A rapid and simple HPLC-UV method for the determination of inhibition characteristics of farnesyl transferase inhibitors

2006 ◽  
Vol 20 (2) ◽  
pp. 161-165 ◽  
Author(s):  
Natalie M. G. M. Appels ◽  
Kien-On Tung ◽  
Hilde Rosing ◽  
Jan H. M. Schellens ◽  
Jos H. Beijnen
Keyword(s):  
Farnesyl Transferase ◽  
Farnesyl Transferase Inhibitors

2P-0527 Farnesyl transferase inhibitors, by RAS P21 inactivation, induce stroke protection

2003 ◽  
Vol 4 (2) ◽  
pp. 155
Author(s):  
R. Patern ◽  
A. Ruocco ◽  
M.R. Santillo ◽  
R. Ser ◽  
G. Cuda ◽  
...  
Keyword(s):  
Farnesyl Transferase ◽  
Ras P21 ◽  
Farnesyl Transferase Inhibitors

scholarly journals Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

2008 ◽  
Vol 7 (1) ◽  
pp. 39 ◽  
Author(s):  
Kenneth A Field ◽  
Soratree Charoenthongtrakul ◽  
J Michael Bishop ◽  
Yosef Refaeli
Keyword(s):  
Transgenic Mice ◽  
B Cell ◽  
B Cell Lymphomas ◽  
Farnesyl Transferase ◽  
Farnesyl Transferase Inhibitors

Controlled Exploration of Structural Databases: The Case of Farnesyl Transferase Inhibitors

2009 ◽  
Vol 5 (3) ◽  
pp. 208-215 ◽  
Author(s):  
A. Tizot ◽  
G. Tucker ◽  
A. Pierre ◽  
J. Hickman ◽  
S. Goldstein
Keyword(s):  
Farnesyl Transferase ◽  
Farnesyl Transferase Inhibitors ◽  
Structural Databases

scholarly journals K-Ras prenylation as a potential anticancer target

2020 ◽  
Vol 39 (4) ◽  
pp. 1127-1141 ◽  
Author(s):  
Marcell Baranyi ◽  
László Buday ◽  
Balázs Hegedűs
Keyword(s):  
Critical Evaluation ◽  
Current Data ◽  
Proper Function ◽  
Kras Mutations ◽  
Farnesyl Transferase ◽  
Factors Affecting ◽  
Mutational Status ◽  
Farnesyl Transferase Inhibitors ◽  
Potential Strategy ◽  
Sensitivity Data

AbstractKRAS is one of the most commonly mutated oncogene and a negative predictive factor for a number of targeted therapies. Therefore, the development of targeting strategies against mutant KRAS is urgently needed. One potential strategy involves disruption of K-Ras membrane localization, which is necessary for its proper function. In this review, we summarize the current data about the importance of membrane-anchorage of K-Ras and provide a critical evaluation of this targeting paradigm focusing mainly on prenylation inhibition. Additionally, we performed a RAS mutation-specific analysis of prenylation-related drug sensitivity data from a publicly available database (https://depmap.org/repurposing/) of three classes of prenylation inhibitors: statins, N-bisphosphonates, and farnesyl-transferase inhibitors. We observed significant differences in sensitivity to N-bisphosphonates and farnesyl-transferase inhibitors depending on KRAS mutational status and tissue of origin. These observations emphasize the importance of factors affecting efficacy of prenylation inhibition, like distinct features of different KRAS mutations, tissue-specific mutational patterns, K-Ras turnover, and changes in regulation of prenylation process. Finally, we enlist the factors that might be responsible for the large discrepancy between the outcomes in preclinical and clinical studies including methodological pitfalls, the incomplete understanding of K-Ras protein turnover, and the variation of KRAS dependency in KRAS mutant tumors.

Farnesyl Transferase Inhibitors in Cancer

2007 ◽  
pp. 85-102
Author(s):  
Laura Fanucchi ◽  
Michael Fanucchi ◽  
Fadlo Khuri
Keyword(s):  
Farnesyl Transferase ◽  
Farnesyl Transferase Inhibitors

RAS and Leukemia: From Basic Mechanisms to Gene-Directed Therapy

1999 ◽  
Vol 17 (3) ◽  
pp. 1071-1071 ◽  
Author(s):  
Darrin M. Beaupre ◽  
Razelle Kurzrock
Keyword(s):  
Signaling Pathways ◽  
Posttranslational Modification ◽  
Antitumor Agents ◽  
Biologically Active ◽  
Ras Signaling ◽  
Farnesyl Transferase ◽  
Therapeutic Implications ◽  
Farnesyl Transferase Inhibitors

PURPOSE AND DESIGN: The purpose of this review is to provide an overview of the literature linking Ras signaling pathways and leukemia and to discuss the biologic and potential therapeutic implications of these observations. A search of MEDLINE from 1966 to October 1998 was performed. RESULTS: A wealth of data has been published on the role of Ras pathways in cancer. To be biologically active, Ras must move from the cytoplasm to the plasma membrane. Importantly, a posttranslational modification—addition of a farnesyl group to the Ras C-terminal cysteine—is a requisite for membrane localization of Ras. Farnesylation of Ras is catalyzed by an enzyme that is designated farnesyltranferase. Recently, several compounds have been developed that can inhibit farnesylation. Preclinical studies indicate that these molecules can suppress transformation and tumor growth in vitro and in animal models, with little toxicity to normal cells. CONCLUSION: An increasing body of data suggests that disruption of Ras signaling pathways, either directly through mutations or indirectly through other genetic aberrations, is important in the pathogenesis of a wide variety of cancers. Molecules such as farnesyl transferase inhibitors that interfere with the function of Ras may be exploitable in leukemia (as well as in solid tumors) as novel antitumor agents.

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