Author: Yashiro, Mitsuru ; Negi, Shigeo ; Kawakami, Kazuki ; Mima, Toru ; Yano, Takurou ; Kobayashi, Sou ; Tanaka, Yusuke ; Tatsuta, Koichi ; Shigematsu, Takashi ; Sonou, Tomohiro ; Yamamoto, Shuto ; Nakashima, Yuri ; Ohya, Masaki

Osteocytes play an important role in the regulation of serum phosphorus by producing fibroblast growth factor 23 (FGF23). FGF23 production is stimulated by 1α,25-dihydroxyvitamin D in osteocytes. However, it is unclear whether vitamin D induces FGF23 production in osteocytes directly. Therefore, we investigated vitamin D-induced FGF23 production in osteocyte-like cells derived from MC3T3-E1 osteocyte progenitor cells. We also investigated differences in the induction of FGF23 by 1α,25-dihydroxyvitamin D and various vitamin D analogs. MC3T3-E1 cells were differentiated into osteocyte-like cells (MCT3-E1-OLCs) by treatment with various agents including β-glycerophosphate and ascorbic acid. MCT3-E1-OLCs were stimulated with 1α,25-dihydroxyvitamin D₃ and subsequent FGF23 gene expression was 2631 ± 605 times higher compared with untreated cells. The expression of FGF23 in MCT3-E1-OLCs transfected with a knockdown sequence against vitamin D receptor (VDR) was significantly decreased compared with that in cells transfected with the control vector. Therefore, the induction of FGF23 in osteocytes by vitamin D may be primarily mediated via VDR. The potential of 25(OH)vitamin D₃, paricalcitol, and maxacalcitol to induce FGF23 production was almost the same as that of 1α,25-dihydroxyvitamin D₃. However, falecalcitriol and eldecalcitol demonstrated a reduced potential to induce FGF23 compared with 1α,25-dihydroxyvitamin D₃. Our results demonstrate that FGF23 induction is different among the analogs of 1α,25-dihydroxyvitamin D₃. Therefore, an appropriate vitamin D analog should be chosen for each patient with mineral and bone disorder, considering its effect on FGF23 production.

01 Mar 2018·The Journal of Steroid Biochemistry and Molecular BiologyQ2 · BIOLOGY

Recent developments for introducing a hexafluoroisopropanol unit into the Vitamin D side chain

Q2 · BIOLOGY

Review

Author: Kittaka, Atsushi ; Sugiyama, Toru ; Uesugi, Motonari ; Kawagoe, Fumihiro

Among numerous studies on synthetic approaches to and the biological activities of vitamin D analogues, we herein focused on falecalcitriol, an analogue of calcitriol (1α,25-dihydroxyvitamin D₃), in which a 26,26,26,27,27,27-hexafluoroisopropanol unit has been introduced into the side chain. Falecalcitriol was designed to escape from the metabolism of CYP24A1 and has been used as a drug to treat secondary hyperparathyroidism since 2001. Its metabolite, the 23-hydroxy form, retains biological activity and resistants to further metabolism. Recent developments in synthetic methodologies for introducing the hexafluoroisopropanol unit into the vitamin D CD-ring side chain were described herein.

01 Mar 2017·Clinical and Experimental NephrologyQ3 · MEDICINE

Research on kidney and mineral metabolism in Japan: past, present, and future

Q3 · MEDICINE

Review

Author: Ogata, Hiroaki ; Akizawa, Tadao ; Mizobuchi, Masahide ; Kinugasa, Eriko ; Koiwa, Fumihiko

Since the identification of the kidney was the main site for the synthesis of calcitriol (1α, 25-dihydroxycholecalciferol), research on chronic kidney disease (CKD)-associated mineral metabolism disorders and their management has made rapid progress. Various active analogues of calcitriol have clinically become available for treating secondary hyperparathyroidism (SHPT), which is a representative mineral metabolism abnormality in CKD patients. A calcimimetic compound cinacalcet hydrochloride has also been developed for the medical management of SHPT through a different mechanism involving the calcium-sensing receptor. The concept of CKD-mineral and bone disorder (CKD-MBD) was proposed in 2006 to provide a comprehensive understanding of a disorder related to mineral metabolism abnormalities of CKD, based on the fact that these abnormalities are closely associated with cardiovascular disease as well as bone disorders (renal osteodystrophy). There has been a recent surge in the development of phosphate binders for CKD-MBD, focused on an effort to improve mortality. In Japan, high-quality basic and clinical research on CKD-MBD has led to the development of novel therapeutic drugs, such as maxacalcitol, falecalcitriol, and bixalomer. New practice guidelines have been published and are widely adapted in clinical practice.

100 Deals associated with Falecalcitriol

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KEGG	Wiki	ATC	Drug Bank
D01662	Falecalcitriol	A11CC	-

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Hyperparathyroidism	JP	Sumitomo Pharma Co., Ltd.	04 Apr 2001
Hyperparathyroidism, Secondary	JP	Kissei Pharmaceutical Co., Ltd.	01 Apr 2001
Hypoparathyroidism	JP	Kissei Pharmaceutical Co., Ltd.	01 Apr 2001
Osteomalacia	JP	Kissei Pharmaceutical Co., Ltd.	01 Apr 2001
Rickets	JP	Kissei Pharmaceutical Co., Ltd.	01 Apr 2001

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoporosis, Postmenopausal	Phase 1	US	Windtree Therapeutics, Inc.	08 Dec 1997
Well Aging	Phase 1	US	Penederm, Inc.	05 Jun 1997
Osteoporosis, Postmenopausal	Preclinical	US	Windtree Therapeutics, Inc.	08 Dec 1997
Acne Vulgaris	Preclinical	US	Mylan Bertek Pharmaceuticals, Inc.	-
Kidney Diseases	Preclinical	JP	Taisho Pharmaceutical Co., Ltd.	-
Photodamaged skin	Preclinical	US	Mylan Bertek Pharmaceuticals, Inc.	-
Psoriasis	Preclinical	US	Mylan Bertek Pharmaceuticals, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AAIC2011	Not Applicable	Alzheimer Disease Aβ protein	32	Bapineuzumab 0.15 mg/kg	ikxasxrhzg(pejjhylyva) = jfrbbcivon tswwigtjva (tpnsbfefqp ) View more	-	01 Jul 2011
				Bapineuzumab 0.5 mg/kg	ikxasxrhzg(pejjhylyva) = xpisztmbhk tswwigtjva (tpnsbfefqp ) View more

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