protocol |
Animal/Disease Models: Athymic nude mice bearing MV-411 cells [1] Doses: 5, 25, or 50 mg/kg Route of Administration: Orally, twice (two times) daily for 16 days Experimental Results: In mice, 25 mg/kg and 50 mg/kg inhibited tumor growth by 32% and 50%, respectively. |
| References |
[1]. Discovery and optimization of novel piperazines as potent inhibitors of fatty acid synthase (FASN). Bioorg Med Chem Lett. 2019 Apr 15;29(8):1001-1006. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~62.5 mg/mL (~152.66 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.08 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 20.8 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 | 2.4425 mL | 12.2127 mL | 24.4254 mL | |
| 5 mM | 0.4885 mL | 2.4425 mL | 4.8851 mL | |
| 10 mM | 0.2443 mL | 1.2213 mL | 2.4425 mL |