BO-264

• CAS: 2408648-20-2
• Catalog Number: ACM2408648202
• Category: Inhibitors
• Molecular Weight: 353.38
• Molecular Formula: C18H19N5O3
• Description: BO-264 is a highly potent and orally active transforming acidic coiled-coil 3 (TACC3) inhibitor with an IC50 of 188 nM and a Kd of 1.5 nM. BO-264 demonstrated superior anti-proliferative activity to the two currently reported TACC3 inhibitors, especially in aggressive breast cancer subtypes, basal and HER2+, via spindle assembly checkpoint (SAC)-dependent mitotic arrest, DNA damage and apoptosis, while the cytotoxicity against normal breast cells was negligible.
• Synonyms: BO-264; BO 264; BO264
• IUPAC Name: 3-(4-methoxyphenyl)-N-(2-morpholinopyrimidin-4-yl)isoxazol-5-amine
• Canonical SMILES: COC1=CC=C(C2=NOC(NC3=NC(N4CCOCC4)=NC=C3)=C2)C=C1
• InChI: 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)
• InChI Key: WRCGBYNVBFVRTN-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: BO-264 is a transforming acidic coiled-coil 3 (TACC3) inhibitor that blocks the function of FGFR3-TACC3 fusion protein with an IC50 of 188 nM and a Kd of 1.5 nM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 61.18; H, 5.42; N, 19.82; O, 13.58
• Exact Mass: 353.1488
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: Having validated the binding between BO-264 and the TACC3 protein, the anticancer potential of BO-264 was analyzed in comparison with the currently available TACC3 inhibitors, SPL-B (27) and KHS101 (19). To this end, its cytotoxicity was tested in several different breast cancer cell lines, as well as a normal breast cell line, MCF-12A. BO-264 inhibited the viability of basal (MDAMB-231, MDA-MB-436, CAL51, and HCC1143) and HER2+ (JIMT-1 and HCC1954) breast cancer cell lines at lower doses compared with luminal A (MCF-7, T-47D, and ZR-75-1) and luminal B (BT-474) breast cancer cell lines (Supplementary Fig. S3B). Furthermore, BO-264 IC50 with the IC50 of other two TACC3 inhibitors was compared in most sensitive cell lines and found that BO-264 had a significantly lower IC50 value (120-360 nmol/L) than SPL-B (790-3,670 nmol/L) and KHS101 (1,790-17,400 nmol/L), while no cytotoxic effect of BO-264 and other TACC3 inhibitors in the normal breast cells was observed (Fig. 3A and B). The superior anticancer activity of BO-264 has also been validated with a colony formation assay using JIMT-1 cells where a significantly lower average colony number of JIMT-1 cells was demonstrated upon treatment with BO-264 (Fig. 3C and D). These results suggest that BO-264 specifically targets breast cancer cells while sparing normal cells.; Mol Cancer Ther. 2020 Jun;19(6):1243-1254. https://mct.aacrjournals.org/content/19/6/1243.long
• In Vivo Activity: further test the antitumorigenic potential of TACC3 inhibition by BO-264 in the in vivo settings, the xenografts of HER2+ JIMT-1 cell line that is known to be highly tumorigenic, and that we demonstrated the expression of high levels of TACC3 (Supplementary Fig. S3A) was demonstrated along with the high sensitivity to BO-264 (Fig. 3A). To this end, JIMT-1 cells were injected into mammary fat pad (MFP) of female nude mice, and mice were subsequently treated with vehicle or BO-264 (25 mg/kg) for 3-4 weeks. BO-264-treated mice showed a significant suppression of tumor growth compared with vehicle-treated mice (Fig. 6A). Moreover, BO-264 was well-tolerated because treatment did not cause a significant body weight loss (Fig. 6B) and organ toxicity (Fig. 6C). A significant tumor growth inhibition and 57.1% increased lifespan in BO-264-treated mice compared with vehicle-treated ones (Fig. 6D and E) was obserbed. Inhibition of TACC3 with BO-264 leads to mitotic arrest, DNA damage, and apoptosis, similar to the results we obtained in breast cancer (Supplementary Fig. S5D) was also shown. Finally, the Mol Cancer Ther. 2020 Jun;19(6):1243-1254. https://mct.aacrjournals.org/content/19/6/1243.long antitumorigenic effect of BO-264 (50 mg/kg) was testsed on colon cancer xenografts (HCT-116) and syngeneic (CT-26) tumor models and demonstrated that BO-264 significantly impairs tumor growth (Supplementary Fig. S5E) without any significant toxicity.; Mol Cancer Ther. 2020 Jun;19(6):1243-1254. https://mct.aacrjournals.org/content/19/6/1243.long
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).