Tìm theo
Trabectedin
Các tên gọi khác (3) :
  • Ecteinascidin 743
  • SID144206315
  • SID144206787
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 114899-77-3
ATC: L01CX01
CTHH: C39H43N3O11S
PTK: 761.837
Trabectedin, also referred as ET-743 during its development, is a marine derived antitumoral agent discovered in the Carribean tunicate _Ecteinascidia turbinata_ and now produced synthetically. Trabectedin has a unique mechanism of action. It binds to the minor groove of DNA interfering with cell division and genetic transcription processes and DNA repair machinery.It is approved for use in Europe, Russia and South Korea for the treatment of advanced soft tissue sarcoma. It is also undergoing clinical trials for the treatment of breast, prostate, and paediatric sarcomas. The European Commission and the U.S. Food and Drug Administration (FDA) have granted orphan drug status to trabectedin for soft tissue sarcomas and ovarian cancer.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C39H43N3O11S
Phân tử khối
761.837
Monoisotopic mass
761.261829923
InChI
InChI=1S/C39H43N3O11S/c1-16-9-20-10-22-37(46)42-23-13-50-38(47)39(21-12-25(48-5)24(44)11-19(21)7-8-40-39)14-54-36(30(42)29(41(22)4)26(20)31(45)32(16)49-6)28-27(23)35-34(51-15-52-35)17(2)33(28)53-18(3)43/h9,11-12,22-23,29-30,36-37,40,44-46H,7-8,10,13-15H2,1-6H3/t22-,23-,29+,30+,36+,37-,39+/m0/s1
InChI Key
InChIKey=PKVRCIRHQMSYJX-AIFWHQITSA-N
IUPAC Name
(1R,2R,3R,11S,12S,14R,26R)-5,6',12-trihydroxy-6,7'-dimethoxy-7,21,30-trimethyl-27-oxo-3',4'-dihydro-2'H-17,19,28-trioxa-24-thia-13,30-diazaspiro[heptacyclo[12.9.6.1³,¹¹.0²,¹³.0⁴,⁹.0¹⁵,²³.0¹⁶,²⁰]triacontane-26,1'-isoquinoline]-4(9),5,7,15,20,22-hexaen-22-yl acetate
Traditional IUPAC Name
yondelis
SMILES
[H][C@@]12[C@@H]3SC[C@]4(NCCC5=C4C=C(OC)C(O)=C5)C(=O)OC[C@H](N1[C@@H](O)[C@@H]1CC4=CC(C)=C(OC)C(O)=C4[C@H]2N1C)C1=C2OCOC2=C(C)C(OC(C)=O)=C31
Độ hòa tan
3.28e-01 g/l
logP
3.99
logS
-3.4
pKa (strongest acidic)
9.27
pKa (Strongest Basic)
7.66
PSA
168.72 Å2
Refractivity
196.92 m3·mol-1
Polarizability
77.72 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
12
H Bond Donor Count
4
Physiological Charge
1
Number of Rings
9
Bioavailability
0
Dược Lực Học : Two of the rings in the drug's structure allows it to covalently bind to the minor groove of DNA. The third ring protrudes from the DNA which lets it interact with nearby nuclear proteins. This has the additive effect of blocking cell division at the G2 phase.
Cơ Chế Tác Dụng : Trabectedin, also referred as ET-743 during its development, is a marine derived antitumoral agent discovered in the Carribean tunicate _Ecteinascidia turbinata_ and now produced synthetically. Trabectedin has a unique mechanism of action. It binds to the minor groove of DNA interfering with cell division and genetic transcription processes and DNA repair machinery.It is approved for use in Europe, Russia and South Korea for the treatment of advanced soft tissue sarcoma. It is also undergoing clinical trials for the treatment of breast, prostate, and paediatric sarcomas. The European Commission and the U.S. Food and Drug Administration (FDA) have granted orphan drug status to trabectedin for soft tissue sarcomas and ovarian cancer. Trabectedin interacts with the minor groove of DNA and alkylates guanine at the N2 position, which bends towards the major groove. In this manner, it is thought that the drug affects various transcription factors involved in cell proliferation, particularly via the transcription-coupled nucleotide excision repair system. Trabectedin blocks the cell cycle at the G2 phase, while cells at the G1 phase are most sensitive to the drug. It also inhibits overexpression of the multidrug resistance-1 gene (MDR-1) coding for the P-glycoprotein that is a major factor responsible for cells developing resistance to cancer drugs. The agent is also thought to interfere with the nucleotide excision repair pathways of cancer cells, suggesting that it could be effective in the treatment of many cancer types including melanoma and sarcoma, as well as lung, breast, ovarian, endometrial and prostate cancers; clinical evaluations are underway in these indications.
Dược Động Học :
▧ Absorption :
Administered intravenously.
▧ Protein binding :
94 to 98%
▧ Half Life :
33-50 hours
Chỉ Định : Indicated for treatment of advanced soft tissue sarcoma in patients refractory to or unsuitable to receive anthracycline or ifosfamide chemotherapy in Europe, Russia and South Korea. Approved for orphan drug status by the U.S. FDA for treatment of soft tissue sarcomas and ovarian cancer. Investigated for use/treatment in cancer/tumors (unspecified), gastric cancer, ovarian cancer, pediatric indications, sarcoma, and solid tumors.
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Yondelis
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB05109
PharmGKB
http://www.pharmgkb.org/drug/PA165958349
Wikipedia
http://en.wikipedia.org/wiki/Trabectedin
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