ABT-751 (E 7010) 141430-65-1_Microtubule Associated_Cytoskeletal Signaling_Signaling Pathways_Products

ABT-751 (also known as ABT751; E-7010; E7010) is a novel, potent, sulfonamide-based and orally bioavailable antimitotic/antitubulin agent or tubulin inhibitor/microtubule destablizer with potential antitumor activity. It inhibits the proliferation of neuroblastoma and non-neuroblastoma cell lines with IC50 of about 1.5 and 3.4 μM, respectively. ABT-751 binds to the colchicine site on β-tubulin and inhibits polymerization of microtubules which block the G2/M phase of the cell cycle and promote apoptosis. It is not a substrate for the MDR transporter and is active against cell lines resistant to vincristine, doxorubicin, and cisplatin. In endothelial cells, ABT-751 caused significant loss of microtubules and endothelial cell retraction within 1 h in a does-dependent and reversible way.

Physicochemical Properties

Molecular Formula

C18H17N3O4S

Molecular Weight

371.41

Exact Mass

371.093

CAS #

141430-65-1

Related CAS #

141430-65-1;857447-92-8 141450-48-8 (HCl);

PubChem CID

3035714

Appearance

White to off-white solid powder

Density

1.4±0.1 g/cm3

Boiling Point

551.0±60.0 °C at 760 mmHg

Melting Point

162 °C(dec.)

Flash Point

287.0±32.9 °C

Vapour Pressure

0.0±1.5 mmHg at 25°C

Index of Refraction

1.677

LogP

4.58

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

523

Defined Atom Stereocenter Count

InChi Key

URCVCIZFVQDVPM-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H17N3O4S/c1-25-15-8-10-16(11-9-15)26(23,24)21-17-3-2-12-19-18(17)20-13-4-6-14(22)7-5-13/h2-12,21-22H,1H3,(H,19,20)

Chemical Name

N-[2-(4-hydroxyanilino)pyridin-3-yl]-4-methoxybenzenesulfonamide

Synonyms

E7010;ABT751; E 7010; ABT-751;E-7010; ABT 751

HS Tariff Code

2934.99.9001

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)

Biological Activity

ln Vitro

In vitro activity: 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.

Kinase Assay: ABT-751(E 7010) is a novel bioavailable tubulin-binding and antimitotic sulfonamide agent with IC50 of about 1.5 and 3.4 μM in neuroblastoma and non-neuroblastoma cell lines, respectively.

Cell Assay: Cells (HOS, HTB-186 Daoy, TC-71, RD, SK-N-AS, SK-N-DZ, LD and KCNR 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.

ln 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. 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 Cmax for ABT-751 at the MTD of 350 mg/m2 is 5.55 μg-hour/mL and 0.9 μg/mL, respectively.

Animal Protocol

Dissolved in 4% ethanol/96% dextrose solution (D5W) with 1 eq. 1 N HCl; 75 or 100 mg/kg; P.O.

Calu-6 NSCLC, HT-29 colon, and HCT-116 cells are injected into athymic mice.

References

Pediatr Blood Cancer.2010 Jan;54(1):47-54;Cancer Chemother Pharmacol.2007 May;59(6):725-32.

Additional Infomation

N-[2-(4-hydroxyanilino)-3-pyridinyl]-4-methoxybenzenesulfonamide is a sulfonamide.
ABT-751 has been investigated for the treatment of Lung Cancer, Non-Small Cell Lung Cancer, and Non-Small-Cell Lung Cancer.
Colchicine-Site Binding Agent ABT-751 is an orally bioavailable antimitotic sulfonamide. ABT- 751 binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of microtubules, thereby preventing tumor cell replication. This agent also disrupts tumor neovascularization, reducing tumor blood flow and so inducing a cytotoxic effect. (NCI04)

Solubility Data

Solubility (In Vitro)

DMSO: 74 mg/mL (199.2 mM)

Water:<1 mg/mL

Ethanol:12 mg/mL (32.3 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.73 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 25.0 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: ≥ 2.5 mg/mL (6.73 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 25.0 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.

Solubility in Formulation 3: 30% Propylene glycol , 5% Tween 80 , 65% D5W:15 mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6924 mL	13.4622 mL	26.9244 mL
	5 mM	0.5385 mL	2.6924 mL	5.3849 mL
	10 mM	0.2692 mL	1.3462 mL	2.6924 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.

PeptideDB

ABT-751 (E 7010) 141430-65-1

CAS No.: 141430-65-1

Physicochemical Properties

Biological Activity

Solubility Data

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PeptideDB

ABT-751 (E 7010) 141430-65-1

CAS No.: 141430-65-1

Physicochemical Properties

Biological Activity

Solubility Data

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Latest release

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