Tìm theo
PX-12
Các tên gọi khác (1) :
  • 1-methylpropyl 2-imidazolyl disulfide
Thuốc Gốc
Small Molecule
CTHH: C7H12N2S2
PTK: 188.314
PX-12 (1-methylpropyl 2-imidazolyl disulfide) is a small-molecule inhibitor of Trx-1 (thioredoxin-1), stimulates apoptosis, down-regulates HIF-1α and vascular endothelial growth factor (VEGF) and inhibits tumor growth in animal models. Since high levels of Trx-1 have been associated with colorectal, gastric and lung cancers, PX-12 is indicated as a potential cancer treatment in combination with chemotherapy for patients with advanced metastatic cancer. Initial trials correlated doses of Px-12 with increased patient survival.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C7H12N2S2
Phân tử khối
188.314
Monoisotopic mass
188.044189774
InChI
InChI=1S/C7H12N2S2/c1-3-6(2)10-11-7-8-4-5-9-7/h4-6H,3H2,1-2H3,(H,8,9)
InChI Key
InChIKey=BPBPYQWMFCTCNG-UHFFFAOYSA-N
IUPAC Name
2-(butan-2-yldisulfanyl)-1H-imidazole
Traditional IUPAC Name
2-(sec-butyldisulfanyl)-1H-imidazole
SMILES
CCC(C)SSC1=NC=CN1
Độ hòa tan
7.83e-01 g/l
logP
2.77
logS
-2.4
pKa (strongest acidic)
10.93
pKa (Strongest Basic)
4.81
PSA
28.68 Å2
Refractivity
50.87 m3·mol-1
Polarizability
19.94 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
1
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
1
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : PX-12 is a small molecule irreversible inhibitor of the redox protein thioredoxin. Thioredoxin is involved in the first unique step in DNA synthesis. Thioredoxin also provides control over a number of transcription factors affecting cell proliferation and death through the mechanism of redox regulation Trx regulates cell growth through the following steps: 1) Trx is reduced into its active state, Trx (red) by the enzyme thioredoxin reductase. 2) Trx enters the nucleus to regulate transcription factor activity (factors which affect DNA replication). 3) Trx is excreted out of cell where it works with other growth factors (GF) to stimulate cell growth. It has been shown that many cancer cells secrete thioredoxin; increased levels of thioredoxin protein have been reported in a wide range of human cancers including hepatoma, lung, squamous cervical carcinoma, primary gastric cancers, and colorectal carcinomas;thioredoxin stimulates the growth of a wide variety of human leukemia and solid tumor cell lines; thioredoxin, when it is over-produced, transforms normal cells into cancer cells; thioredoxin is a potent inhibitor of apoptosis and provides a survival as well as a growth advantage to tumors; elevated tumor thioredoxin levels have been associated with decreased patient survival in colon cancer and NSCLC; and elevated thioredoxin levels cause a decrease in sensitivity of cells to cancer drugs such as doxorubicin (14 fold), vincristine (8 fold), cisplatin (5 fold), and cytosine arabinoside (13 fold). Therefore PX-12, by limiting the over-expression of thioredoxin in human tumors, could reduce resistance to chemotherapy.
Cơ Chế Tác Dụng : PX-12 (1-methylpropyl 2-imidazolyl disulfide) is a small-molecule inhibitor of Trx-1 (thioredoxin-1), stimulates apoptosis, down-regulates HIF-1α and vascular endothelial growth factor (VEGF) and inhibits tumor growth in animal models. Since high levels of Trx-1 have been associated with colorectal, gastric and lung cancers, PX-12 is indicated as a potential cancer treatment in combination with chemotherapy for patients with advanced metastatic cancer. Initial trials correlated doses of Px-12 with increased patient survival. PX-12 irreversibly inhibits the redox protein thioredoxin, which has been associated with cancer and tumor growth.
Dược Động Học :
▧ Absorption :
the optimum PD dose was identified as 96 mg/m2 as a 3-hr infusion
Độc Tính : Doses of PX-12 up to 226 mg/m2 were shown to be well tolerated and had minimal toxicity
Chỉ Định : Investigated for use/treatment in cancer/tumors (unspecified), gastric cancer, and pancreatic cancer.
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB05448
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=219104
ChemSpider
http://www.chemspider.com/Chemical-Structure.189920.html
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