ChemInform Abstract: Rhombenone: Farnesyl Protein Transferase Inhibitor from the Leaves of Hedera rhombea Bean

ChemInform ◽  
2010 ◽  
Vol 28 (35) ◽  
pp. no-no
Author(s):  
B.-M. KWON ◽  
S.-H. LEE ◽  
K.-S. KIM ◽  
I.-R. LEE ◽  
U. C. LEE ◽  
...  
Keyword(s):  
Farnesyl Protein Transferase ◽  
Hedera Rhombea

Rhombenone: farnesyl protein transferase inhibitor from the leaves of Hedera rhombea Bean

1997 ◽  
Vol 7 (8) ◽  
pp. 971-974 ◽  
Author(s):  
Byoung-Mog Kwon ◽  
Seung-Ho Lee ◽  
Kyung-Sook Kim ◽  
Ihn-Rhan Lee ◽  
Un Chul Lee ◽  
...  
Keyword(s):  
Farnesyl Protein Transferase ◽  
Hedera Rhombea

scholarly journals Selective inhibition of farnesyl-protein transferase blocks ras processing in vivo.

1993 ◽  
Vol 268 (11) ◽  
pp. 7617-7620
Author(s):  
J.B. Gibbs ◽  
D.L. Pompliano ◽  
S.D. Mosser ◽  
E. Rands ◽  
R.B. Lingham ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Farnesyl Protein Transferase

A Simple and Efficient Route to Chaetomellic Anhydride A: A Potent Natural Ras Farnesyl-Protein Transferase Inhibitor.

ChemInform ◽  
2004 ◽  
Vol 35 (47) ◽  
Author(s):  
Laurent De Buyck ◽  
Rita Cagnoli ◽  
Franco Ghelfi ◽  
Giulia Merighi ◽  
Adele Mucci ◽  
...  
Keyword(s):  
Farnesyl Protein Transferase ◽  
Efficient Route

Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton

1994 ◽  
Vol 14 (6) ◽  
pp. 4193-4202
Author(s):  
G C Prendergast ◽  
J P Davide ◽  
S J deSolms ◽  
E A Giuliani ◽  
S L Graham ◽  
...  
Keyword(s):  
Cell Growth ◽  
Fiber Formation ◽  
Transformed Cells ◽  
Actin Stress Fiber ◽  
Actin Organization ◽  
Stress Fiber Formation ◽  
Molecule Inhibitor ◽  
Farnesyl Protein Transferase ◽  
Actin Stress Fiber Formation ◽  
Inhibitor Treatment

A potent and specific small molecule inhibitor of farnesyl-protein transferase, L-739,749, caused rapid morphological reversion and growth inhibition of ras-transformed fibroblasts (Rat1/ras cells). Morphological reversion occurred within 18 h of L-739,749 addition. The reverted phenotype was stable for several days in the absence of inhibitor before the transformed phenotype reappeared. Cell enlargement and actin stress fiber formation accompanied treatment of both Rat1/ras and normal Rat1 cells. Significantly, inhibition of Ras processing did not correlate with the initiation or maintenance of the reverted phenotype. While a single treatment with L-739,749 was sufficient to morphologically revert Rat1/ras cells, repetitive inhibitor treatment was required to significantly reduce cell growth rate. Thus, the effects of L-739,749 on transformed cell morphology and cytoskeletal actin organization could be separated from effects on cell growth, depending on whether exposure to a farnesyl-protein transferase inhibitor was transient or repetitive. In contrast, L-739,749 had no effect on the growth, morphology, or actin organization of v-raf-transformed cells. Taken together, the results suggest that the mechanism of morphological reversion is complex and may involve farnesylated proteins that control the organization of cytoskeletal actin.

