ABT-751 (E7010)

 Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

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
IC50
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 Cmax 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(Only for 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.
Solubility	30% propylene glycol, 5% Tween 80, 65% D5W, 15 mg/mL

1

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT00735878	Terminated	Non Small Cell Lung Cancer|Advanced Lung Cancer	Dartmouth-Hitchcock Medical Center|Abbott	2004-09	Phase 1|Phase 2
NCT00439296	Terminated	Recurrent Pediatric ALL|Relapsed Pediatric ALL|Acute Lymphoblastic Leukemia|Refractory Pediatric ALL	Therapeutic Advances in Childhood Leukemia Consortium	2006-05	Phase 1
NCT00297089	Completed	Lung Cancer|NSCLC|Non-Small-Cell Lung Cancer	AbbVie|AbbVie (prior sponsor, Abbott)	2006-11	Phase 1|Phase 2
NCT00436852	Completed	Disseminated Neuroblastoma|Recurrent Neuroblastoma	Children’s Oncology Group|National Cancer Institute (NCI)	2007-01	Phase 2
NCT00354562	Terminated	Lung Cancer|Non-Small Cell Lung Cancer	Abbott	2007-02	Phase 1|Phase 2

Chemical Information

Download ABT-751 (E7010) SDF

Chemical Name	N-(2-(4-hydroxyphenylamino)pyridin-3-yl)-4-methoxybenzenesulfonamide

Preparing Stock Solutions

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.37141	3.7141	7.4282	11.1423

Customer Reviews (2)

Click to enlarge	Rating
	Source	Bioorg Med Chem. 2013 Feb 15;21(4):922-31 . ABT-751 (E7010) purchased from Selleck
	Method	2D spheroid assay and 3D spheroid assay
	Cell Lines	H292 monolayer cells
	Concentrations
	Incubation Time	7 d
	Results	Cell viability in H292 monolayer cells after 3-day treatment and spheroid volume in H292 3D culture after 7-day treatment with ABT751. Data points are means ?SD for three individual experiments. IC50 values were calculated to emphasize the differences in drug potency in 2D verses 3D cultures. ABT751, IC50 of 177.2 ?17.3 nM for 2D and 670.2 ?257.6 nM for 3D.

Product Citations (1)

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  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 2012;21(4):922-31]