Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates

Journal of Pharmacology and Experimental Therapeutics

Volumn 296, Issue 2, 2001, Pages 235-242

  Dunford, James E ^a   Thompson, Keith ^a   Coxon, Fraser P ^a   Luckman, Steven P ^a   Hahn, Frederick M ^c   Poulter, C Dale ^b   Ebetino, Frank H ^d   Rogers, Michael J ^a  

^a UNIVERSITY OF ABERDEEN   (United Kingdom)

^b UNIVERSITY OF UTAH   (United States)

^c UNIVERSITY OF HAWAII AT MANOA   (United States)

^d PROCTER AND GAMBLE PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALENDRONIC ACID; BISPHOSPHONIC ACID DERIVATIVE; GERANYLTRANSFERASE; GERANYLTRANSFERASE INHIBITOR; IBANDRONIC ACID; INCADRONIC ACID; MINODRONIC ACID; PAMIDRONIC ACID; RISEDRONIC ACID; UNCLASSIFIED DRUG; ZOLEDRONIC ACID;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; DRUG POTENCY; DRUG TARGETING; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; PRENYLATION; PRIORITY JOURNAL; RABBIT; STRUCTURE ACTIVITY RELATION;

ALKYL AND ARYL TRANSFERASES; ANIMALS; BONE RESORPTION; DIPHOSPHONATES; ENZYME INHIBITORS; GERANYLTRANSTRANSFERASE; INDICATORS AND REAGENTS; MEVALONIC ACID; NITROGEN COMPOUNDS; OSTEOCLASTS; PROTEIN CONFORMATION; PROTEIN ISOPRENYLATION; RABBITS; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0035146537     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (39)

1. Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis
2. 1-Hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphonic acid as a potent inhibitor of squalene synthase
3. Farnesol and geranylgeraniol prevent activation of caspases by aminobisphosphonates: Biochemical evidence for two distinct pharmacological classes of bisphosphonate drugs
4. Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase
5. Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro
6. Protein synthesis is required for caspase activation and induction of apoptosis by bisphosphonate drugs
7. Protein geranylgeranylation is required for osteoclast formation, function, and survival: Inhibition by bisphosphonates and GGTI-298
8. Bisphosphonate antiresorptive structure-activity relationships
9. Elucidation of a pharmacophore for the bisphosphonate mechanism of bone resorptive activity
10. Mechanisms of action of etidronate and other bisphosphonates
11. Isoprenoid biosynthesis in rat liver peroxisomes. Characterization of cis-prenyltransferase and squalene synthetase
12. Alendronate mechanism of action: Geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption and kinase activation in vitro
13. Bisphosphonates: Structure-activity relationships and therapeutic implications
14. Selective inhibition of farnesyl-protein transferase blocks ras processing in vivo
15. Preclinical pharmacology of CGP 42'446, a new, potent, heterocyclic bisphosphonate compound
16. Human isopentenyl diphosphate: Dimethylallyl diphosphate isomerase: Overproduction, purification, and characterization
17. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo
18. Ultrastructural and cytochemical studies on cell death of osteoclasts induced by bisphosphonate treatment
19. Mechanism of aminobisphosphonate action: Characterization of alendronate inhibition of the isoprenoid pathway
20. Heterocycle-containing bisphosphonates cause apoptosis and inhibit bone resorption by preventing protein prenylation: Evidence from structure-activity relationships in J774 macrophages
21. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras
22. BM 21.0955, a potent new bisphosphonate to inhibit bone resorption
23. Nitrogen-containing bisphosphonates as carbocation transition state analogs for isoprenoid biosynthesis
24. Crystallization and partial characterization of prenyltransferase from avian liver
25. Bisphosphonates act directly on the osteoclast to induce caspase cleavage of mst1 kinase during apoptosis. A link between inhibition of the mevalonate pathway and regulation of an apoptosis-promoting kinase
26. Cellular and molecular mechanisms of action of bisphosphonates
27. Structure-activity relationships of new heterocycle-containing bisphosphonates as inhibitors of bone resorption and as inhibitors of growth of Dictyostelium discoideum amoebae
28. Effect of a newly developed bisphosphonate, YH529, on osteolytic bone metastases in nude mice
29. Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure
30. Isopentenyldiphosphate delta-isomerase
31. Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat
32. Characteristics of clodronate-induced apoptosis in osteoclasts and macrophages
33. Antiresorptive dose-response relationships across three generations of bisphosphonates
34. The role of geranylgeranylation in bone resorption and its suppression by bisphosphonates in fetal bone explants in vitro: A clue to the mechanism of action of nitrogen-containing bisphosphonates
35. Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates
36. Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo
37. Binding and antiresorptive properties of heterocycle-containing bisphosphonate analogs: Structure-activity relationships
38. Modification of nuclear lamin proteins by a mevalonic acid derivative occurs in reticulocyte lysates and requires the cysteine residue of the C-terminal CXXM motif
39. Protein prenylation: Molecular mechanisms and functional consequences