BO-264

SKU: orb1219892

Description

BO-264 is a highly potent and orally active inhibitor of transforming acidic coiled-coil 3 (TACC3, IC50 of 188 nM and a Kd of 1.5 nM).BO-264 demonstrated superior antiproliferative activity to the two currently reported TACC3 inhibitors, especially in aggressive breast cancer subtypes, basal and HER2+, via spindle assembly checkpoint-dependent mitotic arrest, DNA damage, and apoptosis, while the cytotoxicity against normal breast cells was negligible. Furthermore, BO-264 significantly decreased centrosomal TACC3 during both mitosis and interphase. BO-264 displayed potent antiproliferative activity ( 90% have less than 1 μmol/L GI50 value) in the NCI-60 cell line panel compromising of nine different cancer types. Noteworthy, BO-264 significantly inhibited the growth of cells harboring FGFR3-TACC3 fusion, an oncogenic driver in diverse malignancies. Importantly, its oral administration significantly impaired tumor growth in immunocompromised and immunocompetent breast and colon cancer mouse models, and increased survival without any major toxicity. Finally, TACC3 expression has been identified as strong independent prognostic factor in breast cancer and strongly prognostic in several different cancers.

Key Properties

• CAS Number: 2408648-20-2
• MW: 353.38
• Purity: >98% (HPLC)
• Formula: C₁₈H₁₉N₅O₃
• SMILES: COC1=CC=C(C2=NOC(NC3=NC(N4CCOCC4)=NC=C3)=C2)C=C1
• Target: FGFR
• Solubility: DMSO:50 mg/mL (141.49 mM; Need ultrasonic)

Bioactivity

• In Vivo:
  BO-264 (25 mg/kg; oral administration; daily; for 3-4 weeks; female nude mice) treatment shows a significant suppression of tumor growth. BO-264 is well tolerated since treatment does not causes a significant body weight loss and organ toxicity. Animal model: Female nude mice injected with JIMT-1 cells. Dosage: 25 mg/kg. Administration: Oral administration; daily; for 3-4 weeks. Result: Showed a significant suppression of tumor growth.
• In Vitro:
  BO-264 (500 nM; 48 hours; JIMT-1 cells) treatment induces a prominent increase (from 4.1% to 45.6%) in the fraction of apoptotic cells as assessed by Annexin V/PI staining. BO-264 (500 nM; 24 hours; RT112 cells) treatment decreases ERK1/2 phosphorylation, which is a marker for activated FGFR signaling along with a strong mitotic arrest. BO-264 inhibits cell viability with IC50 values of 190 nM, 160 nM, 120 nM, 130 nM and 360 nM for JIMT-1, HCC1954, MDA-MB-231, MDA-MB-436 and CAL51, respectively. BO-264 specifically targets breast cancer cells while sparing normal cells. BO-264 treatment significantly reduces the average colony number of JIMT-1 cells. BO-264 inhibits the viability of cancer cells with FGFR3-TACC3 fusion with IC50 values of 0.3 μM and 3.66 μM for RT112 and RT4, respectively. BO-264 exhibits a remarkable anti-cancer activity against more than 90% of the NCI267 60 human cancer cell lines representing nine different subpanels with GI50 values less than 1 μM. BO-264 induces mitotic arrest (prominent induces p-Histone H3 (Ser10)), apoptosis (cleaved PARP) and DNA damage, causes aberrant spindle formation and reduces centrosomal localization of TACC3 in JIMT-1 cells. Apoptosis Analysis Cell line: JIMT-1 cells. Concentration: 500 nM. Incubation time: 48 hours. Result: Induced a prominent increase (from 4.1% to 45.6%) in the fraction of apoptotic cells as assessed by Annexin V/PI staining. Concentration: 500 nM. Incubation time: 24 hours. Result: Decreased ERK1/2 phosphorylation.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

FGFR