Tìm theo
Pasireotide
Các tên gọi khác (6 ) :
  • cyclo((4R)-4-(2-Aminoethylcarbamoyloxy)-L-prolyl-L-phenylglycyl-D-tryptophyl-L-lysyl-4-O-benzyl-L-tyrosyl-L- phenylalanyl-)
  • Pasireotida
  • Pasireotidum
  • SOM 230
  • SOM-230
  • SOM230
Thuốc Gốc
Small Molecule
CAS: 396091-73-9
ATC: H01CB05
CTHH: C58H66N10O9
PTK: 1047.2062
Pasireotide is a synthetic long-acting cyclic hexapeptide with somatostatin-like activity. It is marketed as a diaspartate salt called Signifor®, which is used in the treatment of Cushing's disease.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C58H66N10O9
Phân tử khối
1047.2062
Monoisotopic mass
1046.50142376
InChI
InChI=1S/C58H66N10O9/c59-27-13-12-22-46-52(69)64-47(30-38-23-25-42(26-24-38)76-36-39-16-6-2-7-17-39)53(70)66-49(31-37-14-4-1-5-15-37)57(74)68-35-43(77-58(75)61-29-28-60)33-50(68)55(72)67-51(40-18-8-3-9-19-40)56(73)65-48(54(71)63-46)32-41-34-62-45-21-11-10-20-44(41)45/h1-11,14-21,23-26,34,43,46-51,62H,12-13,22,27-33,35-36,59-60H2,(H,61,75)(H,63,71)(H,64,69)(H,65,73)(H,66,70)(H,67,72)/t43-,46+,47+,48-,49+,50+,51+/m1/s1
InChI Key
InChIKey=VMZMNAABQBOLAK-DBILLSOUSA-N
IUPAC Name
(3S,6R,9S,12S,15S,19R,20aS)-9-(4-aminobutyl)-15-benzyl-12-{[4-(benzyloxy)phenyl]methyl}-6-(1H-indol-3-ylmethyl)-1,4,7,10,13,16-hexaoxo-3-phenyl-icosahydropyrrolo[1,2-a]1,4,7,10,13,16-hexaazacyclooctadecan-19-yl N-(2-aminoethyl)carbamate
Traditional IUPAC Name
(3S,6R,9S,12S,15S,19R,20aS)-9-(4-aminobutyl)-15-benzyl-12-{[4-(benzyloxy)phenyl]methyl}-6-(1H-indol-3-ylmethyl)-1,4,7,10,13,16-hexaoxo-3-phenyl-tetradecahydropyrrolo[1,2-a]1,4,7,10,13,16-hexaazacyclooctadecan-19-yl N-(2-aminoethyl)carbamate
SMILES
NCCCC[C@@H]1NC(=O)[C@@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@@H]2C[C@H](CN2C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CC=C(OCC3=CC=CC=C3)C=C2)NC1=O)OC(=O)NCCN)C1=CC=CC=C1
Độ hòa tan
Soluble in water.
logP
2.68
logS
-5.7
pKa (strongest acidic)
9.09
pKa (Strongest Basic)
10.43
PSA
281.2 Å2
Refractivity
286.66 m3·mol-1
Polarizability
111.29 Å3
Rotatable Bond Count
18
H Bond Acceptor Count
10
H Bond Donor Count
9
Physiological Charge
2
Number of Rings
8
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Signifor® is an analogue of somatostatin that promotes reduced levels of cortisol secretion in Cushing's disease patients.
Cơ Chế Tác Dụng : Pasireotide is a synthetic long-acting cyclic hexapeptide with somatostatin-like activity. It is marketed as a diaspartate salt called Signifor®, which is used in the treatment of Cushing's disease. Pasireotide activates a broad spectrum of somatostatin receptors, exhbiting a much higher binding affinity for somatostatin receptors 1, 3, and 5 than octreotide in vitro, as well as a comparable binding affinity for somatostatin receptor 2. The binding and activation of the somatostatin receptors causes inhibition of ACTH secretion and results in reduced cortisol secretion in Cushing's disease patients. Also this agent is more potent than somatostatin in inhibiting the release of human growth hormone (HGH), glucagon, and insulin.
Dược Động Học :
▧ Absorption :
The peak plasma concentration of pasireotide occurs in 0.25-0.5 hours. After administration of single and multiple doses, there is dose-proportionoal increases in Cmax and AUC.
▧ Volume of Distribution :
Pasireotide is widely distributed and has a volume of distribution of >100L.
▧ Protein binding :
Plasma protein binding is 88%.
▧ Metabolism :
Metabolism is minimal.
▧ Route of Elimination :
Pasireotide is eliminated mostly by hepatic clearance (biliary excretion)(about 48%) with some minor renal clearance (about 7.63%).
▧ Half Life :
The half-life is 12 hours.
▧ Clearance :
The clearance in healthy patient is ~7.6 L/h and in Cushing’s disease patients is ~3.8 L/h.
Độc Tính : The most common toxic effects observed are hyperglycemia, cholelithiasis, diarrhea, nausea, headache, abdominal pain, fatigue, and diabetes mellitus.
Chỉ Định : For the treatment of Cushing’s disease, specifically for those patients whom pituitary surgery has not been curative or is not an option.
Tương Tác Thuốc :
  • Mifepristone Avoid combination with mifepristone and other moderate to high risk QTc prolonging agents. The combinaton may enhance the QTc-prolonging effect of these drugs.
Liều Lượng & Cách Dùng : Solution - Subcutaneous - 0.3 mg/mL (pasireotide diaspartate)
Solution - Subcutaneous - 0.6 mg/mL (pasireotide diaspartate)
Solution - Subcutaneous - 0.9 mg/mL (pasireotide diaspartate)
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : Novartis
    Sản phẩm biệt dược : Signifor
  • Công ty : Novartis
    Sản phẩm biệt dược : Signifor LAR
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06663
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D10147
Wikipedia
http://en.wikipedia.org/wiki/Pasireotide
RxList
http://www.rxlist.com/signifor-drug.htm
Drugs.com
http://www.drugs.com/signifor.html
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