Clavaric Acid and Steroidal Analogues as Ras- and FPP-Directed Inhibitors of Human Farnesyl-Protein Transferase

1998 ◽  
Vol 41 (23) ◽  
pp. 4492-4501 ◽  
Author(s):  
Russell B. Lingham ◽  
Keith C. Silverman ◽  
Hiranthi Jayasuriya ◽  
B. Moon Kim ◽  
Suzanne E. Amo ◽  
...  
Keyword(s):  
Farnesyl Protein Transferase

scholarly journals Novel Tricyclic Inhibitors of Farnesyl Protein Transferase

1995 ◽  
Vol 270 (51) ◽  
pp. 30611-30618 ◽  
Author(s):  
W. Robert Bishop ◽  
Richard Bond ◽  
Joanne Petrin ◽  
Lynn Wang ◽  
Robert Patton ◽  
...  
Keyword(s):  
Farnesyl Protein Transferase

scholarly journals Characterization of Ha-Ras, N-Ras, Ki-Ras4A, and Ki-Ras4B asin VitroSubstrates for Farnesyl Protein Transferase and Geranylgeranyl Protein Transferase Type I

1997 ◽  
Vol 272 (15) ◽  
pp. 10232-10239 ◽  
Author(s):  
Fang L. Zhang ◽  
Paul Kirschmeier ◽  
Donna Carr ◽  
Linda James ◽  
Richard W. Bond ◽  
...  
Keyword(s):  
Type I ◽  
Farnesyl Protein Transferase

Biochemical and Biological Analyses of Farnesyl-Protein Transferase Inhibitors

2003 ◽  
pp. 283-292
Author(s):  
Nancy E. Kohl ◽  
Kenneth S. Koblan ◽  
Charles A. Omer ◽  
Allen Oliff ◽  
Jackson B. Gibbs
Keyword(s):  
Farnesyl Protein Transferase

Phase I and Pharmacokinetic Study of Farnesyl Protein Transferase Inhibitor R115777 in Advanced Cancer

2000 ◽  
Vol 18 (4) ◽  
pp. 927-927 ◽  
Author(s):  
J. Zujewski ◽  
I.D. Horak ◽  
C.J. Bol ◽  
R. Woestenborghs ◽  
C. Bowden ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Performance Status ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Oral Drug ◽  
Total Daily Dose ◽  
Pharmacokinetic Data ◽  
Metastatic Colon Cancer ◽  
Phase Ii Trials ◽  
Farnesyl Protein Transferase

PURPOSE: To determine the maximum-tolerated dose, toxicities, and pharmacokinetic profile of the farnesyl protein transferase inhibitor R115777 when administered orally bid for 5 days every 2 weeks. PATIENTS AND METHODS: Twenty-seven patients with a median age of 58 years received 85 cycles of R115777 using an intrapatient and interpatient dose escalation schema. Drug was administered orally at escalating doses as a solution (25 to 850 mg bid) or as pellet capsules (500 to 1300 mg bid). Pharmacokinetics were assessed after the first dose and the last dose administered during cycle 1. RESULTS: Dose-limiting toxicity of grade 3 neuropathy was observed in one patient and grade 2 fatigue (decrease in two performance status levels) was seen in four of six patients treated with 1,300 mg bid. The most frequent clinical grade 2 or 3 adverse events in any cycle included nausea, vomiting, headache, fatigue, anemia, and hypotension. Myelosuppression was mild and infrequent. Peak plasma concentrations of R115777 were achieved within 0.5 to 4 hours after oral drug administration. The elimination of R115777 from plasma was biphasic, with sequential half-lives of about 5 hours and 16 hours. There was little drug accumulation after bid dosing, and steady-state concentrations were achieved within 2 to 3 days. The pharmacokinetics were dose proportional in the 25 to 325 mg/dose range for the oral solution. Urinary excretion of unchanged R115777 was less than 0.1% of the oral dose. One patient with metastatic colon cancer treated at the 500-mg bid dose had a 46% decrease in carcinoembryonic antigen levels, improvement in cough, and radiographically stable disease for 5 months. CONCLUSION: R115777 is bioavailable after oral administration and has an acceptable toxicity profile. Based upon pharmacokinetic data, the recommended dose for phase II trials is 500 mg orally bid (total daily dose, 1,000 mg) for 5 consecutive days followed by 9 days of rest. Studies of continuous dosing and studies of R115777 in combination with chemotherapy are ongoing.

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