ZK 159222
目录号 : GC48271An antagonist of the vitamin D receptor
Cas No.:156965-15-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ZK 159222 is an antagonist of the vitamin D receptor (VDR).1,2 It stabilizes the VDR in an antagonistic conformation that prevents interaction with coactivator proteins.3 ZK 159222 inhibits VDR-mediated target gene activation when used at concentrations of 300 and 1,000 nM in reporter assays. Preincubation of preadipocytes with ZK 159222 (0.01 and 1 µM) decreases the secretion of IL-1β, IL-6, IL-8, CCL2, and RANTES induced by macrophage-conditioned medium (MacCM).4 It also decreases the secretion of these cytokines in preadipocytes prestimulated with MacCM and decreases MacCM-induced phosphorylation of p44/42 and p38 MAPK in preadipocytes.
1.Herdick, M., Steinmeyer, A., and Carlberg, C.Antagonistic action of a 25-carboxylic ester analogue of 1ɑ,25-dihydroxyvitamin D3 is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivatorsJ. Biol. Chem.275(22)16506-16512(2000) 2.Herdick, M., Steinmeyer, A., and Carlberg, C.Carboxylic ester antagonists of 1ɑ,25-dihydroxyvitamin D3 show cell-specific actionsChem. Biol.7(11)885-894(2000) 3.Bury, Y., Steinmeyer, A., and Carlberg, C.Structure activity relationship of carboxylic ester antagonists of the vitamin D3 receptorMol. Pharmacol.58(5)1067-1074(2000) 4.Zhu, J., and Wilding, J.P.H.The 1α,25(OH)2D3 analogs ZK159222 and ZK191784 show anti-inflammatory properties in macrophage-induced preadipocytes via modulating the NF-κB and MAPK signalingDiabetes Metab. Syndr. Obes.131715-1724(2020)
| Cas No. | 156965-15-0 | SDF | |
| Canonical SMILES | C=C1/C(C[C@@H](O)C[C@@H]1O)=C\C=C2CCC[C@@]3(C)[C@@]/2([H])CC[C@]3([H])[C@H](C)/C=C/[C@@H](O)C4(CC4)C(OCCCC)=O | ||
| 分子式 | C32H48O5 | 分子量 | 512.7 |
| 溶解度 | DMSO : 100 mg/mL (195.04 mM; Need ultrasonic) | 储存条件 | 4°C, protect from light, stored under nitrogen |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9505 mL | 9.7523 mL | 19.5046 mL |
| 5 mM | 0.3901 mL | 1.9505 mL | 3.9009 mL |
| 10 mM | 0.195 mL | 0.9752 mL | 1.9505 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Vitamin D analogs modulate the action of gonadal steroids in human vascular cells in vitro
Am J Hypertens 2000 Apr;13(4 Pt 1):396-403.PMID:10821342DOI:10.1016/s0895-7061(99)00203-4.
We have previously reported that estradiol (E2) and dihydrotestosterone (DHT) regulate cell growth in human umbilical arterial smooth muscle cells (SMC) and in an endothelial cell line (E304). In SMC both gonadal steroids stimulated DNA synthesis at low concentrations and suppressed 3[H] thymidine incorporation at high concentrations, whereas in E304 cells E2 and DHT dose dependently enhanced DNA synthesis. In both cell types gonadal steroids also induced the specific activity of creatine kinase BB (CK). Previous evidence suggets that the in vitro and in vivo CK responses to gonadal steroids in bone cells are upregulated by pretreatment with vitamin D analogs due to increased level of cellular estrogen receptors (ER). Here we analyzed the interaction of the vitamin D analogs hexafluorovitamin D (FL), JK-1624 F2-2 (JKF), and CB 1093 (CB) with gonadal steroids in regulating DNA synthesis and CK activity in human vascular cells in vitro. In E304 cells, daily treatment with FL, JKF, or CB (1 nmol/L for 3 days) increased DNA synthesis by 110 +/- 11%, 65 +/- 16%, and 88 +/- 23% respectively. In contrast, the same analogs inhibited 3[H] thymidine incorporation by 52 +/- 21%, 46 +/- 19%, and 50 +/- 10%, respectively, in SMC. In both cell types all three analogs increased CK by 25% to 75% and amplified the CK response to E2 and to DHT by twofold to threefold. In E304 cells the vitamin D analogs also increased DNA response to gonadal steroids from 50% to 60% to 200% to 280%. In SMC these analogs did not modify the DNA synthetic response to a low E2 concentration, but prevented the suppression of DNA synthesis exerted by high concentrations of E2 and DHT. Vitamin D inhibitors known to block cellular calcium mobilization, had no effect on the proliferative activity induced by vitamin D analogs. However, the inhibitor of the nuclear effects of vitamin D, ZK 159222, blocked the stimulatory effects of CB on DNA synthesis in E304 cells. Finally, both 1,25(OH)2 D3, and JKF decreased the expression of ERbeta proteins in SMC and increased the ERalpha isoform in E304 cells by 40% to 75%. The results indicate that vascular cells are targets for both vitamin D and gonadal steroid action and suggest a possible interaction between these hormones in the regulation of cell proliferation via modulation of vascular ER or interaction with proteins associated with ER.
Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns
Eur J Immunol 2006 Feb;36(2):361-70.PMID:16402404DOI:10.1002/eji.200425995.
Toll-like receptors (TLR) represent an ancient front-line defence system that enables the host organism to sense the presence of microbial components within minutes. As inducers of inflammation, TLR act as important triggers of distinct entities such as sepsis or autoimmune disease exacerbation. We report here that vitamin D3 [1alpha,25-dihydroxycholecalciferol, 1,25(OH)(2)D3] suppresses the expression of TLR2 and TLR4 protein and mRNA in human monocytes in a time- and dose-dependent fashion. Despite 1,25(OH)(2)D3-induced up-regulation of CD14, challenge of human monocytes with either LPS or lipoteichoic acid resulted in impaired TNF-alpha and procoagulatory tissue factor (CD142) production, emphasizing the critical role of TLR in the induction of inflammation. Moreover, reduced TLR levels in 1,25(OH)(2)D3-treated phagocytes were accompanied by impaired NF-kappaB/RelA translocation to the nucleus and by reduced p38 and p42/44 (extracellular signal-regulated kinase 1/2) phosphorylation upon TLR-ligand engagement. Both TLR down-regulation and CD14 up-regulation were substantially inhibited by the vitamin D receptor (VDR) antagonist ZK 159222, indicating that the immunomodulatory effect of 1,25(OH)(2)D3 on innate immunity receptors requires VDR transcription factor activation. Our data provide strong evidence that 1,25(OH)(2)D3 primes monocytes to respond less effectively to bacterial cell wall components in a VDR-dependent mechanism, most likely due to decreased levels of TLR2 and TLR4.
Regulation of Vitamin D hydroxylases gene expression by 1,25-dihydroxyvitamin D3 and cyclic AMP in cultured human syncytiotrophoblasts
J Steroid Biochem Mol Biol 2007 Jan;103(1):90-6.PMID:17079137DOI:10.1016/j.jsbmb.2006.07.010.
Human placenta synthesizes and metabolizes 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)/calcitriol] through the activity of 25-hydroxyvitamin D(3)-1alpha-hydroxylase (CYP27B1) and 1,25(OH)(2)D(3)-24-hydroxylase (CYP24A1), the two key enzymes for Vitamin D metabolism. In this study, calcitriol rapidly generated intracellular cAMP accumulation in cultured human syncytiotrophoblast cells, which in turn enhanced hCG secretion, a marker of trophoblast endocrine activity. The effects of 1,25(OH)(2)D(3) upon the expression of CYP27B1 and CYP24A1 were also investigated. 1,25(OH)(2)D(3) and activators of the PKA signaling system decreased the expression of CYP27B1, whereas increased CYP24A1 gene transcription. The use of a selective inhibitor of PKA (H-89) prevented the effects of calcitriol on CYP27B1 gene and hCG secretion, but not on CYP24A1 transcription. Addition of ZK 159222, a Vitamin D receptor (VDR) antagonist, blocked the calcitriol-mediated upregulation of 24-hydroxylase gene expression but did not affect calcitriol-induced downregulation of CYP27B1 gene or hCG stimulation. In addition, our study also demonstrated a role of calcitonin on Vitamin D hydroxylases gene regulation in placenta. The overall data suggest that calcitriol downregulates CYP27B1 expression via a cAMP-dependent signaling pathway, whereas upregulates 24-hydroxylase gene expression through a VDR-dependent mechanism.