| http://purl.uniprot.org/citations/17636946 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17636946 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17636946 | http://www.w3.org/2000/01/rdf-schema#comment | "High-throughput screening for inhibitors of the human metalloprotease, methionine aminopeptidase-2 (MetAP2), identified a potent class of 3-anilino-5-benzylthio-1,2,4-triazole compounds. Efficient array and interative synthesis of triazoles led to rapid SAR development around the aniline, benzylthio, and triazole moeities. Evaluation of these analogs in a human MetAP2 enzyme assay led to the identification of several inhibitors with potencies in the 50-100 picomolar range. The deleterious effects on inhibitor potency by methylation of the anilino-triazole nitrogens, as well as the X-ray crystal structure of triazole 102 bound in the active site of MetAP2, confirm the key interactions between the triazole nitrogens, the active site cobalt atoms, and the His-231 side-chain. The structure has also provided a rationale for interpreting SAR within the triazole series. Key aniline (2-isopropylphenyl) and sulfur substituents (furanylmethyl) identified in the SAR studies led to the identification of potent inhibitors (103 and 104) of endothelial cell proliferation. Triazoles 103 and 104 also exhibited dose-dependent activity in an aortic ring tissue model of angiogenesis highlighting the potential utility of MetAP2 inhibitors as anticancer agents."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.org/dc/terms/identifier | "doi:10.1021/jm061182w"xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.org/dc/terms/identifier | "doi:10.1021/jm061182w"xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Ma C."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Ma C."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Yang G."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Yang G."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Yamamoto Y."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Yamamoto Y."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Yamashita K."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Yamashita K."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Janson C.A."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Janson C.A."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Meek T.D."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Meek T.D."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Tew D.G."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Tew D.G."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Veber D.F."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Veber D.F."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Ryan M.D."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Ryan M.D."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Schulz C."xsd:string |
| http://purl.uniprot.org/citations/17636946 | http://purl.uniprot.org/core/author | "Schulz C."xsd:string |