BO-264
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MedKoo CAT#: 408094

CAS#: 2408648-20-2

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.

Chemical Structure

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BO-264
CAS# 2408648-20-2
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 408094
Name: BO-264
CAS#: 2408648-20-2
Chemical Formula: C18H19N5O3
Exact Mass: 353.15
Molecular Weight: 353.382
Elemental Analysis: C, 61.18; H, 5.42; N, 19.82; O, 13.58

Price and Availability

Size Price Availability Quantity
5mg USD 125 Ready to ship
10mg USD 200 Ready to ship
25mg USD 450 Ready to ship
50mg USD 750 Ready to ship
100mg USD 1250 Ready to ship
200mg USD 2250 Ready to ship
Bulk inquiry

Synonym: BO-264; BO 264; BO264;

IUPAC/Chemical Name: 3-(4-methoxyphenyl)-N-(2-morpholinopyrimidin-4-yl)isoxazol-5-amine

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)

SMILES Code: COC1=CC=C(C2=NOC(NC3=NC(N4CCOCC4)=NC=C3)=C2)C=C1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: 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.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: TACC3, a TACC family member, is frequently upregulated in a broad spectrum of cancers, including breast cancer. It plays critical roles in protecting microtubule stability and centrosome integrity that is often dysregulated in cancers; therefore, making TACC3 a highly attractive therapeutic target. BO-264 significantly decreased centrosomal TACC3 during both mitosis and interphase. BO-264 displayed potent anti-proliferative activity (~90% have less than 1 μM GI50 value) in the NCI-60 cell line panel compromising 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.

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.
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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 60.0 169.79

Preparing Stock Solutions

The following data is based on the product molecular weight 353.38 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Akbulut O, Lengerli D, Saatci O, Duman E, Seker UOS, Isik A, Akyol A, Caliskan B, Banoglu E, Sahin O. A Highly Potent TACC3 Inhibitor as a Novel Anticancer Drug Candidate. Mol Cancer Ther. 2020 Jun;19(6):1243-1254. doi: 10.1158/15357163.MCT-19-0957. Epub 2020 Mar 26. PMID: 32217742.
In vitro protocol: 1. Akbulut O, Lengerli D, Saatci O, Duman E, Seker UOS, Isik A, Akyol A, Caliskan B, Banoglu E, Sahin O. A Highly Potent TACC3 Inhibitor as a Novel Anticancer Drug Candidate. Mol Cancer Ther. 2020 Jun;19(6):1243-1254. doi: 10.1158/15357163.MCT-19-0957. Epub 2020 Mar 26. PMID: 32217742.
In vivo protocol: 1. Akbulut O, Lengerli D, Saatci O, Duman E, Seker UOS, Isik A, Akyol A, Caliskan B, Banoglu E, Sahin O. A Highly Potent TACC3 Inhibitor as a Novel Anticancer Drug Candidate. Mol Cancer Ther. 2020 Jun;19(6):1243-1254. doi: 10.1158/15357163.MCT-19-0957. Epub 2020 Mar 26. PMID: 32217742.

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Akbulut O, Lengerli D, Saatci O, et al. A Highly Potent TACC3 Inhibitor as a Novel Anti-cancer Drug Candidate [published online ahead of print, 2020 Mar 26]. Mol Cancer Ther. 2020;molcanther.0957.2019. doi:10.1158/1535-7163.MCT-19-0957