Trametinib(DMSOsolvate) , ≥99% , 1187431-43-1

CAS NO.：1187431-43-1

Empirical Formula: C28H29FIN5O5S

Molecular Weight: 693.53

MDL number: MFCD21609250

PRODUCT Properties

• storage temp.: Store at -20°C
• solubility: insoluble in EtOH; insoluble in H2O; ≥11.2 mg/mL in DMSO with gentle warming and ultrasonic
• form: solid
• color: White to off-white
• InChIKey: OQUFJVRYDFIQBW-UHFFFAOYSA-N
• SMILES: S(=O)(C)C.N(C1C=CC(I)=CC=1F)C1N(C(=O)C(C)=C2N(C3C=CC=C(NC(=O)C)C=3)C(=O)N(C3CC3)C(=O)C=12)C

Description and Uses

In May 2013, the US FDA approved trametinib (also referred to as GSK1120212 and JTP-74057), for the treatment of patients with unresectable or metastatic melanoma with BRAF^V600e or BRAF^V600K mutations as detected by an FDA-approved test. Extensive lead optimization led to the identification of trametinib which is a potent ATP noncompetitive inhibitor of MEK1 and MEK2 (IC₅₀ =0.7 and 0.9 nM, respectively, with initially unphosphorylated MEK). It also showed inhibitory activity in ACHN and HT-29 cancer cell lines (IC_50s of 9.8 and 0.57 nM, respectively). Consistent with its in vitro activity, trametinib showed significant antitumor activity in a KRAS^G12S A549 tumor xenograft model where near to complete tumor growth inhibition (TGI) was observed at 5.0 and 2.5 mg/kg (92% and 87% TGI, respectively). Broad antitumor activity was seen in other xenograft models as well. A synthetic route to trametinib that employs a base catalyzed rearrangement of a pyrido[2,3-d]pyrimidine core to pyrido[4,3-d]pyrimidine, as a key step has been reported.

Trametinib (DMSO Solvate) is a highly potent and selective MEK inhibitor with significant antitumor activity.

Safety

• Symbol(GHS): GHS08,GHS07,GHS09
• Signal word: Danger
• Hazard statements: H361-H410-H317-H372
• Precautionary statements: P201-P202-P281-P308+P313-P405-P501-P261-P272-P280-P302+P352-P333+P313-P321-P363-P501-P260-P264-P270-P314-P501-P273-P391-P501