Inecalcitol

Names

[ Name ]:
Inecalcitol

[Synonym ]:
(1R,3R,7E,14β,17β)-17-[(2R)-6-Hydroxy-6-methyl-4-heptyn-2-yl]-9,10-secoestra-5,7-diene-1,3-diol
1,3-Cyclohexanediol, 5-[(2E)-2-[(1R,3aR,7aR)-octahydro-1-[(1R)-5-hydroxy-1,5-dimethyl-3-hexyn-1-yl]-7a-methyl-4H-inden-4-ylidene]ethylidene]-, (1R,3R)-
UNII:05FZV98342
19-Nor-14-epi-23-yne-1,25 dihydroxyvitamin D3
TX 522
Inecalcitol
(7E)-(1R,3R,14R)-19-nor-23-yne-9,10-seco-5,7-cholestadiene-1,3,25-triol
MFCD09838524

Biological Activity

[Description]:

Inecalcitol (TX 522), a unique vitamin D3 analog, is an orally active vitamin D receptor (VDR) agonist with a Kd of 0.53 nM. Inecalcitol can induce cell apoptosis and has potent anticancer activities[1][2][3][4].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Vitamin D Related >> VD/VDR

[Target]

Kd: 0.53 nM (vitamin D receptor (VDR))[2]

[In Vitro]

Inecalcitol (0.1-10 nM; 48 hours) treatment of LNCaP cells results in decreased expression of both protein and mRNA of Pim-1 in a dose-dependent manner. Inecalcitol (0.1-10 nM; 48 hours) also decreases ETV1 expression levels in a dose-dependent manner[1]. Inecalcitol (10-14 days) inhibits the growth of LNCaP and HL-60 cells with ED50 values of 4.0 nM and 0.28 nM, respectively[1]. Western Blot Analysis[1] Cell Line: LNCaP cells Concentration: 0.1 nM, 1 nM, 10 nM Incubation Time: 48 hours Result: Resulted in decreased expression of both protein and mRNA of Pim-1 in a dose-dependent manner.

[In Vivo]

Inecalcitol (1.3 mg/kg; i.p.; 3 times per week; for 42 days) inhibits androgen-responsive prostate cancer growth in vivo[1]. Pharmacokinetic studies show that plasma half-life of Inecalcitol (C57Bl/6J mice; 1.3 mg/kg; i.p.) is 18.3 minutes in mice[1]. Animal Model: Male BNX nu/nu mice (8 weeks of age) injected with LNCaP cells[1] Dosage: 1.3 mg/kg Administration: i.p.; 3 times per week; for 42 days Result: Inhibited androgen-responsive prostate cancer growth in vivo.

[References]

[1]. Ryoko Okamoto, et al. Inecalcitol, an analog of 1α,25(OH)(2) D(3) , induces growth arrest of androgen-dependent prostate cancer cells. Int J Cancer. 2012 May 15;130(10):2464-73.

[2]. L Verlinden, et al. Interaction of two novel 14-epivitamin D3 analogs with vitamin D3 receptor-retinoid X receptor heterodimers on vitamin D3 responsive elements. J Bone Miner Res. 2001 Apr;16(4):625-38.

[3]. Jacques Medioni, et al. Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients. Clin Cancer Res. 2014 Sep 1;20(17):4471-7.

[4]. Yingyu Ma, et al. Inecalcitol, an analog of 1,25D3, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system. Cell Cycle. 2013 Mar 1;12(5):743-52.