WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200380
CAS#: 253426-24-3 (HCl)
Description: Ombrabulin is a synthetic water-soluble analogue of combretastatin A4, derived from the South African willow bush (Combretum caffrum), with potential vascular-disrupting and antineoplastic activities. Ombrabulin binds to the colchicine binding site of endothelial cell tubulin, inhibiting tubulin polymerization and inducing mitotic arrest and apoptosis in endothelial cells.
MedKoo Cat#: 200380
Name: Ombrabulin HCl
CAS#: 253426-24-3 (HCl)
Chemical Formula: C21H27ClN2O6
Exact Mass: 402.17909
Molecular Weight: 438.90188
Elemental Analysis: C, 57.47; H, 6.20; Cl, 8.08; N, 6.38; O, 21.87
Related CAS #: 253426-24-3 (HCl); 181816-48-8 (free base);
Synonym: AVE8062; AVE8062; AVE8062; AVE-8062A; AC7700; AC-7700; AC 7700; CS-39-L-Ser.HCl; Ombrabulin; Ombrabulin HCl.
IUPAC/Chemical Name: (2S)-2-amino-3-hydroxy-N-[2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl]propanamide hydrochloride.
InChi Key: UQNRTPFLTRZEIM-MRWUDIQNSA-N
InChi Code: 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/b6-5-;/t15-;/m0./s1
SMILES Code: O=C(NC1=CC(/C=C\C2=CC(OC)=C(OC)C(OC)=C2)=CC=C1OC)[C@@H](N)CO.[H]Cl
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | 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. |
| In vitro activity: | TBD |
| In vivo activity: | Ombrabulin attenuated tumor growth of HEP2 and FaDu xenografts compared to control tumors. A more pronounced tumor growth delay and tumor regression were induced when ombrabulin was added to local irradiation, cisplatin or cetuximab in FaDu tumors compared to single agent treatments. Finally, triple agent therapies combining ombrabulin, irradiation, and either cisplatin or cetuximab were more effective than double combination treatment regimens and increased tumor growth delay in both HEP2 and FaDu tumor models. Reference: Invest New Drugs. 2013 Apr;31(2):273-84. https://pubmed.ncbi.nlm.nih.gov/22810221/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| Water | 20.0 | 45.57 |
The following data is based on the product molecular weight 438.90188 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | Clémenson C, Jouannot E, Merino-Trigo A, Rubin-Carrez C, Deutsch E. The vascular disrupting agent ombrabulin (AVE8062) enhances the efficacy of standard therapies in head and neck squamous cell carcinoma xenograft models. Invest New Drugs. 2013 Apr;31(2):273-84. doi: 10.1007/s10637-012-9852-4. Epub 2012 Jul 19. PMID: 22810221. |
| In vitro protocol: | TBD |
| In vivo protocol: | Clémenson C, Jouannot E, Merino-Trigo A, Rubin-Carrez C, Deutsch E. The vascular disrupting agent ombrabulin (AVE8062) enhances the efficacy of standard therapies in head and neck squamous cell carcinoma xenograft models. Invest New Drugs. 2013 Apr;31(2):273-84. doi: 10.1007/s10637-012-9852-4. Epub 2012 Jul 19. PMID: 22810221. |
1: Delmonte A, Sessa C. AVE8062: a new combretastatin derivative vascular disrupting agent. Expert Opin Investig Drugs. 2009 Oct;18(10):1541-8. Review. PubMed PMID: 19758109.
2: Hori K, Furumoto S, Kubota K. Tumor blood flow interruption after radiotherapy strongly inhibits tumor regrowth. Cancer Sci. 2008 Jul;99(7):1485-91. Epub 2008 Apr 29. PubMed PMID: 18452559.
3: Cai SX. Small molecule vascular disrupting agents: potential new drugs for cancer treatment. Recent Pat Anticancer Drug Discov. 2007 Jan;2(1):79-101. Review. PubMed PMID: 18221055.
4: Lavisse S, Lejeune P, Rouffiac V, Elie N, Bribes E, Demers B, Vrignaud P, Bissery MC, Brulé A, Koscielny S, Péronneau P, Lassau N. Early quantitative evaluation of a tumor vasculature disruptive agent AVE8062 using dynamic contrast-enhanced ultrasonography. Invest Radiol. 2008 Feb;43(2):100-11. PubMed PMID: 18197062.
5: Kim TJ, Ravoori M, Landen CN, Kamat AA, Han LY, Lu C, Lin YG, Merritt WM, Jennings N, Spannuth WA, Langley R, Gershenson DM, Coleman RL, Kundra V, Sood AK. Antitumor and antivascular effects of AVE8062 in ovarian carcinoma. Cancer Res. 2007 Oct 1;67(19):9337-45. PubMed PMID: 17909042.
6: Lippert JW 3rd. Vascular disrupting agents. Bioorg Med Chem. 2007 Jan 15;15(2):605-15. Epub 2006 Oct 27. PubMed PMID: 17070061.
7: Hori K. Antineoplastic strategy: irreversible tumor blood flow stasis induced by the combretastatin A-4 derivative AVE8062 (AC7700). Chemotherapy. 2005 Oct;51(6):357-60. Epub 2005 Oct 14. Review. PubMed PMID: 16227690.
8: Thorpe PE. Vascular targeting agents as cancer therapeutics. Clin Cancer Res. 2004 Jan 15;10(2):415-27. Review. PubMed PMID: 14760060.
9: Hori K, Saito S. Induction of tumour blood flow stasis and necrosis: a new function for epinephrine similar to that of combretastatin A-4 derivative AVE8062 (AC7700). Br J Cancer. 2004 Jan 26;90(2):549-53. PubMed PMID: 14735207; PubMed Central PMCID: PMC2409553.
10: Hori K, Saito S. Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis. Br J Cancer. 2003 Oct 6;89(7):1334-44. PubMed PMID: 14520469; PubMed Central PMCID: PMC2394288.
Ombrabulin was granted orphan drug status by the European Medicines Agency in April 2011. Ombrabulin is a combretastatin A-4 derivative that exerts its antitumor effect by disrupting the formation of blood vessels needed for tumor growth. .
