ABT-751 (E7010)

Catalog No.S1165 Batch:S116501

Technical Data

Formula

C₁₈H₁₇N₃O₄S

Molecular Weight

371.41

CAS No.

141430-65-1

Solubility (25°C)*

In vitro

DMSO

74 mg/mL (199.24 mM)

Ethanol

12 mg/mL (32.3 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

30%propylene glycol 1 5%Tween80 2 65%D5W

15.0mg/ml

Taking the 1 mL working solution as an example, add 300 μL of 50 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

ABT-751 (E7010) binds to the colchicine site on β-tubulin and inhibits polymerization of microtubules, not a substrate for the MDR transporter and is active against cell lines resistant to vincristine, doxorubicin, and cisplatin. Phase 1/2.

Targets

Microtubules ^[1]

In vitro

In vitro, ABT-751 shows the selective cytotoxicity with IC50 of 0.6–2.6 μM in neuroblastoma and 0.7–4.6 μM in other solid tumor cell lines. Furthermore, ABT-751 also exhibits a selective effect on dynamic microtubules and spares stable microtubules, accounting for the persistence of acetylated and detyrosinated α-tubulin positive polymerized tubules at the IC90 concentration of ABT-751. ^[1]

In vivo

In this Calu-6 xenograft model, ABT-751 as a single agent at 100 and 75 mg/kg/day shows significant antitumor activity, while in combination with cisplatin, ABT-751 shows a dose-dependent enhancement in growth delay. In the HT-29 colon xenograft model, ABT-751 also shows significant antitumor activity as a single agent and produced a dose-dependent enhancement in growth delay In combination with 5-FU. ^[2] In dogs with lymphoma, ABT-751 exhibits the dose-limiting toxicities that included vomiting, diarrhea, anorexia, or some combination of these with a maximum tolerated dose (MTD) of 350 mg/m² PO q24h. Furthermore, the mean AUC and C_max for ABT-751 at the MTD of 350 mg/m² is 5.55 μg-hour/mL and 0.9 μg/mL, respectively. ^[3]

Features

An orally bioavailable tubulin-binding and antimitotic sulfonamide.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines HOS, HTB-186 Daoy, TC-71, RD, SK-N-AS, SK-N-DZ, LD and KCNR cells Concentrations 0 to 100 μM Incubation Time 72 hours Method Cells, in 1640 RPMI media with FBS, are plated in triplicate onto 96 well tissue culture plates in numbers determined optimal for confluent monolayer growth (5,000 cells/well for HOS, HTB-186 Daoy; 10,000 cells/well for TC-71, RD, SK-N-AS, SK-N-DZ, LD; 30,000 cells/well for KCNR), with an automated, multichannel pipette system. Cells are incubated for 24 hours at 37 °C/5% CO₂ then exposed to vehicle control (1.25% DMSO/H₂O), VCR (0.1–1000 nM), ABT-751 (0.1 nM–100 μM), and in 4 cell lines (SK-N-AS, KCNR, RD, TC-71) combretastatin (0.1–1000 nM) for 72 hours. Cells are fixed with trichloroacetic acid (final concentration 10%) at 4 °C, washed, then dried at room temperature, stained with SRB in 1% acetic acid and dye is then solubilized with Tris base. Optical density measurements are performed at 540 and 405 nm dual wavelengths in a Bio-Tek EL 340 UV plate reader.
Animal Study:^{^[2]}	Animal Models Calu-6 NSCLC, HT-29 colon, and HCT-116 cells are injected into athymic mice. Dosages 75 or 100 mg/kg/day Administration Administered via p.o.

Cell Assay:^{^[1]}

Cell lines
HOS, HTB-186 Daoy, TC-71, RD, SK-N-AS, SK-N-DZ, LD and KCNR cells
Concentrations
0 to 100 μM
Incubation Time
72 hours
Method
Cells, in 1640 RPMI media with FBS, are plated in triplicate onto 96 well tissue culture plates in numbers determined optimal for confluent monolayer growth (5,000 cells/well for HOS, HTB-186 Daoy; 10,000 cells/well for TC-71, RD, SK-N-AS, SK-N-DZ, LD; 30,000 cells/well for KCNR), with an automated, multichannel pipette system. Cells are incubated for 24 hours at 37 °C/5% CO₂ then exposed to vehicle control (1.25% DMSO/H₂O), VCR (0.1–1000 nM), ABT-751 (0.1 nM–100 μM), and in 4 cell lines (SK-N-AS, KCNR, RD, TC-71) combretastatin (0.1–1000 nM) for 72 hours. Cells are fixed with trichloroacetic acid (final concentration 10%) at 4 °C, washed, then dried at room temperature, stained with SRB in 1% acetic acid and dye is then solubilized with Tris base. Optical density measurements are performed at 540 and 405 nm dual wavelengths in a Bio-Tek EL 340 UV plate reader.

Animal Study:^{^[2]}

Animal Models
Calu-6 NSCLC, HT-29 colon, and HCT-116 cells are injected into athymic mice.
Dosages
75 or 100 mg/kg/day
Administration
Administered via p.o.

References

Customer Product Validation

: Data from [Data independently produced by Bioorg Med Chem, 2013, 21, 922-31]

: Data from [Data independently produced by Bioorg Med Chem, 2013, 21, 922-31]

: Data from [Data independently produced by , , Fitoterapia, 2017, 116:106-115]

Selleck's ABT-751 (E7010) has been cited by 5 publications

TGFβ-induced epigenetic deregulation of SOCS3 facilitates STAT3-signaling to promote fibrosis. [ J Clin Invest, 2020, 10.1172/JCI122462]	PubMed: 31990678
Curdione attenuates thrombin-induced human platelet activation: β1-tubulin as a potential therapeutic target. [Zhang D, et al. Fitoterapia, 2017, 116:106-115]	PubMed: 27915054
Gain- and Loss-of-Function Mutations in the Breast Cancer Gene GATA3 Result in Differential Drug Sensitivity [ PLoS Genet, 2016, 12(9):e1006279]	PubMed: 27588951
Bioluminescent cell-based NAD(P)/NAD(P)H assays for rapid dinucleotide measurement and inhibitor screening [ Assay Drug Dev Technol, 2014, 12(9-10):514-26]	PubMed: 25506801
Development, validation and pilot screening of an in vitro multi-cellular three-dimensional cancer spheroid assay for anti-cancer drug testing. [Rati Lama, et al. Bioorg Med Chem, 2013, 21(4):922-31]	PubMed: 23306053

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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