Evaluation of farnesyl:protein transferase and geranylgeranyl:protein transferase inhibitor combinations in preclinical models

Cancer Research

Volumn 61, Issue 24, 2001, Pages 8758-8768

  Lobell, R B ^a   Omer, C A ^a   Abrams, M T ^a   Bhimnathwala, H G ^a   Brucker, M J ^a   Buser, C A ^a   Davide, J P ^a   DeSolms, S J ^a   Dinsmore, C J ^a   Ellis Hutchings, M S ^a   Kral, A M ^a   Liu, D ^a   Lumma, W C ^a   Machotka, S V ^a   Rands, E ^a   Williams, T M ^a   Graham, S L ^a   Hartman, G D ^a   Oliff, A I ^a   Heimbrook, D C ^a   Kohl, N E ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; GERANYLGERANYL PROTEIN TRANSFERASE INHIBITOR; PROTEIN FARNESYLTRANSFERASE INHIBITOR; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFICACY; DRUG SCREENING; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; ONCOGENE RAS; PRENYLATION; PRIORITY JOURNAL;

ALKYL AND ARYL TRANSFERASES; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; DRUG SCREENING ASSAYS, ANTITUMOR; DRUG SYNERGISM; ENZYME INHIBITORS; FARNESYLTRANSTRANSFERASE; FEMALE; HUMANS; MICE; MICE, NUDE; PANCREATIC NEOPLASMS; PROTEIN ISOPRENYLATION; RAS PROTEINS; TUMOR CELLS, CULTURED; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 0035893740     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (41)

1. Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic
2. Protein prenylation: Molecular mechanisms and functional consequences
3. Harvey murine sarcoma virus p21 ras protein: Biological and biochemical significance of the cysteine nearest the carboxy terminus
4. All ras proteins are polyisoprenylated but only some are palmitoylated
5. Famesol modification of Kirsten-ras exon 4B protein is essential for transformation
6. Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity
7. Inhibitors of protein prenylation 2000
8. Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton
9. A peptidomimetic inhibitor of farnesyl: Protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines
10. Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956
11. Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice
12. Mouse mammary tumor virus-Ki-rasB transgenic mice develop mammary carcinomas that can be growth-inhibited by a farnesyl:protein transferase inhibitor
13. Antitumor effect of a farnesyl transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice
14. Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor
15. Ras CAAX peptidomimetic FFI-277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras-Raf complexes
16. Characterization of Ha-Ras, N-Ras, Ki-Ras4a, and Ki-Ras4B as in vitro substrates for farnesyl protein transferase and geranylgeranyl protein transferase type 1
17. K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors
18. Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo
19. Specific isoprenoid modification is required for function of normal, but not oncogenic Ras function
20. Farnesyl transferase inhibitors block the famesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules
21. Pre-clinical development of farnesyltransferase inhibitors
22. Farnesyltransferase inhibitors: Antineoplastic properties, mechanisms of action, and clinical prospects
23. Farnesyltransferase and geranylgeranyltransferase I inhibitors in cancer therapy: Important mechanistic and bench to bedside issues
24. Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts
25. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: Combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine
26. Protein geranylgeranylation, not farnesylation, is required for the G1 to S phase transition in mouse fibroblasts
27. GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells
28. p21(WAF1/CIP1) is up-regulated by the geranylgeranyltransferase I inhibitor GGTI-298 through a transforming growth factor β- and Spi-responsive element: Involvement of the small GTPase RhoA
29. The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p21(WAF1/CIP1/SD11) in a p53-independent manner
30. Inhibition of the prenylation of K-Ras, but not H- or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a farnesyltransferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines
31. Combination of the novel farnesyltransferase inhibitor RPR130401 and the geranylgeranyltransferase-I inhibitor GGTI-298 disrupts MAP kinase activation and G(I)-S transition in Ki-Ras-overexpressing transformed adrenocortical cells
32. N-arylpiperazinone inhibitors of farnesyltransferase: Discovery and biological activity
33. Anions modulate the potency of geranylgeranyl-protein transferase-I inhibitors
34. Conformational restriction of flexible ligands guided by the transferred NOE experiment: Potent macrocyclic inhibitors of farnesyltransferase
35. Characterization of HDJ-2, a human 40 kD heat shock protein
36. High-performance liquid chromatography/mass spectrometry characterization of Ki4B-Ras in PSN-1 cells treated with the prenyltransferase inhibitor L-778,123
37. The farnesyl transferase inhibitor SCH 66336 induces a G2-M or G1 pause in sensitive human tumor cell lines
38. K-ras is an essential gene in the mouse with partial functional overlap with N-ras
39. Expression and regulation of endothelial nitric oxide synthase
40. Inhibition of protein geranylgeranylation causes a superinduction of nitric-oxide synthase-2 by interleukin-1β in vascular smooth muscle cells
41. Pseudopeptide inhibitors of Ras farnesyl-protein transferase