product name ABT-751 (E7010)
Description: ABT-751 (also known as E7010) is an orally bioavailable antimitotic sulfonamide. 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.
References: Pediatr Blood Cancer. 2010 Jan;54(1):47-54; Cancer Chemother Pharmacol. 2007 May;59(6):725-32.
371.41
Formula
C18H17N3O4S
CAS No.
141430-65-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 74 mg/mL (199.2 mM)
Water: <1 mg/mL
Ethanol: 12 mg/mL (32.3 mM)
Solubility (In vivo)
30% Propylene glycol, 5% Tween 80, 65% D5W: 15 mg/mL
Synonyms
E7010
other peoduct :
| In 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: 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. |
|---|---|
| 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. 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 model | Calu-6 NSCLC, HT-29 colon, and HCT-116 cells are injected into athymic mice. |
| Formulation & Dosage | Dissolved in 4% ethanol/96% dextrose solution (D5W) with 1 eq. 1 N HCl; 75 or 100 mg/kg; P.O. |
| References | Pediatr Blood Cancer. 2010 Jan;54(1):47-54; Cancer Chemother Pharmacol. 2007 May;59(6):725-32. |
