Mechanisms for the selective action of Vitamin D analogs.
The non-classical effects of 1,25(OH)(2)D(3) create possible therapeutic applications for immune modulation (e.g. auto-immune diseases and graft rejection), inhibition of cell proliferation (e.g. psoriasis, cancer) and induction of cell differentiation (e.g. cancer). The major drawback related to the use of 1,25(OH)(2)D(3) is its calcemic effect, which prevents the application of pharmacological concentrations. Several analogs are now available that show modest to good selectivity with regard to specific effects (e.g. anticancer or immune effects or bone anabolism versus hypercalcemia) when tested in appropriate in vivo models. The molecular basis for this selectivity is only partially understood and probably a variable mixture of mechanisms.
Bouillon
Roger
R
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Onderwijs en Navorsing, 9th floor, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. roger.bouillon@med.kuleuven.be
Verlinden
Lieve
L
Eelen
Guy
G
De Clercq
Pierre
P
Vandewalle
Maurits
M
Mathieu
Chantal
C
Verstuyf
Annemieke
A
D000818:Animals; D004703:Endocrine System / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018167:Receptors, Calcitriol / Q000378:metabolism; D013379:Substrate Specificity; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D018167:Receptors, Calcitriol; D014807:Vitamin D