| Identification | Back Directory | [Name]
E 7010 | [CAS]
141430-65-1 | [Synonyms]
E 7010
CS-505
CS-1806
ABT-751 (E
E7010(ABT-751)
ABT-751 (E7010)
E 7010 ISO 9001：2015 REACH
ABT-751 (E7010);ABT751; ABT 751
ABT751; ABT 751; E7010; E-7010; E 7010
N-[2-(4-HYDROXYANILINO)PYRIDIN-3-YL]-4-METHOXYBENZENE-1-SULFONAMIDE
N-[2-[(4-Hydroxyphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide
N-(2-(4-hydroxyphenylamino)pyridin-3-yl)-4-methoxybenzenesulfonamide
N-[2-[(4-Hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide
BenzenesulfonaMide, N-[2-[(4-hydroxyphenyl)aMino]-3-pyridinyl]-4-Methoxy- | [EINECS(EC#)]
256-495-9 | [Molecular Formula]
C18H17N3O4S | [MDL Number]
MFCD00910291 | [MOL File]
141430-65-1.mol | [Molecular Weight]
371.41 |
| Chemical Properties | Back Directory | [Melting point ]
162 °C(dec.) | [Boiling point ]
551.0±60.0 °C(Predicted) | [density ]
1.427 | [storage temp. ]
under inert gas (nitrogen or Argon) at 2–8 °C | [solubility ]
insoluble in H2O; ≥18.55 mg/mL in DMSO; ≥25.53 mg/mL in EtOH with ultrasonic | [form ]
powder to crystal | [pka]
7.86±0.40(Predicted) | [color ]
White to Yellow to Orange |
| Hazard Information | Back Directory | [Description]
ABT-751 is a tubulin polymerization inhibitor that binds to the colchicine binding site on β-tubulin (Ki = 3.3 μM).1 It inhibits tubulin polymerization in a concentration-dependent manner and inhibits growth of 26 human tumor cell lines (IC50s = 0.06-0.08 μg/ml). ABT-751 (100 mg/kg, p.o.) induces tumor regression in NB-1382 neuroblastoma, IRS56 rhabdomyosarcoma, and KT-6 Wilms mouse xenograft models.2 It also induces tumor endothelial cell retraction and reduces tumor perfusion, but not muscle perfusion, in a 9L rat glioma subcutaneous tumor model.3 | [Uses]
ABT-751 (E7010) is a novel, highly orally bioavailable sulfonamides antimitotic compound and tubulin binder. It prevents tubulin aggregation by binding to the colchicine site on β-tubulin, leading to cell cycle arrest in G2/M phase and inducing apoptosis, thus effectively preventing cell division. ABT-751 induces autophagy by inhibiting the AKT/MTOR signaling pathway. ABT-751 showed significant inhibition against various types of cancer cells, including lung, gastric, colon, and breast cancer[1][2][3][4][5][6][7][8]. | [Definition]
ChEBI: N-[2-(4-hydroxyanilino)-3-pyridinyl]-4-methoxybenzenesulfonamide is a sulfonamide. | [in vivo]
ABT-751 (100 mg/kg/day, Oral gavage (p.o.), 5 days on, 5 days off x2, 21 days) has a significant inhibitory effect in neuroblastoma models and can induce significant reduction or regression of tumor volume in rhabdomyosarcoma and nephroblastoma models. ABT-751 has synergistic effect on Vincristine and Paclitaxel (HY-B0015)[7].
ABT-751 (100 mg/kg/day, Oral gavage (p.o.), 5 days on, 5 days off x2) has a synergistic effect on Docetaxel (HY-B0011) in prostate, NSCLC, and breast tumor xenografts in mice. Improve the inhibitory effect on tumor[8].
| Animal Model: | xenograft models of neuroblastoma, osteosarcoma, Ewing sarcoma rhabdomyosarcoma, medulloblastoma and eight kidney cancer lines (six Wilms tumors, two rhabdoid)[7] | | Dosage: | 100 mg/kg | | Administration: | Oral gavage (p.o.) | | Result: | Had obvious inhibitory effect in neuroblastoma model.
Induced significant reduction or regression of tumor volume in rhabdomyosarcoma and nephroblastoma models.
Had a synergistic effect on vincristine or Paclitaxel (HY-B0015).
|
| Animal Model: | PC-3 prostate, Calu-6 NSCLC, and breast MDA-MB-468 tumor xenografts in mice[7] | | Dosage: | 75, 100 mg/kg | | Administration: | Oral gavage (p.o.) | | Result: | 與 Docetaxel 具有協(xié)同作用，提高對腫瘤的抑制作用。 |
| [References]
[1] Huang SM et al.,Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling., Nature. 2009 Oct 1;461(7264):614-20. DOI:10.1038/nature08356
[2] Elizabeth Fox et al. A Phase I Study of ABT-751, an Orally Bioavailable Tubulin Inhibitor, Administered Daily for 21 Days Every 28 Days in Pediatric Patients with Solid Tumors Clin Cancer Res February 15, 2008 14; 1111
[3] Aggarwal C, et al. Antiangiogenic agents in the management of non-small cell lung cancer: where do we stand now and where are we headed?,Cancer Biol Ther. 2012 Mar;13(5):247-63. DOI:10.4161/cbt.19594
[4] Silver M, Rusk A, Phillips B, Beck E, Jankowski M, Philibert J, Hahn K, Hershey E, McKeegan E, Bauch J, Krivoshik A, Khanna C.,Evaluation of the oral antimitotic agent (ABT-751) in dogs with lymphoma.,J Vet Intern Med. 2012 Mar-Apr;26(2):349-54. doi: 10.1111/j.1939-1676.2012.00892.x. Epub 2012 Feb 28. DOI:10.1111/j.1939-1676.2012.00892.x
[5] Gaynon PS, Harned TM; for the Therapeutic Advances in Childhood LeukemiaLymphoma (TACL) Consortium. DOI:10.1097/MPH.0b013e3182532446
[6] Morton CL, et al. Evaluation of ABT-751 against childhood cancer models in vivo. Invest New Drugs. 2007;25(4):285-295. DOI:10.1007/s10637-007-9042-y
[7] David Frost, et al. ABT-751, an oral antimitotic, shows additive and synergistic activity with docetaxel in preclinical models. Cancer Res 1 May 2007; 67 (9_Supplement): 1426.
[8] Yoshimatsu K, et al. Mechanism of action of E7010, an orally active sulfonamide antitumor agent: inhibition of mitosis by binding to the colchicine site of tubulin. Cancer Res. 1997;57(15):3208-3213. PMID:9242451 |
|
|