Tìm theo
Thalidomide
Các tên gọi khác (26 ) :
  • (+-)-N-(2,6-dioxo-3-Piperidyl)phthalimide
  • (+-)-Thalidomide
  • (±)-N-(2,6-dioxo-3-piperidyl)phthalimide
  • (±)-thalidomide
  • 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindoline
  • 2,6-dioxo-3-phthalimidopiperidine
  • 3-Phthalimidoglutarimide
  • alpha-(N-Phthalimido)glutarimide
  • alpha-N-Phthalylglutaramide
  • alpha-Phthalimidoglutarimide
  • Distaval
  • K-17
  • N-(2,6-dioxo-3-piperidyl)phthalimide
  • N-Phthaloylglutamimide
  • N-Phthalyl-glutaminsaeure-imid
  • N-Phthalylglutamic acid imide
  • Pro-ban M
  • Sedalis
  • Softenon
  • Talidomida
  • Talimol
  • Thalidomide
  • Thalidomidum
  • α-(N-phthalimido)glutarimide
  • α-N-phthalylglutaramide
  • α-phthalimidoglutarimide
Thuốc giảm miễn dịch
Thuốc Gốc
Small Molecule
CAS: 50-35-1
ATC: L04AX02
ĐG : Celgene , http://www.celgene.com
CTHH: C13H10N2O4
PTK: 258.2295
A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor-alpha from monocytes, and modulates other cytokine action. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C13H10N2O4
Phân tử khối
258.2295
Monoisotopic mass
258.064056818
InChI
InChI=1S/C13H10N2O4/c16-10-6-5-9(11(17)14-10)15-12(18)7-3-1-2-4-8(7)13(15)19/h1-4,9H,5-6H2,(H,14,16,17)
InChI Key
InChIKey=UEJJHQNACJXSKW-UHFFFAOYSA-N
IUPAC Name
2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione
Traditional IUPAC Name
thalidomide
SMILES
O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC=C12
Độ tan chảy
270 °C
Độ hòa tan
545 mg/L (at 25 °C)
logP
0.33
logS
-2
pKa (strongest acidic)
11.59
pKa (Strongest Basic)
-6.4
PSA
83.55 Å2
Refractivity
64.32 m3·mol-1
Polarizability
24.42 Å3
Rotatable Bond Count
1
H Bond Acceptor Count
4
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Thalidomide is an immunomodulatory agent with a spectrum of activity that is not fully characterized. Thalidomide is racemic — it contains both left and right handed isomers in equal amounts: one enantiomer is effective against morning sickness, and the other is teratogenic. The enantiomers are converted to each other in vivo. That is, if a human is given D-thalidomide or L-thalidomide, both isomers can be found in the serum. Hence, administering only one enantiomer will not prevent the teratogenic effect in humans.
Cơ Chế Tác Dụng : A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor-alpha from monocytes, and modulates other cytokine action. [PubChem] In patients with erythema nodosum leprosum (ENL) the mechanism of action is not fully understood. Available data from in vitro studies and preliminary clinical trials suggest that the immunologic effects of this compound can vary substantially under different conditions, but may be related to suppression of excessive tumor necrosis factor-alpha (TNF-a) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration. For example, administration of thalidomide has been reported to decrease circulating levels of TNF-a in patients with ENL, however, it has also been shown to increase plasma TNF-a levels in HIV-seropositive patients. As a cancer treatment, the drug may act as a VEGF inhibitor.
Dược Động Học :
▧ Absorption :
The absolute bioavailability has not yet been characterized in human subjects due to its poor aqueous solubility. In studies of both healthy volunteers and subjects with Hansen’s disease, the mean time to peak plasma concentrations (Tmax) ranged from 2.9 to 5.7 hours indicating that thalidomide is slowly absorbed from the gastrointestinal tract.
▧ Protein binding :
55% and 66% for the (+)R and (−)S enantiomers, respectively.
▧ Metabolism :
Thalidomide itself does not appear to be hepatically metabolized to any large extent, but appears to undergo non-enzymatic hydrolysis in plasma to multiple metabolites. Thalidomide may be metabolized hepatically by enzymes of the cytochrome P450 enzyme system. The end product of metabolism, phthalic acid, is excreted as a glycine conjugate.
▧ Route of Elimination :
Thalidomide itself has less than 0.7% of the dose excreted in the urine as unchanged drug.
▧ Half Life :
The mean half-life of elimination ranges from approximately 5 to 7 hours following a single dose and is not altered upon multiple dosing.
Độc Tính : The R-configuration and the S-configuration are more toxic individually than the racemic mixture. The LD50 could not be established in mice for racemic thalidomide, whereas LD50 values for the R and S configurations are reported to be 0.4 to 0.7 g/kg and 0.5 to 1.5 g/kg, respectively.
Chỉ Định : For the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Also for use as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence.
Tương Tác Thuốc :
  • Abatacept Thalidomide may increase the adverse effects of Abatacept. Increased risk of serious infection. Concomitant therapy should be avoided.
  • Amikacin Thalidomide increases the renal toxicity of the aminoglycoside
  • Anakinra Thalidomide may increase the adverse effects of Anakinra. Increased risk of serious infection. Concomitant therapy should be avoided.
  • Dexamethasone Increased risk of dermatologic adverse effects and venous thromboembolic events (VTE). Consider VTE prophylaxis during concomitant therapy and monitor for adverse dematologic effects.
  • Gentamicin Thalidomide increases the renal toxicity of the aminoglycoside
  • Natalizumab Thalidomide may increase the adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.
  • Netilmicin Thalidomide increases the renal toxicity of the aminoglycoside
  • Rilonacept Thalidomide may increase the adverse effects of Rilonacept. Increased risk of serious infection. Concomitant therapy should be avoided.
  • Tobramycin Thalidomide increases the renal toxicity of the aminoglycoside
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Triprolidine The CNS depressants, Triprolidine and Thalidomide, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Liều Lượng & Cách Dùng : Capsule - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Contergan
  • Công ty :
    Sản phẩm biệt dược : Distaval
  • Công ty :
    Sản phẩm biệt dược : K-17
  • Công ty :
    Sản phẩm biệt dược : Sedalis
  • Công ty :
    Sản phẩm biệt dược : Softenon
  • Công ty :
    Sản phẩm biệt dược : Talimol
  • Công ty :
    Sản phẩm biệt dược : Thaled
  • Công ty :
    Sản phẩm biệt dược : Thalomid
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01041
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5426
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505665
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07910
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00754
ChemSpider
http://www.chemspider.com/Chemical-Structure.5233.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50070114
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/59572-205-14
PharmGKB
http://www.pharmgkb.org/drug/PA451644
Wikipedia
http://en.wikipedia.org/wiki/Thalidomide
RxList
http://www.rxlist.com/cgi/generic2/thalidom.htm
Drugs.com
http://www.drugs.com/cdi/thalidomide.html
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