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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells.

Neurotensin (NT) is an autocrine growth factor for some small cell lung cancer (SCLC) cells. In this communication, the effects of a non-peptide NT receptor antagonist, SR48692, were investigated using SCLC cells. (3)H-SR48692 bound with high affinity (IC(50) = 20 nM) to NCI-H209 cells. Also, NT and SR48692 inhibited specific (125)I-NT binding with high affinity (IC(50) values of 2 and 200 nM). In contrast, the NT(2) receptor agonist, levocabastine, had little effect on specific (125)I-NT binding, second messenger production and proliferation using NCI-H209 cells. SR48692 (5 microM) antagonized the ability of NT (10 nM) to cause elevated cytosolic Ca2+ in Fura-2 AM loaded NCI-H209 cells. SR48692 antagonized the ability of NT to cause elevation of c-fos mRNA in these cells. Using a MTT proliferation assay, SR48692 inhibited NCI-H209 and H345 proliferation in a concentration-dependent manner. Using a clonogenic assay, 1 microM SR48692, reduced NCI-H209 colony number. Also, SR48692 (0.4 mg/kg per day) inhibited NCI-H209 xenograft proliferation in nude mice. These results suggest that SR48692 is a NT(1) receptor antagonist which inhibits SCLC growth.[1]


  1. SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells. Moody, T.W., Chiles, J., Casibang, M., Moody, E., Chan, D., Davis, T.P. Peptides (2001) [Pubmed]
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