144848-24-8Relevant articles and documents
Synthesis and evaluation of third generation vitamin D3 analogues as inhibitors of Hedgehog signaling
Maschinot, Chad A.,Chau, Lianne Q.,Wechsler-Reya, Robert J.,Hadden, M. Kyle
, p. 495 - 506 (2019)
The Hedgehog (Hh) pathway is a developmental pathway with therapeutic potential as a target for a variety of cancers. In recent years, several vitamin D-based compounds have been identified as potent inhibitors of Hh signaling. These analogues contain aromatic phenol A-ring mimics coupled to the CD-ring side chain of vitamin D3 through modified seco-B regions. To continue structure-activity relationship studies on this class of Hh pathway inhibitors, multiple series of vitamin D-based analogues that contain an amine-based seco-B tether and/or incorporate a hydroxyl moiety on C-25 were designed and synthesized. These compounds were evaluated in multiple cell lines for their anti-Hh activity, and we identify analogues 16, 21, 22 as potent vitamin D-based Hh inhibitors (IC50 values of 110–340 nM). We also performed a series of mechanism of action studies in knockout cell lines to further explore whether these analogues inhibit the Hh pathway through a known Hh pathway component or the vitamin D receptor. While the specific cellular target that mediates these effects remains elusive, our studies suggest multiple cellular targets may mediate the anti-Hh activity of this scaffold.
Compounds, conjugates, reagent kit and application of reagent kit
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Paragraph 0056; 0062; 0063, (2018/03/01)
The invention discloses compounds, conjugates, a reagent kit for detecting vitamin D and an application of the reagent kit in detecting the vitamin D. The compounds have a structure represented by a formula (1) in the description, wherein L represents a linking arm, R1, R2 and R3 are independently selected from hydrogen, hydroxyl, C1-C3 alkoxy, C1-C3 alkyl, C2-C3 alkenyl and C2-C3 alkynyl. The compounds provided by the invention can accurately detect the vitamin D.
Synthesis of 2α-heteroarylalkyl active vitamin D3 with therapeutic effect on enhancing bone mineral density in vivo
Matsuo, Miki,Hasegawa, Asami,Takano, Masashi,Saito, Hiroshi,Kakuda, Shinji,Chida, Takayuki,Takagi, Ken-Ichiro,Ochiai, Eiji,Horie, Kyohei,Harada, Yoshifumi,Takimoto-Kamimura, Midori,Takenouchi, Kazuya,Sawada, Daisuke,Kittaka, Atsushi
supporting information, p. 671 - 674 (2013/07/26)
2α-Heteroarylethyl-1α,25-dihydroxyvitamin D3 analogues, which were designed to form a hydrogen bond between Arg274 of human vitamin D receptor (hVDR) and a nitrogen atom of the heteroaromatic ring at the 2α-position, were synthesized. Among them, 2α-[2-(tetrazol-2-yl) ethyl]-1α,25-dihydroxyvitamin D3 showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect in ovariectomized (OVX) rats, osteoporosis model animals, on enhancing bone mineral density than those of active vitamin D 3. X-ray cocrystallographic analysis of the hVDR-ligand complex confirms that the new hydrogen bond formation stabilized the complex.
