ZD6126

ZD6126

Identifiers
IUPAC name Phosphoric acid mono-(5-acetylamino-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl) ester
Synonyms	ANG 453; AZD 6126; N-Acetylcolchicinol dihydrogenphosphate
CAS Number	219923-05-4
PubChem (CID)	9896434
ChemSpider	8072099
UNII	GBO3S6M9W7
Chemical and physical data
Formula	C20H24NO8P
Molar mass	437.38 g/mol
3D model (Jmol)	Interactive image
SMILES CC(=O)N[C@H]1CCC2=CC(=C(C(=C2C3=C1C=C(C=C3)OP(=O)(O)O)OC)OC)OC
InChI InChI=1S/C20H24NO8P/c1-11(22)21-16-8-5-12-9-17(26-2)19(27-3)20(28-4)18(12)14-7-6-13(10-15(14)16)29-30(23,24)25/h6-7,9-10,16H,5,8H2,1-4H3,(H,21,22)(H2,23,24,25)/t16-/m0/s1 Key:UGBMEXLBFDAOGL-INIZCTEOSA-N
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ZD6126 is a vascular-targeting agent and a prodrug of N-acetylcolchinol, related to colchicine.^[1] It has shown promising results on tumors in mice.^[2]

A phase I clinical trial identified gastrointestinal and cardiac effects as limiting dosing.^[3] Two phase II clinical trials were started investigating ZD6126 in metastatic renal cell carcinoma and metastatic colorectal cancer.^[4][5]

ZD6126 was being investigated by AstraZeneca as a vascular disrupting agent (VDA). However, the trials were halted, after it became apparent that ZD6126 was too cardiotoxic at the required doses.^[6]

References

1. ZD6126, National Cancer Institute summary
2. Hisatsugu Goto, Seiji Yano, Helong Zhang, Yuka Matsumori, Hirohisa Ogawa, David C. Blakey and Saburo Sone (1 July 2002). "Activity of a New Vascular Targeting Agent, ZD6126, in Pulmonary Metastases by Human Lung Adenocarcinoma in Nude Mice". Cancer Research. 62 (13): 3711–3715. PMID 12097279.
3. LoRusso Patricia M; Gadgeel Shirish M; Wozniak Antoinette; Barge Alan J; Jones Helen K; DelProposto Zachary S; DeLuca Pamela A; Evelhoch Jeffrey L; Boerner Scott A; Wheeler Catherine (2008). "Phase I clinical evaluation of ZD6126, a novel vascular-targeting agent, in patients with solid tumors". Investigational new drugs. 26 (2): 159–67. doi:10.1007/s10637-008-9112-9. PMID 18219445.
4. astrazenecaclinicaltrials.com
5. ZD6126, National Institutes of Health summary
6. Lippert John W. III (2007). "Vascular disrupting agents". Bioorganic & Medicinal Chemistry 15 (2): 605-615.