Cyclopamine-11-Deoxojervine-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECyclopamineCat. No.: HY-17024CAS No.: 4449-51-8Synonyms: 11-Deoxojervine分式: CHNO分量: 411.62作靶点: Hedgehog作通路: Stem Cell/Wnt储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 Ethanol : 16.67 mg/mL (40.5

2、0 mM; Need ultrasonic)DMSO : 5 mg/mL (12.15 mM; Need ultrasonic and warming)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 0.5 mg/mL (1.21 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 0.5 mg/mL (1.21 mM); Clear s

3、olution3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 0.5 mg/mL (1.21 mM); Clear solution4. 请依序添加每种溶剂： 10% EtOH 90% (20% SBE-CD in saline)Solubility: 1.67 mg/mL (4.06 mM); Suspended solution; Need ultrasonic5. 请依序添加每种溶剂： 10% EtOH 90% corn oilSolubility: 1.43 mg/mL (3.47 mM); Clear solutionBIOLOGICAL

4、 ACTIVITY物活性 Cyclopamine是Hedgehog 通路的拮抗剂，在细胞实验中的 IC50 为 46 nM。IC50 & Target IC50: 46 nM (Hedgehog, in Hh cell assay) 1体外研究 Treatment with small molecule Hh inhibitors such as HhAntag and the natural product Cyclopamine, bothbinding to Smo, induces tumor remission in a genetic mouse model of medullob

5、lastoma 1. Cyclopamine is aHedgehog (Hh) pathway antagonist. Cyclopamine suppresses cell growth. Cyclopamine (3 M) suppressionof Hh pathway activity and growth in digestive tract tumour cell lines correlates with expression ofPTCHmRNA 2. Cyclopamine is a steroidal alkaloid that inhibits Hh signallin

6、g through direct interaction withSmo 3.体内研究 Cyclopamine causes durable regression of xenograft tumors. Tumors in Cyclopamine-treated animals,regress completely by 12 days 2. Cyclopamine (1.2 mg) treatment blocks tumour formation of humanpancreatic adenocarcinoma cells after transplantation into nude

7、 mice 3.PROTOCOLCell Assay 2 Cells are cultured in triplicate in 96-well plates in assay media to which 5E1 monoclonal antibody, ShhNpand/or Cyclopamine (3 M) are added at 0 h at concentrations indicated in the main text. Viable cell mass isdetermined by optical density measurements at 490 nm (OD490

8、) at 2 and 4 days using the CellTiter96colorimetric assay. Relative growth is calculated as OD (day 4)-OD (day 2)/OD (day 2) 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administration 3 A total of 0.1 mL Hanks balanced salt solution a

9、nd matrigel (1:1) containing 2106 cells is injectedsubcutaneously into CD-1 nude mice. Tumors are grown for 4 days to a minimum volume of 125 mm3;treatment is initiated simultaneously for all subjects. Mice are injected subcutaneously with vector alone(triolein:ethanol 4:1 v/v) or a Cyclopamine susp

10、ension (1.2 mg per mouse in triolein:ethanol 4:1 v/v) daily for7 days. At the end of the treatment period, tumours are excised from mice, weighed and then fixed for 3 h at4C with 4% paraformaldehyde, embedded in paraffin wax and sectioned (6 m). Apoptotic cells areidentified by TUNEL using recombina

11、nt Tdt. Sections are then counterstained with eosin. Eight 20-magnified fields from regions corresponding to the exterior, middle and interior of two control and two2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEcyclopamine-treated tumours are chosen at random. We counted the number of TUNEL-posit

12、ive nucleimanually. Haematoxylin/eosin staining is done.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 FASEB J. 2018 Oct;32(10):5703-5715. J Genet Genomics. 2018 May 20;45(5):237-246. Int J Nanomedicine. 2017 Apr 20;12:3267-3280. Front Phar

13、macol. 2018 Jun 26;9:674. Life Sci. 2017 Dec 15;191:82-89.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Peukert S, et al. Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonistsinhibiting the Hedgehog signaling pathw

14、ay. Bioorg Med Chem Lett, 2009, 19(2), 328-331.2. Berman DM, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature, 2003,425(6960), 846-851.3. Thayer SP, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature, 2003, 425(6960), 851-856.4. Ma W, et al. Reduced Smoothened level rescued A-induced memory deficits and neuronal inflammation in animal models ofAlzheimers disease. J Genet Genomics. 2018 May