Tìm theo
Afatinib
Các tên gọi khác (2) :
  • Afatinibum
  • BIBW 2992
Thuốc Gốc
Small Molecule
CAS: 850140-72-6
ATC: L01XE13
CTHH: C24H25ClFN5O3
PTK: 485.938
Afatinib is a tyrosine kinase inhibitor which is a 4-anilinoquinazoline. It is prepared has the dimaleate salt. FDA approved on July 12, 2013.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C24H25ClFN5O3
Phân tử khối
485.938
Monoisotopic mass
485.162995603
InChI
InChI=1S/C24H25ClFN5O3/c1-31(2)8-3-4-23(32)30-21-11-17-20(12-22(21)34-16-7-9-33-13-16)27-14-28-24(17)29-15-5-6-19(26)18(25)10-15/h3-6,10-12,14,16H,7-9,13H2,1-2H3,(H,30,32)(H,27,28,29)/b4-3+/t16-/m0/s1
InChI Key
InChIKey=ULXXDDBFHOBEHA-CWDCEQMOSA-N
IUPAC Name
(2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[(3S)-oxolan-3-yloxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide
Traditional IUPAC Name
afatinib
SMILES
CN(C)C\C=C\C(=O)NC1=C(O[C@H]2CCOC2)C=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1
Độ hòa tan
1.28e-02 g/l
logP
3.76
logS
-4.6
pKa (strongest acidic)
12.49
pKa (Strongest Basic)
8.81
PSA
88.61 Å2
Refractivity
131.38 m3·mol-1
Polarizability
50.07 Å3
Rotatable Bond Count
8
H Bond Acceptor Count
7
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
4
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Dược Lực Học : Afatinib did not effect the QTc interval.
Cơ Chế Tác Dụng : Afatinib is a tyrosine kinase inhibitor which is a 4-anilinoquinazoline. It is prepared has the dimaleate salt. FDA approved on July 12, 2013. Afatinib is an irreversible kinase inhibitor and binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) to inhibit tyrosine kinase autophosphorylation. This results in a downregulation of ErbB signalling and subsequent inhibition of proliferation of cell lines expressing wild-type EGFR, selected EGFR exon 19 deletion mutations, or exon 21 L858R mutations. It also inhibited in vitro proliferation of cell lines overexpressing HER2. Overall, tumour growth was inhibited.
Dược Động Học :
▧ Absorption :
Following oral administration, time to peak plasma concentration (Tmax) is 2 to 5 hours. The geometric mean relative bioavailability of 20 mg tablets was 92% as compared to an oral solution. Food decreases Cmax and AUC relative to the fasted state.
▧ Protein binding :
95% bound to human plasma protein.
▧ Metabolism :
Enzymatic metabolism of afatinib is minimal. Covalent adducts to proteins are the major circulating metabolites.
▧ Route of Elimination :
Excretion of afatinib is primarily via the feces (85%), with 4% recovered in the urine following a single oral dose of afatinib solution. The parent compound accounted for 88% of the recovered dose.
▧ Half Life :
Cancer patients, repeat dosing = 37 hours
Độc Tính : Most common adverse reactions (≥20%) are diarrhea, rash/dermatitis, acneiform, stomatitis, paronychia, dry skin, decreased appetite, pruritus.
Chỉ Định : Afatinib is a kinase inhibitor indicated for the first-line treatment of patient with metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.
Liều Lượng & Cách Dùng : Tablet - Oral - 20 mg, 30 mg, 40 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08916
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09724
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0597-0138-30
Wikipedia
http://en.wikipedia.org/wiki/Afatinib
Drugs.com
http://www.drugs.com/gilotrif.html
... loading
... loading