Repositioning Candidate Details
| Candidate ID: | R0802 |
| Source ID: | DB05448 |
| Source Type: | investigational |
| Compound Type: | small molecule |
| Compound Name: | PX-12 |
| Synonyms: | 1-Methylpropyl-2-imidazolyl disulfide |
| Molecular Formula: | C7H12N2S2 |
| SMILES: | CCC(C)SSC1=NC=CN1 |
| Structure: |
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| DrugBank Description: | 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. |
| CAS Number: | 141400-58-0 |
| Molecular Weight: | 188.314 |
| DrugBank Indication: | Investigated for use/treatment in cancer/tumors (unspecified), gastric cancer, and pancreatic cancer. |
| DrugBank Pharmacology: | 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. |
| DrugBank MoA: | PX-12 irreversibly inhibits the redox protein thioredoxin, which has been associated with cancer and tumor growth. |
| Targets: | Thioredoxin reductase 1, cytoplasmic |
| Inclusion Criteria: | Therapeutic strategy associated |
