BO-264 is a novel and orally bioactive transforming acidic coiled-coil 3 (TACC3) inhibitor with an IC50 of 188 nM and a Kd of 1.5 nM. Through spindle assembly checkpoint (SAC)-dependent mitotic arrest, DNA damage, and apoptosis, BO-264 showed superior anti-proliferative activity compared to the two currently known TACC3 inhibitors, particularly in aggressive breast cancer subtypes, basal and HER2+. The cytotoxicity against normal breast cells was minimal.
Physicochemical Properties
| Molecular Formula | C18H19N5O3 |
| Molecular Weight | 353.375163316727 |
| Exact Mass | 353.15 |
| Elemental Analysis | C, 61.18 H, 5.42 N, 19.82 O, 13.58 |
| CAS # | 2408648-20-2 |
| Related CAS # | 2408648-20-2 |
| PubChem CID | 146018837 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 2.6 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 26 |
| Complexity | 429 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | WRCGBYNVBFVRTN-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H19N5O3/c1-24-14-4-2-13(3-5-14)15-12-17(26-22-15)20-16-6-7-19-18(21-16)23-8-10-25-11-9-23/h2-7,12H,8-11H2,1H3,(H,19,20,21) |
| Chemical Name | 3-(4-methoxyphenyl)-N-(2-morpholin-4-ylpyrimidin-4-yl)-1,2-oxazol-5-amine |
| Synonyms | BO-264; BO 264; BO264 |
| 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
| Targets | FGFR3; TACC3 (Kd = 1.5 nM); TACC3 (IC50 = 188 nM) |
| ln Vitro | BO-264 substantially reduces centrosomal TACC3 in interphase and mitosis. In the NCI-60 cell line panel, which compromises nine distinct cancer types, BO-264 exhibits strong anti-proliferative activity. BO-264 is a powerful growth inhibitor of cells expressing the FGFR3-TACC3 fusion, an oncogenic driver found in a variety of cancers.[1] |
| ln Vivo | BO-264 (25 mg/kg; oral administration; daily; for 3-4 weeks; female nude mice) treatment shows a significant suppression of tumor growth. Since BO-264 does not result in organ toxicity or a considerable reduction in body weight, it is well tolerated. |
| Cell Assay | Briefly, BO-264 (1 μM) or vehicle is incubated for 6 hours with JIMT-1 cells. Protease and phosphatase inhibitors are added to Tris-buffered saline (TBS) buffer, which is used to resuscitate cell pellets following treatment. Six PCR tubes containing the cell suspension are filled, and the temperature is raised to 45, 46, 47, 48, 49, and 50 °C for five minutes. Three consecutive cycles of freeze-thaw with liquid nitrogen are then used to lyse the cells. Western blot analysis and SDS-PAGE are used to analyze soluble proteins after they are collected by centrifugation at 20,000 g for 20 minutes at 4 °C. |
| Animal Protocol |
female nude mice with xenografts of HER2-positive JIMT-1 cell line 25 mg/kg Oral gavage |
| References |
[1]. A Highly Potent TACC3 Inhibitor as a Novel Anti-cancer Drug Candidate. Mol Cancer Ther. 2020 Mar 26. pii: molcanther.0957.2019. |
Solubility Data
| Solubility (In Vitro) | DMSO: 50~71 mg/mL (141.5~200.9 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.89 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 (5.89 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 20.8 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 3: ≥ 2.08 mg/mL (5.89 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 | 2.8298 mL | 14.1491 mL | 28.2981 mL | |
| 5 mM | 0.5660 mL | 2.8298 mL | 5.6596 mL | |
| 10 mM | 0.2830 mL | 1.4149 mL | 2.8298 mL |