During the year the receptor pharmacology and molecular pharmacology of primarily of the bombesin receptor family (GRPR, NMBR, BRS-3) was investigated as well as publishing a a review of advances in this field. Classical bombesin receptors (GRPR,NMBR) are commonly overexpressed on lung cancer cells and effect tumor growth. We investigated the presence and effect of an orphan receptor, BRS-3 closely related to classical bombesin receptors in a number of lung cancer cell lines. Our studied demonstrated they are frequently present in these cell lines and their activation stimulates growth, primarily by transactivation of the EGF receptor. This raises the possibility that they could be an important antigrowth target in these cells. In collaboration with Dr TW Moody (NCI) and Prof Bottle, Queensland, Australia, hybrid nitroxide-based nonsteroidal anti-inflammatory drugs were designed, synthesized and evaluated for biological activity. A number of these compounds demonstrated enhanced anti-inflammatory activity over currently used compounds. In collaboration with Prof M Leopoldo of the University deli Study di Bari Aldo Moro, Bari, Italy, a number of potential small molecule inhibitors of Bombesin receptors were screened. Two were discovered to function as BnR antagonists, AM-37 and ST-36. In the micro-molar range each of these inhibited BB1, BB2 and BB3 activation and may be useful as templates to develop more potent antagonistic analogues
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