Hepoxilin analogs, potential new therapeutics in disease.
We have chemically synthesized several stable analogs of the naturally occurring hepoxilins, 12-LO products derived from arachidonic acid, which we found to have promising actions in a variety of test systems of disease. The analogs, PBTs, afford chemical and biological stability to the hepoxilin molecule. This article reviews some of our latest observations with the PBTs in the areas of inflammation (inhibition of the bleomycin-evoked lung fibrosis in mice in vivo), platelet aggregation (antagonism of the thromboxane receptor in human platelets in vitro) and thrombosis (inhibitors in vivo), and cancer (apoptosis of the human leukemia cell line, K562 in vitro and in vivo). The demonstration that the PBTs are active in vivo suggests that they can serve as a platform for their further development as novel therapeutics in disease.
Pace-Asciak
C R
CR
Research Institute, Rm. 6018, E. McMaster Bldg, The Hospital for Sick Children, Toronto, Canada. pace@sickkids.ca
Li
X
X
Qiao
N
N
Reynaud
D
D
Demin
P
P
Abdelhaleem
M
M
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin; D001792:Blood Platelets / Q000187:drug effects; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D007942:Leukemia, Experimental / Q000188:drug therapy; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control
C454099:8-hydroxy-11,12-cyclopropyleicosa-5,9,14-trienoic acid methyl ester; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D005343:Fibrinolytic Agents; D001761:Bleomycin; C022948:10-hydroxy-11,12-epoxyeicosa-5,8,14-trienoic acid; C038243:8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid; D015126:8,11,14-Eicosatrienoic Acid