The Farnesyl Transferase Inhibitor (FTI) SCH66336 (lonafarnib) Inhibits Rheb Farnesylation and mTOR Signaling
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چکیده
منابع مشابه
The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane and tamoxifen anti-tumor activity.
Lonafarnib (SCH66336) is a farnesyl transferase inhibitor (FTI) that inhibits the post-translational lipid modification of H-Ras and other farnesylated proteins. K- and N-Ras are also substrates of farnesyl transferase; however, upon treatment with FTIs, they are alternatively prenylated by geranylgeranyl transferase-1. Despite the failure to abrogate prenylation of K- and N-Ras, growth of many...
متن کاملOvercoming STI571 resistance with the farnesyl transferase inhibitor SCH66336.
The development of chronic myeloid leukemia (CML) is dependent on the deregulated tyrosine kinase of the oncoprotein BCR-ABL. STI571 (imatinib mesylate), an abl tyrosine kinase inhibitor, has proven remarkably effective for the treatment of CML. However, resistance to STI571 because of enhanced expression or mutation of the BCR-ABL gene has been detected in patients. In the current study we sho...
متن کاملThe farnesyl protein transferase inhibitor SCH66336 is a potent inhibitor of MDR1 product P-glycoprotein.
P-glycoprotein (Pgp)-mediated drug efflux is a major factor contributing to the variance of absorption and distribution of many drugs, particularly cancer chemotherapeutics. Multidrug resistance (MDR) is caused largely by the efflux of therapeutics out of the tumor cell by Pgp, resulting in reduced efficacy of chemotherapy. SCH66336, a farnesyl transferase inhibitor in development for cancer th...
متن کاملApoptotic synergism between STI571 and the farnesyl transferase inhibitor SCH66336 on an imatinib-sensitive cell line.
I have read the very interesting and informative article of Hoover et al,1 which may open new avenues in treating imatinib-refractory and imatinib-sensitive chronic myeloid leukemia (CML). However, when testing the synergic potential of STI farnesyl transferase inhibitor (FTI) combination on the STI571-sensitive Baf BCR-ABL-s cell line, a deficient statistical proof is shown. In their Figure 2A...
متن کاملA Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity.
Farnesyl protein transferase (FT), an enzyme that catalyzes the first step in the posttranslational modification of ras and a number of other polypeptides, has emerged as an important target for the development of anticancer agents. SCH66336 is one of the first FT inhibitors to undergo clinical testing. We report a Phase I trial to assess the maximum tolerated dose, toxicities, and biological e...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2005
ISSN: 0021-9258
DOI: 10.1074/jbc.m503763200