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Trametinib

Abstract Biological activity In vitro In vivo Features References
Trametinib
Trametinib structure
CAS No.
871700-17-3
Chemical Name:
Trametinib
Synonyms
TraMetinib;CB32514557;GSK-1120212;TraMetinib API;QuMei iMatinib;Trametinib, >=98%;Trametinib Impurity;Trametinib free base;Mekinist trametinib;TraMetinib/GSK1120212
CBNumber:
CB32514557
Molecular Formula:
C26H23FIN5O4
Formula Weight:
615.3947932
MOL File:
871700-17-3.mol

Trametinib Properties

Melting point:
300-301 °C
Density 
1.74
form 
White solid.
pka
14.76±0.70(Predicted)
SAFETY
  • Risk and Safety Statements
Safety Statements  24/25
HS Code  29339900

Trametinib price More Price(4)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 16292 Trametinib ≥95% 871700-17-3 25mg $55 2018-11-19 Buy
Cayman Chemical 16292 Trametinib ≥95% 871700-17-3 50mg $94 2018-11-13 Buy
Cayman Chemical 16292 Trametinib ≥95% 871700-17-3 100mg $110 2018-11-19 Buy
Cayman Chemical 16292 Trametinib ≥95% 871700-17-3 250mg $248 2018-11-19 Buy

Trametinib Chemical Properties,Uses,Production

Abstract

Trametinib (trade name Mekinist) is a cancer drug. It is a MEK inhibitor drug with anti-cancer activity.
Trametinib(Mekinist) is a reversible, highly selective, allosteric inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activation and kinase activity. MEK proteins are components of the extracellular signal-related kinase (ERK) pathway. In melanoma and other cancers, this pathway is often activated by mutated forms of BRAF which activates MEK. Trametinib inhibits activation of MEK by BRAF and inhibits MEK kinase activity. Trametinib inhibits growth of BRAF V600 mutant melanoma cell lines and demonstrates anti-tumor effects in BRAF V600 mutant melanoma animal models.
Mekinist is indicated as monotherapy or in combination with Tafinlar (dabrafenib) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

Biological activity

Trametinib (GSK1120212) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2.

In vitro

For the different subtypes of Raf and MEK, with IC50 ranging from 0.92 nM to 3.4 nM,GSK1120212 inhibits the phosphorylation of MBP. GSK1120212 demonstrates no inhibition of the kinase activities of c-Raf, B-Raf, ERK1 and ERK2. In addition, GSK1120212 does not show drastic inhibitory activity against the other 98 kinases. GSK1120212 displays potent inhibitory activity against human colorectal cancer cell lines. HT-29 and COLO205 cells, which are known to have a constitutively active B-Raf mutant, are most sensitive to GSK1120212 with IC50 0.48 nM and 0.52 nM, respectively. The cell lines bearing a K-Ras mutation show a wide range of sensitivity to GSK1120212 with IC50 of 2.2-174 nM. In contrast, COLO320 DM cells, bearing the wild-type gene in both B-Raf and K-Ras, are found to be resistant to GSK1120212 even at 10 μM. GSK1120212 treatment for 24 hours induces cell-cycle arrest at the G1 phase in all sensitive cell lines. Consistently, GSK1120212 treatment leads to upregulation of p15INK4b and/or p27KIP1 in most of the colorectal cancer cell lines. GSK1120212 induces apoptosis both in HT-29 and COLO205 cells, but that COLO205 cells are more sensitive to GSK1120212 than HT-29 cells in terms of apoptosis induction.GSK1120212 blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs).

In vivo

Oral administration of GSK1120212 at 0.3 mg/kg or 1 mg/kg once daily for 14 days is effective in inhibiting the HT-29 xenograft growth, and 1 mg/kg of GSK1120212 can completely block the tumor increase. The phosphorylation of ERK1/2 is completely inhibited in the established tumor tissues by single oral dose of 1 mg/kg GSK1120212, and both p15INK4b and p27KIP1 protein levels are upregulated after 14 days of treatment with GSK1120212. In the COLO205 xenograft model, tumor regression is observed even at a dose of 0.3 mg/kg. At a dose of 1 mg/kg, a complete regression is obtained in 4 out of 6 mice in which the tumor degenerates to the point that tumor volume is not measurable. Administration of GSK1120212 at 0.1 mg/kg almost completely suppresses adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) in Lewis rats or DBA1/J mice, respectively.

Features

More potent than PD0325901 or AZD6244.

References

https://en.wikipedia.org/wiki/Trametinib
https://www.novartisoncology.com/news/product-portfolio/mekinist

Uses

Used in the systematic treatment of advanced cutaneous melanoma. An EGFR kinase inhibitor.

Uses

antiprotozoal

Definition

ChEBI: A pyridopyrimidine that is used (as its dimethyl sulfoxide addition compound) for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, and who have not received prior BRAF inhibitor treatment.

Indications

MEK, also known as MAPK, is a dual specificity threonine/tyrosine kinase that is a key node in the Raf–Ras–MEK signaling pathway. Small-molecule MEK inhibitors represent the largest group of type III allosteric inhibitors that do not bind to the ATP binding pocket. As of December 2016, besides the FDA-approved MEK1/2 inhibitors trametinib (Mekinist(R), GlaxoSmithKline) and cobimetinib (Cotellic(R), Roche), over 10 MEK inhibitors are currently in clinical trials. Trametinib was approved by FDA in 2013 for the treatment of patients with either B-Raf V600E or V600K mutated metastatic melanoma. Considering the fact that MEK and Raf are different kinases along the same pathway of Ras–Raf–MEK/ERK signaling cascade, combination strategies using both MEK and B-Raf inhibitors were utilized to overcome the observed progression using single-agent trametinib, which usually occurs within 7months. FDA approved the combination of trametinib and dabrafenib for the treatment of B-Raf V600E/K mutated metastatic melanoma in January 2014 and the combination of cobimetinib and vemurafenib for the same type of indication. Although significant improvement in progression-free survival was observed using MEK/B-Raf combination strategy, the incidence of some common adverse effects, such as vomiting, diarrhea, nausea, rash, and pyrexia, also increased.

Trametinib Preparation Products And Raw materials

Raw materials

Preparation Products


Trametinib Suppliers

Global( 167)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Henan DaKen Chemical CO.,LTD.
+86-371-55531817
info@dakenchem.com CHINA 21671 58
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 20672 55
Nanjing ChemLin Chemical Industry Co., Ltd.
025-83697070;product@chemlin.com.cn
product@chemlin.com.cn CHINA 3015 60
Nanjing Finetech Chemical Co., Ltd.
025-85710122 17714198479
025-85710122 sales@fine-chemtech.com CHINA 892 55
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 24191 60
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 30001 58
Biochempartner
0086-13720134139
candy@biochempartner.com CHINA 969 58
Chemwill Asia Co.,Ltd.
86-21-51086038
86-21-51861608 chemwill_asia@126.com;sales@chemwill.com;chemwill@hotmail.com;chemwill@gmail.com CHINA 23980 58
HubeiwidelychemicaltechnologyCo.,Ltd
18627774460
faith@widelychemical.com CHINA 700 58
Hubei xin bonus chemical co. LTD
86-13657291602
027-59338440 sales@guangaobio.com CHINA 23049 58

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View Lastest Price from Trametinib manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2019-10-29 Trametinib
871700-17-3
US $1.00 / Kg/Drum 25Kg/Drum 98% HPLC 1ton HubeiwidelychemicaltechnologyCo.,Ltd
2018-12-24 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
871700-17-3
US $2.00 / kg 1kg 99% 100kg career henan chemical co

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