Novel vitamin D analogs that modulate leukemic cell growth and differentiation with little effect on either intestinal calcium absorption or bone mobilization.

摘要: Induction of terminal differentiation leukemic and preleukemic cells is a therapeutic approach to leukemia preleukemia. The 1 alpha, 25- dihydroxyvitamin D3 [1,25(OH)2D3], the hormonally active form vitamin D3, can induce inhibit proliferation cells, but concentrations required achieve these effects cause life-threatening hypercalcemia. Seven new analogs 1,25(OH)2D3 were discovered be either equivalent or more potent than as assessed by: (a) inhibition clonal HL-60, EM-2, U937, patients' myeloid cells: (b) induction HL-60 promyelocytes. Furthermore, stimulated growth normal human stem cells. most analog, 1,25-dihydroxy-16ene-23yne-vitamin was about fourfold 1,25(OH)2D3. This analog decreased expression c-myc oncogene in by 50% within ten hours exposure. Effects on calcium metabolism novel vivo intestinal absorption (ICA) bone mobilization (BCM). Each mediated markedly less (10 200-fold) ICA BCM compared with To gain insight into possible mechanism action analogs, receptor binding studies done 1,25(OH)2–16ene-23yne-D3 showed that it competed only 60% effectively for receptors present 98% effective chick In summary, we have seven D are physiologic measured variety hematopoietic assays. contrast, compounds appear potential toxic (induction hypercalcemia). These may superior number clinical situations including leukemia/preleukemia; they will provide tool dissect seco-steroids promoting cellular differentiation.