Ombrabulin HCl | AVE8062 | CAS#253426-24-3 | antineoplastic agent

MedKoo Cat#: 200380 | Name: Ombrabulin HCl

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Ombrabulin HCl

CAS#253426-24-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 200380

Name: Ombrabulin HCl

CAS#: 253426-24-3 (HCl)

Chemical Formula: C21H27ClN2O6

Exact Mass: 402.1791

Molecular Weight: 438.90

Elemental Analysis: C, 57.47; H, 6.20; Cl, 8.08; N, 6.38; O, 21.87

Price and Availability

Size	Price	Availability
5mg	USD 500.00	2 Weeks
10mg	USD 750.00	2 Weeks
25mg	USD 1,100.00	2 Weeks

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Related CAS #

253426-24-3 (HCl) 181816-48-8 (free base)

Synonym

AVE8062; AVE8062; AVE8062; AVE-8062A; AC7700; AC-7700; AC 7700; 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

More Info

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. .

Product Data

Product Data

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	Water	20.0	45.57

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 438.90 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:

1: Matsumoto K, Sunaga Y, Ecstein-Fraisse E, Fujiwara K. Phase I study of ombrabulin in combination with paclitaxel and carboplatin in Japanese patients with advanced solid tumors. Int J Gynecol Cancer. 2024 Apr 1;34(4):586-593. doi: 10.1136/ijgc-2022-003880. PMID: 37989482. 2: Cren PY, Lebellec L, Ryckewaert T, Penel N. Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials. Front Oncol. 2020 Nov 24;10:594445. doi: 10.3389/fonc.2020.594445. PMID: 33330082; PMCID: PMC7732617. 3: Nishio M, Satouchi M, Horiike A, Horio Y, Sunaga Y, Ecstein-Fraisse E, Hida T. Phase 1 study of ombrabulin in combination with docetaxel and cisplatin in Japanese patients with advanced solid tumors. Jpn J Clin Oncol. 2018 Apr 1;48(4):322-328. doi: 10.1093/jjco/hyy026. PMID: 29514256. 4: Chase DM, Chaplin DJ, Monk BJ. The development and use of vascular targeted therapy in ovarian cancer. Gynecol Oncol. 2017 May;145(2):393-406. doi: 10.1016/j.ygyno.2017.01.031. Epub 2017 Feb 24. PMID: 28238563. 5: Takahashi S, Nakano K, Yokota T, Shitara K, Muro K, Sunaga Y, Ecstein-Fraisse E, Ura T. Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors. Jpn J Clin Oncol. 2016 Nov 1;46(11):1000-1007. doi: 10.1093/jjco/hyw122. PMID: 27566973. 6: Fanale D, Bronte G, Passiglia F, Calò V, Castiglia M, Di Piazza F, Barraco N, Cangemi A, Catarella MT, Insalaco L, Listì A, Maragliano R, Massihnia D, Perez A, Toia F, Cicero G, Bazan V. Stabilizing versus destabilizing the microtubules: a double-edge sword for an effective cancer treatment option? Anal Cell Pathol (Amst). 2015;2015:690916. doi: 10.1155/2015/690916. Epub 2015 Sep 21. PMID: 26484003; PMCID: PMC4592889. 7: Blay JY, Pápai Z, Tolcher AW, Italiano A, Cupissol D, López-Pousa A, Chawla SP, Bompas E, Babovic N, Penel N, Isambert N, Staddon AP, Saâda-Bouzid E, Santoro A, Franke FA, Cohen P, Le-Guennec S, Demetri GD. Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 May;16(5):531-40. doi: 10.1016/S1470-2045(15)70102-6. Epub 2015 Apr 8. PMID: 25864104. 8: Lin KY, Kwon EJ, Lo JH, Bhatia SN. Drug-induced amplification of nanoparticle targeting to tumors. Nano Today. 2014 Oct;9(5):550-559. doi: 10.1016/j.nantod.2014.09.001. Epub 2014 Sep 23. PMID: 29731806; PMCID: PMC5935498. 