| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
Purity: ≥98%
| Targets |
PR-104 targets DNA in hypoxic tumor cells. As a hypoxia-activated prodrug, it is selectively activated in the low-oxygen environment of solid tumors to generate active DNA cross-linking species. The active metabolite PR-104A forms DNA cross-links, inhibiting DNA replication and repair and leading to cell death.
|
|---|---|
| ln Vitro |
In anoxic rather than aerobic settings, PR-104 (80 μM; 1 h; SiHa cells) exhibits a higher inhibitory impact on radiation-induced DNA single-strand breaks. Ser139 on histone H2AX (gH2AX) is phosphorylated by PR-104 (100 μM; 1 hour; SiHa cells). Following radiation, PR-104 (0.266 mmol/kg; 18 h; SiHa cells) shown efficacy against hypoxic cells. Different cell lines have different potencies of PR-104; H460 cells have the lowest IC50 (0.51 μmol/L) while PC3 prostate cells have the highest (7.3 μmol/L) [1].
In vitro, PR-104 is a hypoxia-activated DNA cross-linking agent that shows marked activity against human tumor cell lines under hypoxic conditions. The compound is non-toxic under normoxic conditions but becomes cytotoxic in hypoxic environments, providing selective targeting of tumor cells. |
| ln Vivo |
The plasma area under the curve is increased by PR-104 (0.56 mmol/kg; iv or ip; 0~2 hours). PR-104 exhibits antitumor activity (0.23 mmol/kg; intraperitoneal; 100 days) [1].
In vivo, PR-104 has demonstrated marked antitumor activity against human tumor xenografts, both as monotherapy and in combination with radiotherapy and chemotherapy. The compound's hypoxia-activated mechanism provides selective toxicity to hypoxic tumor regions, which are typically resistant to conventional therapies. |
| Enzyme Assay |
For enzyme activation assays, PR-104 is incubated with bioreductive enzymes (e.g., cytochrome P450 reductases or nitroreductases) under hypoxic conditions. The conversion of PR-104 to active metabolites such as PR-104A is monitored by HPLC or mass spectrometry. DNA cross-linking is assessed by agarose gel electrophoresis or comet assays.
|
| Cell Assay |
Cellular assays are performed using human tumor cell lines under normoxic and hypoxic conditions. Cells are treated with PR-104 at various concentrations for 24-72 hours. Cell viability is assessed using MTT or clonogenic assays. The hypoxia selectivity ratio (hypoxic IC50 / normoxic IC50) is calculated to determine the compound's therapeutic index.
|
| Animal Protocol |
Animal/Disease Models: CD-1nu/nu mouse
Doses: 0.56 mmol/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)injection or intraperitoneal (ip) injection Experimental Results: plasma area under the curve. Animal/Disease Models: CD1-Foxn1nu mouse Doses: 0.23 mmol/kg Route of Administration: intraperitoneal (ip) injection Experimental Results:demonstrated anti-tumor activity. In vivo studies are conducted in immunocompromised mice bearing human tumor xenografts. PR-104 is administered intravenously at doses determined by preclinical toxicology studies. Tumor volume is measured periodically, and tumor hypoxia is assessed using pimonidazole staining or other hypoxia markers. Combination studies with radiotherapy or chemotherapy may be performed. |
| ADME/Pharmacokinetics |
PR-104 (molecular weight: C14H20BrN4O12PS) is a small-molecule prodrug with favorable pharmacokinetic properties. Upon intravenous administration, it is converted efficiently to the active metabolite PR-104A. The compound's pharmacokinetics are characterized by rapid conversion and distribution to tumor tissues.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity studies have shown that PR-104 is non-toxic under normoxic conditions, with toxicity limited to hypoxic tumor tissues. This selective toxicity profile provides a favorable therapeutic index. The compound has been evaluated in preclinical models for safety and tolerability.
|
| References | |
| Additional Infomation |
PR-104, a nitrogen mustard prodrug, is a non-toxic, small-molecule, hypoxia-activated 3,5-dinitrobenzamide nitrogen mustard prodrug with potential antitumor activity. After intravenous injection, PR-104 is converted to the alcohol intermediate PR-104A by systemic phosphatase. Under hypoxic conditions, PR-104A is reduced intracellularly to nitrogen mustard hydroxylamine PR-104H, which has DNA cross-linking activity. PR-104H specifically cross-links the DNA of hypoxic tumor cells, thereby inhibiting DNA repair and synthesis, leading to cell cycle arrest and apoptosis in hypoxic-susceptible tumor cell populations, without affecting normally oxygenated tissues.
Drug Indications Studied for the treatment of cancer/tumors (unspecified) and solid tumors. Mechanism of Action PR-104 is a novel hypoxia-activated DNA cross-linker with significant activity in human tumor xenograft models, and can be used as monotherapy or in combination with radiotherapy and chemotherapy. Following intravenous injection, PR-104 is converted into the alcohol intermediate PR-104A by systemic phosphatases. Under hypoxic conditions, PR-104A is reduced intracellularly to form the active DNA cross-linking agent, the hydroxylamine compound PR-104H. PR-104H specifically cross-links the DNA of hypoxic tumor cells, thereby inhibiting DNA repair and synthesis, cell cycle arrest, and apoptosis in susceptible hypoxic tumor cell populations, without affecting normal oxygenated tissues. PR-104 is a hypoxia-activated DNA cross-linking agent belonging to the hypoxia-activated prodrug (HAP) class. Its mechanism involves selective activation in hypoxic tumor cells to generate DNA cross-linking species that inhibit DNA replication and repair. The compound has shown marked antitumor activity in preclinical models, both as monotherapy and in combination with radiotherapy and chemotherapy. |
| Molecular Formula |
C14H20BRN4O12PS
|
|---|---|
| Molecular Weight |
579.270962715149
|
| Exact Mass |
577.972
|
| Elemental Analysis |
C, 29.03; H, 3.48; Br, 13.79; N, 9.67; O, 33.14; P, 5.35; S, 5.54
|
| CAS # |
851627-62-8
|
| Related CAS # |
PR-104 sodium;851627-80-0
|
| PubChem CID |
11455973
|
| Appearance |
White to yellow solid powder
|
| LogP |
3.221
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
33
|
| Complexity |
839
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
BrCCN(CCOS(C)(=O)=O)C1C(=CC(=CC=1C(NCCOP(=O)(O)O)=O)[N+](=O)[O-])[N+](=O)[O-]
|
| InChi Key |
GZSOKPMDWVRVMG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C14H20BrN4O12PS/c1-33(28,29)31-7-5-17(4-2-15)13-11(14(20)16-3-6-30-32(25,26)27)8-10(18(21)22)9-12(13)19(23)24/h8-9H,2-7H2,1H3,(H,16,20)(H2,25,26,27)
|
| Chemical Name |
2-((2-bromoethyl)(2,4-dinitro-6-((2-(phosphonooxy)ethyl)carbamoyl)phenyl)amino)ethyl methanesulfonate
|
| Synonyms |
PR 104; PR-104; V16D2ZT7DT; ((2-BROMOETHYL)-2,4-DINITRO-6-(((2-(PHOSPHONOOXY)ETHYL)AMINO)-CARBONYL)ANILINO)ETHYL METHANESULPHONATE; PR104.
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~172.63 mM)
H2O : ~31.25 mg/mL (~53.95 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (8.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (8.63 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7263 mL | 8.6316 mL | 17.2631 mL | |
| 5 mM | 0.3453 mL | 1.7263 mL | 3.4526 mL | |
| 10 mM | 0.1726 mL | 0.8632 mL | 1.7263 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA