Tìm theo
Trametinib
Các tên gọi khác (4 ) :
  • GSK 1120212
  • JTP 74057
  • Trametinib Dimethyl Sulfoxide
  • Trametinibum
Thuốc Gốc
Small Molecule
CAS: 871700-17-3
CTHH: C26H23FIN5O4
PTK: 615.3948
Trametinib dimethyl sulfoxide is a kinase inhibitor. Each 1-mg tablet contains 1.127 mg trametinib dimethyl sulfoxide equivalent to 1 mg of trametinib non-solvated parent. FDA approved on May 29, 2013.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C26H23FIN5O4
Phân tử khối
615.3948
Monoisotopic mass
615.077875874
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)
InChI Key
InChIKey=LIRYPHYGHXZJBZ-UHFFFAOYSA-N
IUPAC Name
N-(3-{3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-1H,2H,3H,4H,6H,7H-pyrido[4,3-d]pyrimidin-1-yl}phenyl)acetamide
Traditional IUPAC Name
N-(3-{3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl}phenyl)acetamide
SMILES
CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1
Độ hòa tan
3.07e-02 g/l
logP
3.18
logS
-4.3
pKa (strongest acidic)
12.6
pKa (Strongest Basic)
-3.7
PSA
102.06 Å2
Refractivity
156.38 m3·mol-1
Polarizability
55.43 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
5
Bioavailability
1
Dược Lực Học : When 1 mg and 2 mg trametinib is given to patients with BRAF V600 mutation-positive melanoma, an inhibition of phosphorylated ERK and Ki67, and an increase in p27 was observed. These changes indicate that trametinib caused a decrease in cell proliferation and an increase in apoptosis, respectively.
Cơ Chế Tác Dụng : Trametinib dimethyl sulfoxide is a kinase inhibitor. Each 1-mg tablet contains 1.127 mg trametinib dimethyl sulfoxide equivalent to 1 mg of trametinib non-solvated parent. FDA approved on May 29, 2013. Trametinib is a reversible, allosteric inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activation and of MEK1 and MEK2 kinase activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation. Trametinib helps with melanoma with the BRAF V600E or V600K as the mutation results in the constitutive activation of the BRAF pathway which includes MEK1 and MEK2.
Dược Động Học :
▧ Absorption :
Trametinib is rapidly absorbed. When an oral administration of trametinib was given to patients with BRAF V600 mutation-positive melanoma, peak plasma concentration occurred 1.5 hours post-dose (Tmax). A single 2 mg oral dose has a bioavailability of 72%. When a dose of 2mg/day is given, the peak plasma concentration (Cmax) is 22.2 ng/mL.
▧ Volume of Distribution :
Apparent volume of distribution (Vd/F) = 214 L
▧ Protein binding :
97.4% bound to human plasma proteins.
▧ Metabolism :
Trametinib is metabolized predominantly via deacetylation alone or with mono-oxygenation or in combination with glucuronidation biotransformation pathways in vitro. Deacetylation is likely mediated by hydrolytic enzymes, such as carboxyl-esterases or amidases. The cytochrome P450 enzyme system is not involved with the metabolism of trametinib. The predominant circulating component in the plasma is the parent compound.
▧ Route of Elimination :
80% of the dose is excreted in the feces. <20% of the dose is excreted in the urine with <0.1% of the excreted dose in the form of the parent compound.
▧ Half Life :
Elimination half-life = 3.9-4.8 days.
▧ Clearance :
Apparent clearance = 4.9 L/h.
Độc Tính : Most common adverse reactions (≥20%) for trametinib include rash, diarrhea, and lymphedema.
Chỉ Định : Trametinib is indicated for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test.
Liều Lượng & Cách Dùng : Tablet - Oral - 0.5 mg, 1 mg, 2 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08911
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D10175
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0173-0848-13
Wikipedia
http://en.wikipedia.org/wiki/Trametinib
RxList
http://www.rxlist.com/mekinist-drug.htm
Drugs.com
http://www.drugs.com/mekinist.html
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