9: Bahleda R, Sessa C, Del Conte G, Gianni L, Capri G, Varga A, Oprea C, Daglish B, Hospitel M, Soria JC. Phase I clinical and pharmacokinetic study of ombrabulin (AVE8062) combined with cisplatin/docetaxel or carboplatin/paclitaxel in patients with advanced solid tumors. Invest New Drugs. 2014 Dec;32(6):1188-96. doi: 10.1007/s10637-014-0119-0. Epub 2014 Jun 6. PMID: 24898305. 10: von Pawel J, Gorbounova V, Reck M, Kowalski DM, Allard A, Chadjaa M, Rey A, Bennouna J, Grossi F; DISRUPT Investigators. DISRUPT: a randomised phase 2 trial of ombrabulin (AVE8062) plus a taxane-platinum regimen as first-line therapy for metastatic non-small cell lung cancer. Lung Cancer. 2014 Aug;85(2):224-9. doi: 10.1016/j.lungcan.2014.05.013. Epub 2014 May 21. PMID: 24888230. 11: Eskens FA, Tresca P, Tosi D, Van Doorn L, Fontaine H, Van der Gaast A, Veyrat-Follet C, Oprea C, Hospitel M, Dieras V. A phase I pharmacokinetic study of the vascular disrupting agent ombrabulin (AVE8062) and docetaxel in advanced solid tumours. Br J Cancer. 2014 Apr 29;110(9):2170-7. doi: 10.1038/bjc.2014.137. Epub 2014 Apr 8. PMID: 24714750; PMCID: PMC4007230. 12: Murakami H, Kurata T, Onozawa Y, Watanabe J, Ono A, Takahashi T, Yamamoto N, Fujisaka Y, Kiyota H, Hayashi H, Tanaka K, Nakagawa K, Kuroda S. An open-label, dose-escalation, safety, and pharmacokinetics phase I study of ombrabulin, a vascular disrupting agent, administered as a 30-min intravenous infusion every 3 weeks in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):623-30. doi: 10.1007/s00280-014-2388-x. Epub 2014 Jan 30. PMID: 24477603; PMCID: PMC3931931. 13: Quatrale AE, Porcelli L, Gnoni A, Numico G, Paradiso A, Azzariti A. New vascular disrupting agents in upper gastrointestinal malignancies. Curr Med Chem. 2014;21(8):1039-49. doi: 10.2174/09298673113209990233. PMID: 23992324. 14: Sessa C, Lorusso P, Tolcher A, Farace F, Lassau N, Delmonte A, Braghetti A, Bahleda R, Cohen P, Hospitel M, Veyrat-Follet C, Soria JC. Phase I safety, pharmacokinetic and pharmacodynamic evaluation of the vascular disrupting agent ombrabulin (AVE8062) in patients with advanced solid tumors. Clin Cancer Res. 2013 Sep 1;19(17):4832-42. doi: 10.1158/1078-0432.CCR-13-0427. Epub 2013 Jul 5. PMID: 23833302. 15: 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. 16: Petrillo M, Borriello M, Fuoco G, Legge F, Iannone V, Ferrandina G. Novel VEGF-independent strategies targeting tumor vasculature: clinical aspects. Curr Pharm Des. 2012;18(19):2702-12. doi: 10.2174/138161212800626184. PMID: 22390758. 17: Spear MA, LoRusso P, Mita A, Mita M. Vascular disrupting agents (VDA) in oncology: advancing towards new therapeutic paradigms in the clinic. Curr Drug Targets. 2011 Dec;12(14):2009-15. doi: 10.2174/138945011798829366. PMID: 21777190. 18: Subbiah IM, Lenihan DJ, Tsimberidou AM. Cardiovascular toxicity profiles of vascular-disrupting agents. Oncologist. 2011;16(8):1120-30. doi: 10.1634/theoncologist.2010-0432. Epub 2011 Jul 8. PMID: 21742963; PMCID: PMC3228163. 19: Cai YC, Zou Y, Xian LJ. [Advances in the study of the anti-tumor activity of small molecule vascular disrupting agents]. Yao Xue Xue Bao. 2010 Mar;45(3):283-8. Chinese. PMID: 21351502. 20: Peronneau P, Lassau N, Leguerney I, Roche A, Cosgrove D. Contrast ultrasonography: necessity of linear data processing for the quantification of tumor vascularization. Ultraschall Med. 2010 Aug;31(4):370-8. doi: 10.1055/s-0029-1245450. Epub 2010 Jun 24. PMID: 20577941.