1447711-33-2Relevant articles and documents
Sulfonyl-containing phenyl-pyrrolyl pentane analogues: Novel non-secosteroidal vitamin D receptor modulators with favorable physicochemical properties, pharmacokinetic properties and anti-tumor activity
Kang, Zi-Sheng,Wang, Cong,Han, Xiao-Lin,Wang, Bin,Yuan, Hao-Liang,Hou, Si-Yuan,Hao, Mei-Xi,Du, Jun-Jie,Li, Yan-Yi,Zhou, An-Wei,Zhang, Can
, p. 1174 - 1191 (2018)
Modulating the vitamin D receptor (VDR) is an effective way to treat for cancer. We previously reported a potent non-secosteroidal VDR modulator (sw-22) with modest anti-tumor activity, which could be due to its undesirable physicochemical and pharmacokinetic properties. In this study, we investigated the structure-activity and structure-property relationships around the 2′-hydroxyl group of sw-22 to improve the physicochemical properties, pharmacokinetic properties and anti-tumor activity. Compounds 19a and 27b, the potent non-secosteroidal VDR modulators, were identified as the most effective molecules in inhibiting the proliferation of three cancer cell lines, particularly breast cancer cells, with a low IC50 via the distribution of cell cycle and induction of apoptosis by stimulating the expression of p21, p27 and Bax. Further investigation revealed that 19a and 27b possessed favorable rat microsomal metabolic stability (2.22 and 2.3 times, respectively, more stable than sw-22), solubility (43.9 and 50.2 times, respectively, more soluble than sw-22) and in vivo pharmacokinetic properties. In addition, 19a and 27b showed excellent in vivo anti-tumor activity without cause hypercalcemia, which is the main side effect of marketed VDR modulators. In summary, the favorable physicochemical properties, pharmacokinetic properties and anti-tumor activity of 19a and 27b highlight their potential therapeutic applications in cancer treatment.
Novel Nonsecosteroidal Vitamin D Receptor Modulator Combined with Gemcitabine Enhances Pancreatic Cancer Therapy through Remodeling of the Tumor Microenvironment
Kang, Zisheng,Wang, Cong,Tong, Yu,Li, Yanyi,Gao, Yi,Hou, Siyuan,Hao, Meixi,Han, Xiaolin,Wang, Bin,Wang, Qianqian,Zhang, Can
, p. 629 - 643 (2021)
In a pancreatic tumor microenvironment, activated pancreatic stellate cells (PSCs) produce extracellular matrix (ECM) to form a barrier to drug penetration. Moreover, the interaction between cancer cells and activated PSCs promotes the tumor growth. Vitam
Design, Synthesis, and Antifibrosis Activity in Liver of Nonsecosteroidal Vitamin D Receptor Agonists with Phenyl-pyrrolyl Pentane Skeleton
Wang, Cong,Wang, Bin,Xue, Lingjing,Kang, Zisheng,Hou, Siyuan,Du, Junjie,Zhang, Can
, p. 10573 - 10587 (2018)
Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM) components and results in impaired liver function. Vitamin D plays a critical role in the development of liver fibrosis as it inhibits transforming growth factor β1 (TGF
Discovery of novel nonsteroidal VDR agonists with novel diarylmethane skeleton for the treatment of breast cancer
Wang, Cong,Wang, Bin,Hou, Siyuan,Xue, Lingjing,Kang, Zisheng,Du, Junjie,Li, Yanyi,Liu, Xuwentai,Wang, Qianqian,Zhang, Can
, p. 787 - 803 (2019/01/04)
Vitamin D receptor (VDR) is recognized as a potential target for the treatment of breast cancer which is the most common malignancy among women in the world. In this study, a series of nonsecosteroidal VDR agonists with a novel diarylmethane skeleton was
Further Developments of the Phenyl-Pyrrolyl Pentane Series of Nonsteroidal Vitamin D Receptor Modulators as Anticancer Agents
Hao, Meixi,Hou, Siyuan,Xue, Lingjing,Yuan, Haoliang,Zhu, Lulu,Wang, Cong,Wang, Bin,Tang, Chunming,Zhang, Can
, p. 3059 - 3075 (2018/04/23)
The vitamin D3 receptor (VDR), which belongs to the nuclear-receptor superfamily, is a potential molecular target for anticancer-drug discovery. In this study, a series of nonsteroidal vitamin D mimics with phenyl-pyrrolyl pentane skeletons wit
Design, synthesis and biological evaluation of nonsecosteroidal vitamin D3receptor ligands as anti-tumor agents
Wang, Bin,Hao, Meixi,Zhang, Can
supporting information, p. 1428 - 1436 (2017/03/08)
1α,25-dihydroxyvitamin D3(1,25-(OH)2D3, also known as calcitriol), the active form of vitamin D3, is being increasingly recognized for cancer therapy. Our previous work showed that phenyl-pyrrolyl pentane analogs, which mimicked anti-proliferative activities against several cancer cell lines of the natural secosteroidal ligand 1,25-(OH)2D3. Here, in order to optimize the structural features and discover more potent derivative, a series of nonsecosteroidal vitamin D3receptor (VDR) ligands bearing acetylene bond linker was designed, synthesized and evaluated. Most of them showed moderate to good binding affinities and agonistic activities. Especially, compound 19f displayed the most anti-proliferative activities against MCF-7 and PC-3 cells with the IC50values of 1.80 and 5.35 μM, respectively, which was comparable to positive control 1,25-(OH)2D3. Moreover, compound 19f exhibited reduced toxicity against human normal liver cell line (L02) compared with the parental compound 7. Besides, the preliminary structure–activity relationships (SARs) were also analyzed.
Novel nonsecosteroidal VDR agonists with phenyl-pyrrolyl pentane skeleton
Shen, Wei,Xue, Jingwei,Zhao, Zekai,Zhang, Can
, p. 768 - 778 (2013/10/22)
In order to find the vitamin D receptor (VDR) ligand whose VDR agonistic activity is separated from the calcemic activity sufficiently, novel nonsecosteroidal analogs with phenyl-pyrrolyl pentane skeleton were synthesized and evaluated for the VDR binding
