GGTI298 - Ras 抑制劑 - 生命科學試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGGTI298Cat. No.: HY-100876CAS No.: 180977-44-0分式: CHNOS分量: 479.63作靶點: Ras作通路: GPCR/G Protein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 : 100 mg/mL (208.49 mM; Need ultrasonic)H2O : 40% P

2、EG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.21 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 (5.21 mM); Suspended solution; Need ultrasonic3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5

3、.21 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 GGTI298是有效的 GGTase I 抑制劑，能夠抑制 geranylgeranylated Rap1A 的過程，對 farnesylated Ha-Ras的過程也有定影響，在體內(nèi)，IC50 值分別為 3 和 20 M。IC50 & Target IC50: 3 M (Rap1A, in vivo), 20 M (Ha-Ras, in vivo) 3體外研究 Both RhoA inhibitor (GGTI298) and ROCK inhibitor (H1152) significantly

4、reduce cAMP agonist-stimulatedIK(ap), whereas the latter additionally reduces colocalization of KCNN4c with the apical membrane markerwheat germ agglutinin in T84WT cells 1. Knockdown of DR4 abolishes NF-B activation, leading tosensitization of DR5-dependent apoptosis induced by the combination of G

5、GTI298 and TRAIL.GGTI298/TRAIL activates NF-B and inhibits Akt. knockdown of DR5, preventes GGTI298/TRAIL-induced IB and p-Akt reduction, suggesting that DR5 mediates reduction of IB and p-Akt induced byGGTI298/TRAIL. In contrast, DR4 knockdown further facilitates GGTI298/TRAIL-induced p-Akt reducti

6、on 2.體內(nèi)研究 The vivo mouse ileal loop experiments show fluid accumulation is reduced in a dose-dependent manner byTRAM-34, GGTI298, or H1152 when injected together with cholera toxin into the loop 1.PROTOCOLKinase Assay 2 The given cells are lysed with Reporter Lysis Buffer and subjected to luciferase

7、 activity assay usingLuciferase Assay System in a luminometer. Relative luciferase activity is normalized to protein content.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 Cells are seeded in 96-well cell culture plates and treated the nex

8、t day with the agents indicated. The viablecell number is determined using the sulforhodamine B assay.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal The ileal loop experiment is performed in 6-8-week-old mice by a modified rabbit ileal loop assa

9、y. FollowingAdministration 1 gut sterilization, the animals are kept fasted for 24 h prior to surgery and fed only water ad libitum.Anesthesia is induced by a mixture of ketamine (35 mg/kg of body weight) and xylazine (5 mg/kg of bodyweight). A laparotomy is performed, and the experimental loops of

10、5-cm length are constricted at the terminalileum by tying with non-absorbable silk. The following fluids are instilled in each loop by means of atuberculin syringe fitted with a disposable needle through the ligated end of the loop as the ligatured istightened: pure CT (1 g; positive control), salin

11、e (negative control), CT (1 g) + TRAM-34 (differentconcentrations in M as indicated in Fig. 7), CT (1 g) + H1152 (1 M), and CT (1 g) + GGTI298 (differentconcentrations in M), a specific inhibitor of Rap1A. The intestine is returned to the peritoneum, and the miceare sutured and returned to their cag

12、es. After 6 h, these animals are sacrificed by cervical dislocation, andthe loops are excised. The fluid from each loop is collected, and the ratio of the amount of fluid contained inthe loop with respect to the length of the loop (fluid accumulation ratio in g/cm) is calculated as a reflection of2/

13、3 Master of Small Molecules 您邊的抑制劑師www.MedChemEthe efficacy of various inhibitors.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Sheikh IA, et al. The Epac1 signaling pathway regulates Cl- secretion via modulation of apical KCNN4c channels

14、 in diarrhea. J BiolChem. 2013 Jul 12;288(28):20404-152. Chen S, et al. Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of geranylgeranyltransferase I inhibition-mediatedaugmentation of TRAIL-induced apoptosis. Mol Cancer. 2010 Jan 29;9:23.3. McGuire TF, et al. Platelet-derived growth factor receptor tyrosine phosphorylation requires protein geranylgeranylation but notfarnesylation. J Biol Chem. 1996 Nov 1;2