Depletion of estrogen receptor in human breast tumor cells by a novel substituted indole that does not bind to the hormone binding domain.

Steroidal antiestrogens appear to have at least two major modes of action in breast cancer cells, direct antagonism of estrogen binding to its receptor and depletion of estrogen receptors (ER) due to inhibition of dimerization of the receptor and a resultant destabilization of the receptor protein. In a search for other classes of compounds which would act as dimerization inhibitors, a novel substituted indole (8-{2-[1-(4-chlorobenzoyl)-5-hydroxy-2-methyl-1H-indol-3-yl]-acetylamino} octanoic acid butyl-methyl amide, MDL 101,906) was synthesized. Binding of the ER to its consensus response element (ERE) was apparently decreased in nuclear extracts from MCF-7 human breast cancer cell treated with MDL 101,906.

An amphipathic alpha-helical decapeptide in phosphatidylcholine is an effective synthetic lung surfactant.

An idealized model amphipathic alpha-helical decapeptide was synthesized and tested for efficacy as a totally synthetic lung surfactant in simple mixtures with dipalmitoylphosphatidylcholine (DPPC). Quasi-static lung compliance was restored to 92 +/- 3% of the unlavaged value at a pressure of 5 cm H2O in an in vitro lavaged rat lung model. A sustained improvement in gas exchange was also observed when guinea pigs were treated with the synthetic lung surfactant in an in vivo lavaged lung model.