Yoshiyuki Ono

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1alpha,25-Dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71), an analog of active vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2beta-position of the A-ring, it is recognized that the(More)
  • Yoshiyuki Ono
  • The Journal of steroid biochemistry and molecular…
  • 2014
Eldecalcitol (1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3, [developing code: ED-71]), a new osteoporosis treatment drug that was recently approved in Japan, is a best-in-class drug in the class of calcitriol (1α,25-dihydroxyvitamin D3) and its prodrug alfacalcidol (1α-hydroxyvitamin D3), which have been used to treat osteoporosis for 30 years. In a(More)
Eldecalcitol [1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3, developing code: ED-71] is an analog of active vitamin D3, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] that possesses a hydroxypropoxy substituent at the 2beta-position of 1,25(OH)2D3. Eldecalcitol has potent biological effects on bone and is now in preparation for approval as a promising(More)
The discovery and structure-activity relationship of a novel series of coumarin-based TNF-alpha inhibitors is described. Starting from the initial lead 1a, various derivatives were prepared surrounding the coumarin core structure to optimize the in vitro inhibitory activity of TNF-alpha production by human peripheral blood mononuclear cells (hPBMC),(More)
Eldecalcitol shows higher binding affinity for vitamin D-binding protein (DBP), tighter binding to vitamin D receptor (VDR), and resistance to metabolic degradation via 24-hydroxylation. In silico analysis of the mode of binding demonstrated that the 3-hydroxypropyloxy (3-HP) group of eldecalcitol offers additional hydrogen bond and CH-π interaction for the(More)
Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. Compound 1 was discovered from focused screening of serine protease-directed compounds from our internal collection. Using parallel synthesis supported by structure-based drug design, we identified peptidemimetic(More)
The crystal structure of human factor VIIa/soluble tissue factor (FVIIa/sTF) in complex with a highly selective peptide-mimetic FVIIa inhibitor which shows 1670-fold selectivity against thrombin inhibition has been solved at 2.6 A resolution. The inhibitor is bound to FVIIa/sTF at the S1, S2 and S3 sites and at the additional S1 subsite. Two charged groups,(More)
Anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is considered a promising therapeutic target for human cancers. We identified novel tetracyclic derivatives as potent ALK inhibitors. Among them, compound 27 showed strong cytotoxicity against KARPAS-299 with an IC(50) value of 21 nM and significant antitumor efficacy in ALK fusion-positive blood and(More)
From our research of nonsecosteroidal vitamin D(3) derivatives with gamma hydroxy carboxylic acid, we identified compound 6, with two CF(3) groups in the side chain, as a most potent vitamin D receptor (VDR) agonist that shows superagonistic activity in VDRE reporter gene assay, MG-63 osteocalcin production assay and HL-60 cell differentiation assay.(More)