Details
Stereochemistry | RACEMIC |
Molecular Formula | C7H12N2S2 |
Molecular Weight | 188.314 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCC(C)SSC1=NC=CN1
InChI
InChIKey=BPBPYQWMFCTCNG-UHFFFAOYSA-N
InChI=1S/C7H12N2S2/c1-3-6(2)10-11-7-8-4-5-9-7/h4-6H,3H2,1-2H3,(H,8,9)
DescriptionSources: https://www.drugbank.ca/drugs/DB05448Curator's Comment: The description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT00417287 | https://www.ncbi.nlm.nih.gov/pubmed/23327656 | https://clinicaltrials.gov/ct2/show/NCT00736372 | https://www.ncbi.nlm.nih.gov/pubmed/24172913
Sources: https://www.drugbank.ca/drugs/DB05448
Curator's Comment: The description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT00417287 | https://www.ncbi.nlm.nih.gov/pubmed/23327656 | https://clinicaltrials.gov/ct2/show/NCT00736372 | https://www.ncbi.nlm.nih.gov/pubmed/24172913
DB05448 (PX-12, 1-methyl propyl 2-imidazolyl disulfide) is a small molecule irreversible inhibitor of the redox protein thioredoxin, which has been associated with cancer and tumor growth. DB05448 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, DB05448 is indicated as a potential cancer treatment in combination with chemotherapy for patients with advanced metastatic cancer. Initial trials correlated doses of DB05448 with increased patient survival.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2010624 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23327656 |
2.11 µM [IC50] | ||
Target ID: Q16881|||Q6VB41|||Q6YNQ1 Gene ID: 7296.0 Gene Symbol: TXNRD1 Target Organism: Homo sapiens (Human) |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Normal-phase and stability-indicating reversed-phase high-performance liquid chromatographic methods for the determination of the novel antitumor agent: 1-methylpropyl-2-imidazolyldisulfide. | 2002 Mar 5 |
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The redox protein thioredoxin-1 regulates the constitutive and inducible expression of the estrogen metabolizing cytochromes P450 1B1 and 1A1 in MCF-7 human breast cancer cells. | 2002 Oct |
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Gateways to clinical trials. | 2004 Apr |
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The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging. | 2005 Jan 15 |
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Drug evaluation: the thioredoxin inhibitor PX-12 in the treatment of cancer. | 2006 Dec |
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The antitumor thioredoxin-1 inhibitor PX-12 (1-methylpropyl 2-imidazolyl disulfide) decreases thioredoxin-1 and VEGF levels in cancer patient plasma. | 2006 Feb |
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A Phase I pharmacokinetic and pharmacodynamic study of PX-12, a novel inhibitor of thioredoxin-1, in patients with advanced solid tumors. | 2007 Apr 1 |
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A chemostat study of Streptomyces peucetius var. caesius N47. | 2007 Jan |
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Gateways to clinical trials. | 2007 Jun |
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2-[(1-methylpropyl)dithio]-1H-imidazole inhibits tubulin polymerization through cysteine oxidation. | 2008 Jan |
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Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner. | 2008 May 21 |
Patents
Sample Use Guides
3 hour intravenous infusion as a dose of either 54 mg/m2 or 128 mg/m2 daily for 5 days every three weeks.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23327656
Human lung cancer Calu-6 cells were used for activity evaluation. 1×10^4 cells per well were seeded in 96-well microtiter plates (Nunc). After incubation with the 1, 2, 3, 4 and 5 mkM of PX-12 (DB05448) for the 72 h, MTT solution [20 μl; 2 mg/ml in phosphate-buffered saline (PBS)] was added to each well of the 96-well plates. The plates were additionally incubated for 3 h at 37 °C. Medium was removed from the plates by pipetting, and 200 μl DMSO was added to each well to solubilize the formazan crystals. The optical density was measured at 570 nm using a microplate reader (Synergy™ 2, BioTek Instruments Inc., Winooski, VT, USA).
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C74082
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219104
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DB05448
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141400-58-0
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8PQ9CZ8BTJ
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ACTIVE MOIETY