ZD6126

ZD6126
Clinical data
Other names	ANG 453; AZD 6126; N-Acetylcolchicinol dihydrogenphosphate
Identifiers
	IUPAC name Phosphoric acid mono-(5-acetylamino-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl) ester;
CAS Number	219923-05-4 ;
PubChem CID	9896434;
ChemSpider	8072099 ;
UNII	GBO3S6M9W7;
CompTox Dashboard (EPA)	DTXSID20944593 ;
Chemical and physical data
Formula	C20H24NO8P
Molar mass	437.385 g·mol−1
3D model (JSmol)	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 ;
	(what is this?) (verify)

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 suspended investigating ZD6126 in metastatic renal cell carcinoma and metastatic colorectal cancer.^[4]

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.^[5]

References

^ "ZD6126". NCI Drug Dictionary. U.S. National Cancer Institute.
^ Goto H, Yano S, Zhang H, Matsumori Y, Ogawa H, Blakey DC, Sone S (July 2002). "Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice". Cancer Research. 62 (13): 3711–5. PMID 12097279.
^ LoRusso PM, Gadgeel SM, Wozniak A, Barge AJ, Jones HK, DelProposto ZS, et al. (April 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. S2CID 40419869.
^ "ZD6126". ClinicalTrialsGov. U.S. National Library of Medicine.
^ Lippert JW (January 2007). "Vascular disrupting agents". Bioorganic & Medicinal Chemistry. 15 (2): 605–15. doi:10.1016/j.bmc.2006.10.020. PMID 17070061.

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[1] "ZD6126". NCI Drug Dictionary. U.S. National Cancer Institute.

[2] Goto H, Yano S, Zhang H, Matsumori Y, Ogawa H, Blakey DC, Sone S (July 2002). "Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice". Cancer Research. 62 (13): 3711–5. PMID 12097279.

[3] LoRusso PM, Gadgeel SM, Wozniak A, Barge AJ, Jones HK, DelProposto ZS, et al. (April 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. S2CID 40419869.

[4] "ZD6126". ClinicalTrialsGov. U.S. National Library of Medicine.

[pmid17070061-5] Lippert JW (January 2007). "Vascular disrupting agents". Bioorganic & Medicinal Chemistry. 15 (2): 605–15. doi:10.1016/j.bmc.2006.10.020. PMID 17070061.

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