Bisindolylmaleimide-I-GF109203X-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBisindolylmaleimide ICat. No.: HY-13867CAS No.: 133052-90-1Synonyms: GF109203X; Go 6850分式: CHNO分量: 412.48作靶點: PKC作通路: Epigenetics; TGF-beta/Smad儲存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect fro

2、mlight)溶解性數據體外實驗 DMSO : 32 mg/mL (77.58 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.4244 mL 12.1218 mL 24.2436 mL5 mM 0.4849 mL 2.4244 mL 4.8487 mL10 mM 0.2424 mL 1.2122 mL 2.4244 mL請根據產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。體內實驗 請根據您的實驗動物和給藥式選擇適當

3、的溶解案，配制前請先配制澄的儲備液，再依次添加助溶劑(為保證實驗結果的可靠性，體內實驗的作液，建議您現現配，當天使；澄的儲備液可以根據儲存條件，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 40% PEG300 5% Tween-80 45% salineSolubility: 1 mg/mL (2.42 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 Bisindolylmaleimide I (

4、GF109203X)種度選擇，可滲透細胞，可逆的 PKC抑制劑，Ki 值為14 nM。IC50 & Target Bovine brain PKC PKCII PKCI PKC10 nM (IC50) 16 nM (IC50) 17 nM (IC50) 20 nM (IC50)PKC FDGFR20 nM (IC50) 65 M (IC50)體外研究 Bisindolylmaleimide I is a competitive inhibitor with respect to ATP (Ki=14 nM) and displays high selectivity forPKC as com

5、pared to five different protein kinases. GF 109203X efficiently prevents PKC-mediatedphosphorylations of an Mr=47,000 protein in platelets and of an Mr=80,000 protein in Swiss 3T3 cells. GF109203X inhibits collagen- and a-thrombin-induced platelet aggregation as well as collagen-triggered ATPsecreti

6、on. However, ADP-dependent reversible aggregation is not modified. In Swiss 3T3 fibroblasts, GF109203X reverses the inhibition of epidermal growth factor binding induced by phorbol 12,13-dibutyrate andprevents 3H thymidine incorporation into DNA, only when this is elicited by growth promoting agents

7、 whichactivate PKC 1.體內研究 Pial arteriole diameter changes are monitored using a closed cranial window in vivo microscopy technique. Thepial arteriole dilatory response associated with SNS is decreased by 45%, when comparing DM vs either ND orTR rats. Also, pial arteriolar dilations to topical KCl an

8、d NS1619 are largely attenuated in DM rats, but not inND or TR animals. These responses are completely restored by the acute application of Bisindolylmaleimide Ito the brain surface. The PKC inhibitor has no effect on vascular responses in normoglycemic and TR animals.In conclusion, DM-associated ch

9、ronic impairment of neurovascular coupling may be readily reversed by aPKC-/ inhibitor or prevented via pancreatic islet transplantation. Specific PCK isoforms (/) are believedto be mechanistically linked to the neurovascular uncoupling seen with hyperglycemia 2.PROTOCOLKinase Assay 1 Assay of PKC i

10、s arrayed by measuring 32Pi transferred from -32Pi ATP to lysine-rich histone type Ill-s. Thereaction mixture (80 L) contains 50 mM Tris-HCI, pH 7.4. 100 M CaCl2, 10 mM MgCI2, 37.5 g/mL histonetype Ill-s, l0 M -32Pi ATP (1250cpm/pmol), 31 M bovine brain phosphatidylserine and 0.5 M 1,2 sn-dioleylgly

11、cerol. 15 L of purified PKC (final concentration in assay 0.38 g/mL) is added to the incubationmixture. After 10 minutes, the reaction is stopped by addition of at 30 L of casein 30 mg/mL and 0.9 mL of12% trichlomacetic acid 1.MCE has not independently confirmed the accuracy of these methods. They a

12、re for reference only.Animal Three sets of Lewis rats is used for this study: 1) euglycemic 46 month old non-diabetic controls (ND group,Administration 2 n=11); 2) streptozotocin (STZ)-treated diabetic rats (6 month old, 4 months post-STZ) (DM group, n=6); and3) STZ-treated diabetic animals, subject

13、ed to pancreatic islet transplantation soon after the establishment ofthe diabetic model, studied 100110 days after the transplant (TR group, n=7) 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發(fā)表的科研獻2/3 Master of Small Molecules 您邊的抑制劑師www.MedC

14、hemE Food Chem Toxicol. 2019 Mar;125:46-54. Front Endocrinol (Lausanne). 2018 Nov 30;9:721. Biosci Rep. 2019 Apr 26;39(4). pii: BSR20182293.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Toullec D, et al. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem. 1991 Aug25;266(24):15771-81.2. Vetri F, et al. Impairment of neurovascular coupling in Type 1 Diabetes Mellitus in rats is prevented by pancreatic islet transplantationand reversed by a semi-selective PKC inhibitor. Brain Res. 2