Therapeutic potential of the 2-alkyl and 2-alkylidene-19-nor-(20S)-modified analogs of 1alpha,25-dihydroxyvitamin D3.
Five analogs of 19-nor-1alpha,25-dihydroxyvitamin D(3) are described that show highly selective and potent activities. The 2-methylene-19-nor-(20S)-1alpha25-dihydroxyvitamin D(3) (2MD) and its 2alpha-methyl sister are selectively active on the osteoblast. 2MD is bone anabolic and causes bone formation in vivo and in vitro and is being developed as a therapy for bone loss diseases such as osteoporosis. 2-Methylene-19-nor (20S)-bishomo-1alpha-hydroxypregnacalciferol (2BMP) has no activity on calcium in vivo while totally suppressing circulating parathyroid hormone. Its homologs, i.e. 2-methylene-19-nor-1alpha-hydroxy-homopregnacalciferol (2MP) and 2-methylene-19-nor-1alpha-hydroxypregnacalciferol (2MPC) act similarly but are either less selective (2MP) or not as potent (2MPC). These abbreviated side chain analogs will be developed for diseases where a rise in serum calcium is not desired, as for example, cancer, renal osteodystrophy, psoriasis and autoimmune diseases.
DeLuca
Hector F
HF
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA. deluca@biochem.wisc.edu
D001842:Bone and Bones / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010024:Osteoporosis / Q000188:drug therapy
D002117:Calcitriol