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| | AVE8062A Basic information |
| Product Name: | AVE8062A | | Synonyms: | AVE8062A;AC 7700;Ombrabulin (hydrochloride);Ombrabulin (AVE8062) HCl;Ombrabulin (AVE8062) hydrochloride;Ombrabulin HCl;AC7700 (hydrochloride);AVE8062 (hydrochloride) | | CAS: | 253426-24-3 | | MF: | C21H26N2O6.ClH | | MW: | 438.9 | | EINECS: | 682-340-5 | | Product Categories: | | | Mol File: | 253426-24-3.mol |  |
| | AVE8062A Chemical Properties |
| storage temp. | 2-8°C | | solubility | DMSO: soluble; Ethanol: soluble | | form | powder | | color | white to beige | | Water Solubility | H2O: 20mg/mL, clear | | InChI | 1S/C21H26N2O6.ClH/c1-26-17-8-7-13(9-16(17)23-21(25)15(22)12-24)5-6-14-10-18(27-2)20(29-4)19(11-14)28-3;/h5-11,15,24H,12,22H2,1-4H3,(H,23,25);1H | | InChIKey | UQNRTPFLTRZEIM-UHFFFAOYSA-N | | SMILES | Cl.NC(CO)C(=O)Nc1c(ccc(c1)C=Cc2cc(c(c(c2)OC)OC)OC)OC |
| WGK Germany | WGK 3 | | RTECS | TX1404540 | | Storage Class | 11 - Combustible Solids |
| | AVE8062A Usage And Synthesis |
| Uses | Ombrabulin hydrochloride is a derivative of CA-4 phosphate, which is known to exhibit antivascular effects through selective disruption of the tubulin cytoskeleton of endothelial cells. | | General Description | Ombrabulin is a member of the combretastatin A-4 compound class and is a tubulin-depolymerising tumour vascular-disrupting compound. | | Biochem/physiol Actions | Ombrabulin is a synthetic water-soluble combretastatin analog vascular disrupting agent. Ombrabulin is a tubulin polymerization inhibitor. Ombrabulin binds to the colchicine binding site of endothelial cell tubulin, inhibiting tubulin polymerization and inducing mitotic arrest and apoptosis in endothelial cells. | | in vivo | Before performing therapy experiments, the tolerability of various doses of Ombrabulin (AVE8062) ranging from 10 to 100 mg/kg is tested given twice weekly via i.v., i.p., or s.c. routes in nude mice (n=3 per group). The i.v. and s.c. routes are not pursued further due to problems with skin or tail vein necrosis. The i.p. route is well tolerated with doses up to 100 mg/kg. Next, preliminary experiments are done to determine the lowest dose for in vivo therapeutic efficacy. Starting 7 days after tumor cell injection, nude mice (n=5 per group) bearing HeyA8 ovarian cancer cells are treated with either vehicle or Ombrabulin 10, 30, 50, and 100 mg/kg twice weekly i.p. for 3 weeks. There is 65% reduction in tumor weight in the 30 mg/kg group compared with the vehicle control group (P<0.02). The 10 mg/kg dose is not effective. The antitumor effects at doses >30 mg/kg are not significantly better; therefore, the 30 mg/kg dose is selected for subsequent therapy experiments[1]. | | References | [1] Kim TJ, et al. Antitumor and antivascular effects of AVE8062 in ovarian carcinoma. Cancer Res. 2007 Oct 1;67(19):9337-45. DOI:10.1158/0008-5472.CAN-06-4018 |
| | AVE8062A Preparation Products And Raw materials |
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