Trametinib

Trametinib
Clinical data

Trade names	Mekinist
Pregnancy category	US: D (Evidence of risk)
ATC code	L01XE25 (WHO)
Legal status
Legal status	US: ℞-only
Identifiers
IUPAC name 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
Synonyms	GSK1120212
CAS Number	871700-17-3
PubChem (CID)	11707110
ChemSpider	9881833
UNII	33E86K87QN^Y
ChEBI	CHEBI:75998
ChEMBL	CHEMBL2103875
ECHA InfoCard	100.158.135
Chemical and physical data
Formula	C₂₆H₂₃FIN₅O₄
Molar mass	615.39 g/mol
3D model (Jmol)	Interactive image
SMILES Ic1ccc(c(F)c1)N\C3=C\2/C(=O)N(C(=O)N(C/2=C(\C(=O)N3C)C)c4cccc(NC(=O)C)c4)C5CC5
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) Key:LIRYPHYGHXZJBZ-UHFFFAOYSA-N

Trametinib (trade name Mekinist) is a cancer drug. It is a MEK inhibitor drug with anti-cancer activity.^[1]

It inhibits MEK1 and MEK2.^[1]

Trametinib had good results for metastatic melanoma carrying the BRAF V600E mutation in a phase III clinical trial. In this mutation, the amino acid valine (V) at position 600 within the BRAF gene has become replaced by glutamic acid (E) making the mutant BRAF gene constitutively active.^[2]

In May 2013, trametinib was approved as a single-agent by the Food and Drug Administration for the treatment of patients with V600E mutated metastatic melanoma.^[3] Clinical trial data demonstrated that resistance to single-agent trametinib often occurs within 6 to 7 months.^[4] To overcome this, trametinib was combined with the BRAF inhibitor dabrafenib.^[4] As a result of this research, on January 8, 2014, the FDA approved the combination of dabrafenib and trametinib for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma.^[5]

References

1 2 Trametinib, NCI Drug Dictionary
↑ METRIC phase III study: Efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients (pts) with BRAFV600E/K mutant advanced or metastatic melanoma (MM).
↑ "GSK melanoma drugs add to tally of U.S. drug approvals". Reuters. May 30, 2013.
1 2 "Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations". 367 (18). New England Journal of Medicine. November 1, 2012: 1694–703. doi:10.1056/NEJMoa1210093. PMC 3549295. PMID 23020132.
↑ "Dabrafenib/Trametinib Combination Approved for Advanced Melanoma". OncLive. January 9, 2014.

Targeted therapy / extracellular chemotherapeutic agents/antineoplastic agents (L01)

CI monoclonal antibodies ("-mab")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Cetuximab Panitumumab) HER2/neu (Trastuzumab Trastuzumab emtansine)

Others for solid tumors	EpCAM (Catumaxomab Edrecolomab) VEGF-A (Bevacizumab)

Leukemia/lymphoma	lymphoid: CD20 (Ibritumomab Ofatumumab Rituximab Tositumomab), CD30 (Brentuximab), CD52 (Alemtuzumab) myeloid: CD33 (Gemtuzumab)

Tyrosine-kinase inhibitors ("-nib")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Erlotinib Gefitinib Olmutinib Osimertinib Rociletinib Vandetanib) HER1/EGFR and HER2/neu Afatinib Lapatinib Neratinib RTK class III: C-kit and PDGFR (Axitinib Masitinib Pazopanib Sunitinib Sorafenib Toceranib) FLT3 (Lestaurtinib) VEGFR Axitinib Cediranib Lenvatinib Nintedanib Pazopanib Regorafenib Semaxanib Sorafenib Sunitinib Tivozanib Toceranib Vandetanib RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK). c-MET inhibitor: Cabozantinib (also VEGFR2).

Non-receptor	bcr-abl Imatinib Dasatinib Nilotinib Ponatinib Radotinib Src (Bosutinib) Janus kinase Lestaurtinib Momelotinib Ruxolitinib Pacritinib MAP2K Cobimetinib Selumetinib Trametinib Binimetinib EML4-ALK Alectinib Ceritinib Crizotinib Bruton's (Ibrutinib)

Other

fusion protein against VEGF (Aflibercept)
proapoptotic peptide against ANXA2 and prohibitin (Adipotide)
exotoxin against IL-2 (Denileukin diftitox)
mTOR inhibitors
- Everolimus
- Temsirolimus
hedgehog inhibitors
- Sonidegib
- Vismodegib
CDK inhibitor (Palbociclib)

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