Trametinib DMSO solvate

SKU: orb1226854

Description

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).\n(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.

Key Properties

• CAS Number: 1187431-43-1
• MW: 693.5283
• Purity: >98% (HPLC)
• Formula: C₂₈H₂₉FIN₅O₅S
• SMILES: 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
• Target: MEK
• Solubility: DMSO: ≥ 69 mg/mL (Need ultrasonic)

Bioactivity

• In Vivo:
  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.
• 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).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

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

Trametinib DMSO solvate

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Gene Symbol

MEK