Seocalcitol-EB-1089-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESeocalcitolCat. No.: HY-32341CAS No.: 134404-52-7Synonyms: EB 1089分式: CHO分量: 454.68作靶點: VD/VDR作通路: Vitamin D Related儲存式: 4C, protect from light, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 month (protect fromligh

2、t, stored under nitrogen)溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (109.97 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.1993 mL 10.9967 mL 21.9935 mL5 mM 0.4399 mL 2.1993 mL 4.3987 mL10 mM 0.2199 mL 1.0997 mL 2.1993 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實

3、驗 請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.50 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.50 mM); Clear solut

4、ion1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Seocalcitol種 vitamin D 類似物，作于瘤 MG-63 細胞，結(jié)合 vitamin D 受體蛋，Kd 為 0.27nM。IC50 & Target Kd: 0.27 nM (vitamin D receptor) 1體外研究 Seocalcitol (EB 1089) is a stimulators of osteoclast recruitment in murine bone marrow cultures, with E

5、C50 at0.1 nM. Seocalcitol stimulates bone resorption with an estimated EC50 at 0.03 nM 1. Seocalcitol (EB 1089)elicites a dose-dependent induction of 24-hydroxylase mRNA in the kidney (EC50=0.40.13). In the kidney,Kd values for Seocalcitol is 0.480.04 nM. However, in the intestine, the Kd for Seocal

6、citol is 1.430.19 nM)2. Seocalcitol (0.1-10 nM) induces cell differentiation in a dosedependent manner. A higher differentiatingactivity is observed for 1 nM Seocalcitol (EB 1089) than for 1 nM VD3.體內(nèi)研究 Seocalcitol (EB1089), a synthetic vitamin D analog, exhibits reduced hypercalcemic activity relat

7、ive to1,25(OH)2VD3. In another study, long-term intraperitoneal (IP) administration of Seocalcitol at a dose of 0.5g/kg body weight every other day in C3H/Sy mice exertes a very strong inhibitory effect on hepatocellularcarcinoma (HCC) development 4. Seocalcitol (EB 1089) is administered daily to po

8、stnatal rats from 4 to 12days of age (P4 to P12) by intraperitoneal injection at either 0.38 or 1.25 g/kg body weight (BW)/day. Onlythe highest dose of Seocalcitol (1.25 g/kg BW) causes a significant reduction in weight gain whenadministered alone or in conjunction with Dexamethasone, all-trans reti

9、noic acid (RA), or retinoic acid 5.PROTOCOLKinase Assay 1 Vitamin D receptor protein is prepared from cultures of human osteosarcoma cell line MG-63. Suspensions of5107 cells/mL are homogenized, sonicated, and centrifuged at 30,000g for 1 h at 4C. The presence of the1,25(OH)2D3 receptor is verified

10、by sucrose density gradient analysis. The supernatants are adjusted to 2mg protein/mL and used for binding studies. Samples of 500 L are incubated with 10,000 dpm 3H1,25(OH)2D3 (180 Ci/mmol) and increasing concentrations of 1,25(OH)2D3 or vitamin D3 analogs are added.After incubation for 60 min at 2

11、2C, bound and free 3H1,25(OH)2D3 are separated on dextran-coatedcharcoal. Each compound is tested in three separate experiments 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 3 This fluorescent dye allowed to determine ROS release in HL60

12、cells, untreated or treated VD3 orSeocalcitol. Briefly, after treatment, HL60 cells are washed and re-suspended at 106 cells/mL in RPMI-1640without FCS and phenol red. Then, 10 M H2-DCFDA probe is added to each plate at a final volume of 2 mL.Cells are incubated for 45 min at 37C in the dark. A seco

13、nd wash is made before the fluorescence analysisusing spectrometer at 488 nm intensity excitation ex and 516 nm emission em. Results, in arbitraryfluorescence units (AFU), are expressed according to the ratio (AFU-treated cells)/(AFU control cells)1003.MCE has not independently confirmed the accurac

14、y of these methods. They are for reference only.Animal Mice 4Administration 45 Six- to eight-week-old male BALB/c NU/Nu mice are inoculated subcutaneously with 106 SKHEP-1 cells into2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEthe right flank. Twenty-four hours after inoculation, mice are random

15、ly assigned to a control group (n=10) orthe treatment groups (n=10), receiving 0.02, 0.1 or 0.5 g/kg per day of Seocalcitol (intraperitoneal or oral onalternate days). Control animals receive propylene glycol alone. Tumor size is measured using verniercalipers every third day and the volumes are est

16、imated using the formula 0.5length(width)2. Animalsreceive sterile food and water.Rats 5Newborn Sprague-Dawley rat pups are randomly assigned to 1 of 6 treatment groups, consisting of dailyintraperitoneal injections of the vitamin D analogue Seocalcitol (0.38 or 1.25 g/kg body weight) alone, or inco

17、mbination with all-trans retinoic acid (RA; 500 g/kg body weight) and/or Dexamethasone (DEX; 0.25 g/day) in a 322 factorial design. Seocalcitol and RA injections are conducted on P3 through P12, whereasDexamethasone is administered on P4 through P12. Seocalcitol is prepared for injections in a quant

18、itysufficient for all injections by dilution from a stock solution (4 mM in isopropanol) into the carrier Solutol HS15 (BASF). Solutol-diluted Seocalcitol is stored as aliquots in sealed glass vials under nitrogen gas at 4C,with daily injections conducted with freshly unsealed aliquots of Seocalcito

19、l. Stock solutions of RA (50 mg/mLDMSO are stored under nitrogen at 80C and prepared for injection by dilution of freshly thawed aliquotsinto cottonseed oil (2 g/L). A Dexamethasone stock solution (10 mg/mL ethanol) is stored under nitrogen at4C and prepared fresh for daily injections in 0.9% NaCl (

20、0.25 g/L). All rats receive equivalent volumes ofthe 3 carrier solutions employed (solutol, cottonseed oil, 0.9% NaCl). Seocalcitol and RA are administered asa 2-phase solution via a 10 L injection using a 20 L glass-barreled syringe and a 28-gauge needle,whereas Dexamethasone is administered in a s

21、eparate 10 L injection.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Oncotarget. 2016 Sep 20;7(38):62240-62254.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Wiberg K, et al. Studies on two new vitamin D analogs, EB

22、1089 and KH 1060: effects on bone resorption and osteoclast recruitment invitro. Bone. 1995 Oct;17(4):391-5.2. Roy S, et al. Comparative effects of 1,25-dihydroxyvitamin D3 and EB 1089 on mouse renal and intestinal 25-hydroxyvitamin D3-24-hydroxylase. J Bone Miner Res. 1995 Dec;10(12):1951-9.3. Bondza-Kibangou P