Linked Life Data

11606387

Source:http://linkedlifedata.com/resource/pubmed/id/11606387

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2001-10-18
pubmed:abstractText
BMS-214662 is a potent and selective inhibitor of farnesyltransferase (FTI). In rodent fibroblasts transformed by oncogenes, BMS-214662 reversed the H-Ras-transformed phenotype but not that of K-Ras or other oncogenes. In soft agar growth assays, BMS-214662 showed good potency in inhibiting H-ras-transformed rodent cells, A2780 human ovarian carcinoma tumor cells, and HCT-116 human colon carcinoma tumor cells. Inhibition of H-Ras processing in HCT-116 human colon tumor cells was more rapid than in H-Ras-transformed rodent fibroblast tumors. BMS-214662 is the most potent apoptotic FTI known and demonstrated broad spectrum yet robust cell-selective cytotoxic activity against a panel of cell lines with diverse histology. The presence of a mutant ras oncogene was not a prerequisite for sensitivity. Athymic and conventional mice were implanted s.c. with different histological types of human and murine tumors, respectively. BMS-214662 was administered both parenterally and p.o. and was active by all these routes. Curative responses were observed in mice bearing staged human tumor xenografts including HCT-116 and HT-29 colon, MiaPaCa pancreatic, Calu-1 lung, and EJ-1 bladder carcinomas. A subline of HCT-116, HCT-116/VM46, resistant to many standard cytotoxic agents by means of a multiple drug resistance mechanism, remained quite susceptible to BMS-214662, and borderline activity was achieved against N-87 human gastric carcinoma. Two murine tumors, Lewis lung carcinoma and M5076 sarcoma, were insensitive to the FTI. In a study performed using Calu-1 tumor-bearing mice, no obvious schedule dependency of BMS-214662 was observed. The FTI, BMS-214662, demonstrated broad spectrum activity against human tumors, but murine tumors were not as sensitive.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7507-17
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11606387-Alkyl and Aryl Transferases, pubmed-meshheading:11606387-Animals, pubmed-meshheading:11606387-Antineoplastic Agents, pubmed-meshheading:11606387-Apoptosis, pubmed-meshheading:11606387-Benzodiazepines, pubmed-meshheading:11606387-Cattle, pubmed-meshheading:11606387-Drug Administration Schedule, pubmed-meshheading:11606387-Drug Screening Assays, Antitumor, pubmed-meshheading:11606387-Enzyme Inhibitors, pubmed-meshheading:11606387-Farnesyltranstransferase, pubmed-meshheading:11606387-Humans, pubmed-meshheading:11606387-Imidazoles, pubmed-meshheading:11606387-Mice, pubmed-meshheading:11606387-Mice, Inbred C57BL, pubmed-meshheading:11606387-Mice, Inbred DBA, pubmed-meshheading:11606387-Neoplasms, pubmed-meshheading:11606387-Neoplasms, Experimental, pubmed-meshheading:11606387-Xenograft Model Antitumor Assays, pubmed-meshheading:11606387-ras Proteins
pubmed:year
2001
pubmed:articleTitle
Preclinical antitumor activity of BMS-214662, a highly apoptotic and novel farnesyltransferase inhibitor.
pubmed:affiliation
Pharmaceutical Research Institute, Oncology Drug Discovery, Bristol-Myers Squibb Company, Inc., Princeton, New Jersey 08543, USA.
pubmed:publicationType
Journal Article