| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
FGFR3; TACC3 (Kd = 1.5 nM); TACC3 (IC50 = 188 nM)
Transforming acidic coiled-coil 3 (TACC3) - potent inhibitor (IC50 = 188 nM, Kd = 1.5 nM). |
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| 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]
In vitro studies demonstrate that BO-264 is a highly potent and orally active inhibitor of transforming acidic coiled-coil 3 (TACC3) with an IC50 of 188 nM and a Kd of 1.5 nM. The compound specifically blocks the function of the FGFR3-TACC3 fusion protein, which is a driver oncogene in certain cancers including glioblastoma, bladder cancer, and others. By inhibiting TACC3, BO-264 induces spindle checkpoint-dependent mitotic arrest, DNA damage, and apoptosis in cancer cells. The compound exhibits broad-spectrum antitumor activity across various cancer cell lines, highlighting its potential as a therapeutic agent for cancers that are dependent on TACC3 function or harbor FGFR3-TACC3 fusions. |
| 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.
In vivo studies have demonstrated that BO-264 is orally active and exhibits antitumor efficacy in various cancer models. The compound's ability to inhibit TACC3 and block FGFR3-TACC3 fusion protein function translates to tumor growth inhibition in xenograft and other animal models of cancer. By inducing spindle checkpoint-dependent mitotic arrest, DNA damage, and apoptosis, BO-264 suppresses tumor growth and has the potential to overcome resistance to conventional therapies. The compound's oral bioavailability and broad-spectrum antitumor activity make it a promising candidate for further development as a cancer therapeutic, particularly for tumors that are highly proliferative and dependent on TACC3. |
| Enzyme Assay |
TACC3 inhibition assays are performed using purified recombinant TACC3 protein or cell-based assays measuring TACC3 function. For enzymatic assays, TACC3 activity is assessed using a suitable substrate or by measuring the interaction with its binding partners. IC50 values are calculated from dose-response curves. Binding affinity (Kd) is determined using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) with purified TACC3 protein. For cellular assays, the compound's ability to inhibit TACC3 function is assessed by measuring mitotic progression, spindle formation, and centrosome integrity in treated cells.
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| 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.
Cellular assays for BO-264 typically involve culturing cancer cell lines that express TACC3 or harbor FGFR3-TACC3 fusions. Cells are treated with BO-264 at various concentrations, and cell proliferation is assessed using MTT or CCK-8 assays. Cell cycle analysis is performed by flow cytometry following propidium iodide staining. Mitotic arrest is assessed by staining for phosphorylated histone H3 (pHH3) and analyzing mitotic index. Apoptosis is evaluated using Annexin V/PI staining, caspase-3/7 activity assays, or Western blotting for apoptotic markers (cleaved PARP, cleaved caspase-3). DNA damage is assessed by γ-H2AX staining. IC50 values for anti-proliferative effects are calculated from dose-response curves. |
| Animal Protocol |
female nude mice with xenografts of HER2-positive JIMT-1 cell line
25 mg/kg Oral gavage In vivo efficacy of BO-264 is evaluated in mouse xenograft models using cancer cell lines that are dependent on TACC3 or harbor FGFR3-TACC3 fusions. Tumor-bearing mice are treated with BO-264 via oral administration, and tumor volume is monitored over time. Endpoints include tumor growth inhibition, assessment of mitotic arrest and apoptosis in tumor tissues by immunohistochemistry (pHH3, cleaved caspase-3), and evaluation of DNA damage (γ-H2AX). Pharmacokinetic studies are conducted to determine the compound's bioavailability and tissue distribution. The compound's oral activity and antitumor efficacy support its potential for further development as a cancer therapeutic. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of BO-264 have been characterized to support its use as a research tool and potential therapeutic agent. The compound is orally active, which is essential for chronic administration in cancer therapy. Key PK parameters including half-life, clearance, volume of distribution, and oral bioavailability are determined using LC-MS/MS analysis of plasma and tissue samples following administration. The compound's molecular weight of 353.38 and chemical properties influence its absorption, distribution, metabolism, and excretion (ADME) characteristics. The compound's ability to reach therapeutic concentrations in tumors is important for its antitumor efficacy.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of BO-264 is typically conducted in parallel with efficacy studies in animal models. Standard toxicology assessments include in vitro cytotoxicity assays against a panel of normal and cancer cell lines to determine the compound's selectivity index. In vivo toxicity studies in rodents include acute and repeated-dose toxicity testing, observation of clinical signs and body weight changes, and histopathological examination of major organs. As a TACC3 inhibitor that induces mitotic arrest, potential effects on rapidly dividing normal tissues such as bone marrow, intestinal epithelium, and hair follicles are carefully monitored. The compound's safety profile is established to define the therapeutic window for research and development.
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| References | |
| Additional Infomation |
BO-264 is a research tool compound and potential therapeutic agent used for studying TACC3 function and its role in cancer. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves potent and selective inhibition of TACC3, which blocks the function of the FGFR3-TACC3 fusion protein and induces spindle checkpoint-dependent mitotic arrest, DNA damage, and apoptosis in cancer cells. This compound is valuable for validating TACC3 as a therapeutic target and for investigating the biology of cancers that are dependent on TACC3 function.
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| Molecular Formula |
C18H19N5O3
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|---|---|
| Molecular Weight |
353.375163316727
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| Exact Mass |
353.15
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| Elemental Analysis |
C, 61.18 H, 5.42 N, 19.82 O, 13.58
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| CAS # |
2408648-20-2
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| Related CAS # |
2408648-20-2
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| PubChem CID |
146018837
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
429
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC=C(C=C1)C2=NOC(=C2)NC3=NC(=NC=C3)N4CCOCC4
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| InChi Key |
WRCGBYNVBFVRTN-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
3-(4-methoxyphenyl)-N-(2-morpholin-4-ylpyrimidin-4-yl)-1,2-oxazol-5-amine
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| Synonyms |
BO-264; BO 264; BO264
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 50~71 mg/mL (141.5~200.9 mM)
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| 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. View More
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. |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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