N-{2-[(4-hydroxyphenyl)amino]pyridin-3-yl}-4-methoxybenzene-1-sulfonamide

• ChemBase ID: 72550
• Molecular Formular: C18H17N3O4S
• Molecular Mass: 371.41028
• Monoisotopic Mass: 371.09397704
• SMILES: c1c(ccc(c1)S(=O)(=O)Nc1c(nccc1)Nc1ccc(cc1)O)OC
• Canonical SMILES: COc1ccc(cc1)S(=O)(=O)Nc1cccnc1Nc1ccc(cc1)O
• InChI: 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)
• InChIKey: URCVCIZFVQDVPM-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-{2-[(4-hydroxyphenyl)amino]pyridin-3-yl}-4-methoxybenzene-1-sulfonamide
• IUPAC Traditional name: N-{2-[(4-hydroxyphenyl)amino]pyridin-3-yl}-4-methoxybenzenesulfonamide
• Synonyms: ABT-751

Database IDs

• CAS Number: 141430-65-1
• PubChem SID: 162037475
• PubChem CID: 3035714

CALCULATED PROPERTIES

• Acid pKa: 7.2062955
• H Acceptors: 6
• H Donor: 3
• LogD (pH = 5.5): 2.8033442
• LogD (pH = 7.4): 2.4785495
• Log P: 2.8163855
• Molar Refractivity: 97.9771 cm^3
• Polarizability: 38.162228 Å^3
• Polar Surface Area: 100.55 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Microtubule Formation

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1165

Research Area

• Description: Cancer

Biological Activity

• Description: ABT-751 (E7010) binds to the colchicine site on ?-tubulin and inhibits polymerization of microtubules.
• 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/m^2 PO q24h. Furthermore, the mean AUC and C_max for ABT-751 at the MTD of 350 mg/m^2 is 5.55 μg-hour/mL and 0.9 μg/mL, respectively. ^[3]
• Clinical Trials: ABT-751 is currently in Phase II clinical trials in patients with Colorectal Cancer.
• Features: ABT-751 is a orally bioavailable tubulin-binding and antimitotic sulfonamide.

Protocol

• Protocol: 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
• Methods: 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.
• Protocol: Animal Study ^[2]
• Animal Models: Calu-6 NSCLC, HT-29 colon, and HCT-116 cells are injected into athymic mice.
• Formulation: ABT-751 is dissolved 4% ethanol/96% dextrose solution (D5W) with 1 eq. 1 N HCl.
• Doses: 75 or 100 mg/kg/day
• Administration: Administered via p.o.

References

• References: [1] Meany HJ, et al. Pediatr Blood Cancer. 2010, 54(1), 47-54.
• References: [2] Jorgensen TJ, et al. Cancer Chemother Pharmacol. 2007, 59(6), 725-732.
• References: [3] Silver M, et al. J Vet Intern Med. 2012, 26(2), 349-354.

REFERENCES

• Meany HJ, et al. Pediatr Blood Cancer. 2010, 54(1), 47-54.
• Jorgensen TJ, et al. Cancer Chemother Pharmacol. 2007, 59(6), 725-732.
• Silver M, et al. J Vet Intern Med. 2012, 26(2), 349-354.