TraMetinib

Trametinib, also known as GSK1120212, is a n orally bioavailable inhibitor of mitogen-activated protein kinase kinase (MEK MAPK/ERK kinase) with potential antineoplastic activity. Trametinib specifically binds to and inhibits MEK 1 and 2, resulting in an inhibition of growth factor-mediated cell signaling and cellular proliferation in various cancers. MEK 1 and 2, dual specificity threonine/tyrosine kinases often upregulated in various cancer cell types, play a key role in the activation of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth. On May 29, 2013, FDA approved T rametinib.

Product information

CAS Number: 871700-17-3

Molecular Weight: 615.39

Formula: C26H23FIN5O4

Synonym:

GSK-1120212

JTP74057

Mekinist

Chemical Name: N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]acetamide

Smiles: CN1C(NC2=CC=C(I)C=C2F)=C2C(=C(C)C1=O)N(C1=CC(=CC=C1)NC(C)=O)C(=O)N(C1CC1)C2=O

InChiKey: LIRYPHYGHXZJBZ-UHFFFAOYSA-N

InChi: InChI=1S/C26H23FIN5O4/c1-13-22-21(23(31(3)24(13)35)30-20-10-7-15(28)11-19(20)27)25(36)33(17-8-9-17)26(37)32(22)18-6-4-5-16(12-18)29-14(2)34/h4-7,10-12,17,30H,8-9H2,1-3H3,(H,29,34)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Trametinib (GSK1120212;JTP-74057) (0.1-100 nM) blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs). Trametinib (JTP-74057) inhibits the growth of 9 out of 10 human colorectal cancer cell lines, and they shows cell-cycle arrest at the G1 phase after drug tratment. The combination of GSK2118436 and Trametinib (GSK1120212) effectively inhibits cell growth, decreases ERK phosphorylation, decreases cyclin D1 protein, and increases p27(kip1) protein in the resistant clones.

In Vivo:

Adjuvant-induced arthritis (AIA) and type II collageninduced arthritis (CIA) development are suppressed almost completely by 0.1 mg/kg of Trametinib (GSK1120212; JTP-74057) or 10 mg/kg of HWA486. Trametinib (0.3 mg/kg, 1 mg/kg, p.o.) is effective in inhibiting the HT-29 xenograft growth in a nude mouse xenograft model.

References:

1. Kasuga A, Nakagawa K, Nagashima F, Shimizu T, Naruge D, Nishina S, Kitamura H, Kurata T, Takasu A, Fujisaka Y, Okamoto W, Nishimura Y, Mukaiyama A, Matsushita H, Furuse J. A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors. Invest New Drugs. 2015 Aug 12. [Epub ahead of print] PubMed PMID: 26259955.
2. Giurcaneanu C, Nitipir C, Popa LG, Forsea AM, Popescu I, Bumbacea RS. Evolution of Melanocytic Nevi under Vemurafenib, Followed by Combination Therapy with Dabrafenib and Trametinib for Metastatic Melanoma. Acta Dermatovenerol Croat. 2015 Jul;23(2):87-95. Review. PubMed PMID: 26228819.
3. Modak S, Asante-Korang A, Steinherz LJ, Grana N. Trametinib-induced Left Ventricular Dysfunction in a Child With Relapsed Neuroblastoma. J Pediatr Hematol Oncol. 2015 Aug;37(6):e381-3. doi: 10.1097/MPH.0000000000000364. PubMed PMID: 26181424.

Products are for research use only. Not for human use.