Abstract: The present invention is directed to steroidal or terpenoidal compounds which inhibit farnesyl-protein transferase (FPTase). The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and treatment of cancer.

Abstract: The present invention relates, in general, to a protein prenyltransferase and, in particular, to protein geranylgeranyltransferase (GGTase-I) and to a nucleic acid sequence encoding same. The invention also relates to methods of producing GGTase-I and geranylgeranyl modified polypeptides. The invention further relates to a method of screening compounds for the ability to alter GGTase-I activity.

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

Abstract: The present invention comprises low molecular weight peptidyl compounds that inhibit the farnesyl-protein transferase. Furthermore, these compounds differ from the mono- or dipeptidyl analogs previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and treatment of cancer, which compound has the structure; ##STR1## or a pharmaceutically acceptable salt or disulfide thereof and wherein the variables are as defined in the specification.

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

Abstract: The present invention comprises peptidomimetic compounds which comprise a suitably substituted aminoalkylbenzene and analine analogs, further substituted with a second phenyl ring attached via a bond, a heteroatom linker or an aliphatic linker. The instant compounds inhibit the farnesyl-protein transferase enzyme and the farnesylation of certain proteins. Furthermore, the instant farnesyl protein transferase inhibitors differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Abstract: The present invention is directed to steroidal or terpenoidal compounds which inhibit farnesyl-protein transferase (FPTase). The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and treatment of cancer.

Abstract: The present invention comprises an analog of the CA.sub.1 A.sub.2 X motif of the protein Ras that is modified by farnesylation in vivo. This CA.sub.1 A.sub.2 X analog inhibits the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, this CA.sub.1 A.sub.2 X analog differs from most compounds previously described as inhibitors of farnesyl-protein transferase in that it does not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compound of the instant invention also incorporates a cyclic amine moiety in the A.sup.1 position of the motif. Further contained in this invention are chemotherapeutic compositions containing this farnesyl transferase inhibitor and methods for its production.

Abstract: Methods and compositions for treating bladder cancer using TGF-alpha or EGF fused to PE.sub.40 or cysteine modified derivatives are taught. Also, a method of producing TGF-alpha-PE.sub.40 derivatives of enhanced potency is described.

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

Abstract: The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit farnesyl-protein transferase. Furthermore, these CAAX analogues differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid antoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Abstract: The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit the farnesylation of Ras. Furthermore, these CAAX analogues differ from those previously described as inhibitors of Ras farnesyl transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Abstract: The present invention comprises peptidomimetic compounds which comprise a suitably aniline and aminoalkylbenzene moieties. The instant compounds inhibit the farnesyl-protein transferase enzyme and the farnesylation of certain proteins. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FPTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras. Furthermore, Actinoplanes sp. ATCC 55532 and Streptomces sp. ATCC 55550 are microorganisms which are capable of producing the disclosed compounds which are classified as carboxylic acid esters. In addition a method for preparing the compounds is disclosed which includes cultivating strain ATCC 55532 or strain ATCC 55550. The strains are independently capable of producing the carboxylic acid ester compounds.

Abstract: The present invention comprises analogs of the CA.sup.1 A.sup.2 X motif of the protein Ras that is modified by farnesylation in vivo. These CA.sup.1 A.sup.2 X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA.sup.1 A.sup.2 X analogs differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compounds of the instant invention also incorporate a cyclic amine moiety in the A.sup.2 position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Abstract: The present invention comprises analogs of the CA.sup.1 A.sup.2 X motif of the protein Ras that is modified by farnesylation in vivo. These CA.sup.1 A.sup.2 X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA.sup.1 A.sup.2 X analogs differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compounds of the instant invention also incorporate a cyclic amine moiety in the A.sup.2 position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Abstract: Pseudomonas exotoxin 40 is modified by deleting or substituting one or more cysteine residues. Such a modified protein, when hybridized to TGF.alpha., exhibits altered biological activities from unmodified TGF.alpha. PE.sub.40, including decreased cell killing activity and increased receptor-binding activity.

Abstract: A buffered intravesicular pharmaceutical dosage system for delivery of TGF.alpha.PE.sub.40 ab to a human bladder for bladder cancer chemotherapy, in which a buffer system of 100 mM phosphate at an initial pH of 7.8 maintains a pH range in the bladder of 6.5 to 7.8 that is sufficient to maximize interaction of TGF.alpha.PE.sub.40 ab with the EGF receptor expressed on the surface of bladder cancer cells and to prevent aggregation of the TGF.alpha.PE.sub.40 ab while in the bladder.

Abstract: Assays which comprise oligopeptides and which are useful for determining free PSA protease activity in vitro and in vivo are described. Such oligopeptides comprise amino acid sequences that are recognized and proteolytically cleaved by free prostrate specific antigen (PSA). Also described are assays useful in identifying inhibitors of free PSA.