Trametinib DMSO solvate

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效且高度特异性的 MEK1/2 抑制剂，IC50 为 0.92 nM/1.8 nM。

A potent and highly specific MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM; exhibits no inhibition on the kinase activities of c-Raf, B-Raf, ERK1/2.Skin Cancer Approved(In Vitro):In BRAF mutant SK-MEL-28 cells and KRAS mutant HCT116 cells, Trametinib (GSK1120212;JTP-74057) DMSO solvate causes dose-dependent inhibition of ERK1/2 phosphorylation as well as dose-dependent growth inhibition. In both SK-MEL-28 and HCT116 cells, Trametinib DMSO solvate inhibits 50% p-ERK1/2 at nearly equivalent concentrations (0.8 and 1.8 nM, respectively). However, as the slopes of the curves reflect, in SK-MEL-28 cells, Trametinib DMSO solvate inhibits 90% p-ERK1/2 at a lower concentration (3.4 nM) than in HCT116 (33.3 nM). Furthermore, in both cell lines, 50% growth inhibition is only achieved at concentrations Trametinib DMSO solvate that produces near complete ERK1/2 inhibition (85 and 90%, respectively). (In Vivo):Trametinib (GSK1120212;JTP-74057) DMSO solvate is evaluated in vivo in an A549 (KRAS mutant cell line) xenograft model, orally dosing daily for 21 days (qd×21). In this study, near complete tumor growth inhibition is observed at 5.0 and 2.5 mg/kg [92 and 87% tumor growth inhibition (TGI), respectively] and to a lesser degree at 0.5 and 0.1 mg/kg (62 and 58% TGI). Although 5 mg/kg is the maximally tolerated dose (MTD) in this study, 3 mg/kg is the typically observed MTD. Dose-dependent antitumor activity with Trametinib DMSO solvate treatment has been similarly reported for several other KRAS and BRAF mutant tumor models.

In BRAF mutant SK-MEL-28 cells and KRAS mutant HCT116 cells, Trametinib (GSK1120212;JTP-74057) DMSO solvate causes dose-dependent inhibition of ERK1/2 phosphorylation as well as dose-dependent growth inhibition. In both SK-MEL-28 and HCT116 cells, Trametinib DMSO solvate inhibits 50% p-ERK1/2 at nearly equivalent concentrations (0.8 and 1.8 nM, respectively). However, as the slopes of the curves reflect, in SK-MEL-28 cells, Trametinib DMSO solvate inhibits 90% p-ERK1/2 at a lower concentration (3.4 nM) than in HCT116 (33.3 nM). Furthermore, in both cell lines, 50% growth inhibition is only achieved at concentrations Trametinib DMSO solvate that produces near complete ERK1/2 inhibition (85 and 90%, respectively).

Trametinib (GSK1120212;JTP-74057) is evaluated in vivo in an A549 (KRAS mutant cell line) xenograft model, orally dosing daily for 21 days (qd×21). In this study, near complete tumor growth inhibition is observed at 5.0 and 2.5 mg/kg [92 and 87% tumor growth inhibition (TGI), respectively] and to a lesser degree at 0.5 and 0.1 mg/kg (62 and 58% TGI). Although 5 mg/kg is the maximally tolerated dose (MTD) in this study, 3 mg/kg is the typically observed MTD. Dose-dependent antitumor activity with Trametinib treatment has been similarly reported for several other KRAS and BRAF mutant tumor models.

GSK-1120212 DMSO solvate | Trametinib | JTP-74057 | GSK-1120212

MAPK/ERK Signaling

MEK

MEK

Cancer

Skin Cancer

1187431-43-1

693.5283

C28H29FIN5O5S

>98% (HPLC)

DMSO: ≥ 69 mg/mL (Need ultrasonic)

CC1=C2C(C(N(C3CC3)C(N2C4=CC(NC(C)=O)=CC=C4)=O)=O)=C(NC5=C(F)C=C(I)C=C5)N(C)C1=O.CS(C)=O

N-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide compound with (methylsulfinyl)methane (1:1)

(-20℃)

With Ice Pack

≥ 2 years