Dabrafenib-GSK2118436A-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDabrafenibCat. No.: HY-14660CAS No.: 1195765-45-7Synonyms: GSK2118436A; GSK2118436分式: CHFNOS分量: 519.56作靶點: Raf作通路: MAPK/ERK Pathway儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 33 mg/mL (

2、63.52 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9247 mL 9.6235 mL 19.2471 mL5 mM 0.3849 mL 1.9247 mL 3.8494 mL10 mM 0.1925 mL 0.9624 mL 1.9247 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)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?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

3、可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)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 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.81 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.81 mM); Clear solution1/3 Master of Small Molecules 您

4、邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.81 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Dabrafenib是ATP競爭型的 Raf 抑制劑，抑制 C-Raf 和 B-RafV600E 的 IC50 分別為 5 nM 和 0.6 nM。IC50 & Target BRafV600E CRAF0.6 nM (IC50) 5 nM (IC50)體外研究 Dabrafenib (GSK2118436, 1 M) with 0.01 M GSK1

5、120212 inhibits more than 90% of cell growth in theNRAS mutant clones. GSK2118436 is sufficient to reduce S6P phosphorylation in A375 1. Dabrafenibsuppresses the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers,adhesion/migration of leukocytes, and activation and

6、/or production of nuclear factor-B, tumor necrosisfactor-, and interleukin-6 2. Dabrafenib inhibits the release of HMGB1 and downregulates HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) inhuman endothelial cells 3.體內(nèi)研究 Dabrafenib-treated females

7、 have mostly immature reproductive tracts with no evidence of ovulation, similarto age-matched controls; however, DAB-treated females have keratinized and histologically open vaginas 5.PROTOCOLCell Assay 1 For longer term proliferation assays, cells are plated and treated with compound or combinatio

8、n ofcompounds in RMPI-1640 containing 10% FBS for 12 days. Compound treatments are replaced at leastonce during the assay. After 12 days, cells are stained with 0.5% methylene blue in 50% ethanol. Images arecaptured using flatbed scanner.MCE has not independently confirmed the accuracy of these meth

9、ods. They are for reference only.Animal The rat pups selected as the test system are derived from 26 10-week-old, time-mated, virus-antibody-freeAdministration 5 SD (Crl:CDSD) female rats. Mated females are observed for natural deliveries from Day 20 to 23 pc (dayparturition completed is designated

10、PND 0). Litter examinations are conducted when parturition is complete,on PNDs 3 and 6, and included gender identification, individual pup weights, and external morphologicexaminations. Parturient dams and their litters are selected for study based on clinical signs and bodyweights, and selected dam

11、s and their litters are randomized into study groups based on clinical observationsand PND 3 litter mean body weights. On PND 3 or 4, litters are culled to four males and five females, withminimal fostering only when necessary to obtain the desired sex ratio, such that natural litters are maintained

12、as much as possible. Records are kept of fostered pups of original and foster dams. All pups are identified bypaw tattoo. To the extent possible, nonlittermates are assigned to subsets. DAB is formulated as asuspension in vehicle, 0.5% hydroxypropylmethylcellulose K15M, and 0.1% (v/v) Tween80 in pur

13、ified water,and is given to juvenile male and female rats orally by gavage at a dose volume of 5 ml/kg, based on dailybody weight.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMCE 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 Science. 2017

14、Dec 1;358(6367). Cell. 2018 Aug 9;174(4):843-855.e19. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Mol Cell. 2019 Jan 3;73(1):7-21.e7. Mol Ther Oncolytics. 2019 Feb 5;12:235-245.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Greger JG, et al. Combinations of BRAF, MEK,

15、and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitorGSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther, 2012, 11(4), 909-920.2. Lee S, et al. Anti-inflammatory effects of dabrafenib on polyphosphate-mediated vascular disruption. Chem Biol Interact. 2016

16、Jul 22.3. Jung B, et al. Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses. BMB Rep. 2016 Apr;49(4):214-9.4. Alexander M Menzies, et al. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Devel Ther. 2012; 6:391405.5. Posobiec LM, et al. Early Vaginal Opening in Juvenile Female Rats Given BRAF-Inhibitor Dabrafenib Is Not Associated with EarlyPhysiologic Sexual Maturation. Birth Defects R