The angiogenesis inhibitor NM-3 is active against human NSCLC xenografts alone and in combination with docetaxel.
The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1 H-2-benzopyran-3-yl) propionic acid (NM-3) has completed phase I clinical evaluation as an orally bioavailable angiogenesis inhibitor. NM-3 directly kills both endothelial and tumor cells in vitro at low mM concentrations and is effective in the treatment of diverse human tumor xenografts in mice. The present work has assessed the activity of NM-3 against human non-small-cell lung cancer (NSCLC) cells when used alone and in combination with docetaxel. The results demonstrate that NM-3 decreases clonogenic survival of NSCLC cells at clinically achievable concentrations. The results also demonstrate that NM-3 is effective in the treatment of NSCLC (A549, NCI-H460) tumor xenografts in mice. Moreover, NM-3 potentiated the antitumor activity of docetaxel against NSCLC xenografts without increasing toxicity. Our findings indicate that NM-3 may be effective alone or in combination with docetaxel in the treatment of patients with NSCLC.
Agata
Naoki
N
ILEX Products, Inc., Boston, MA 02215, USA.
Nogi
Hiroko
H
Bamberg
Michael
M
Milhollen
Michael
M
Pu
Minying
M
Weitman
Steven
S
Kharbanda
Surender
S
Kufe
Donald
D
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D049934:Isocoumarins / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D049934:Isocoumarins; D043823:Taxoids; C453300:isocoumarin NM-3; D000077143:Docetaxel