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| 50mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Targets |
Fenoldopam hydrochloride targets two distinct molecular entities: the dopamine D1 receptor and lysine-specific demethylase 1 (LSD1). As a D1 receptor partial agonist, Fenoldopam binds to the D1 receptor, which is a G protein-coupled receptor (GPCR) coupled to the Gs protein that activates adenylyl cyclase and increases intracellular cAMP levels. Activation of D1 receptors in vascular smooth muscle cells leads to vasodilation, which reduces peripheral vascular resistance and lowers blood pressure. The compound's selectivity for D1 receptors over D2 receptors contributes to its favorable side effect profile and its ability to improve renal blood flow without causing significant cardiac stimulation. As an LSD1 inhibitor, Fenoldopam binds to the active site of LSD1, a flavin-dependent monoamine oxidase that demethylates histone H3 at lysine 4 (H3K4) and lysine 9 (H3K9), thereby regulating gene expression. LSD1 is overexpressed in various cancers and plays a role in tumor progression, making it an attractive target for anticancer therapy. By inhibiting LSD1, Fenoldopam can alter the epigenetic landscape of cancer cells, leading to re-expression of tumor suppressor genes, induction of differentiation, and inhibition of cell proliferation. The compound's dual mechanism of action makes it a valuable tool for studying both dopaminergic signaling and epigenetic regulation.
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| ln Vitro |
In vitro studies have extensively characterized the biological activities of Fenoldopam hydrochloride in various cell-based systems. As a D1 receptor agonist, Fenoldopam activates D1 receptors in cells expressing the receptor, leading to increased cAMP production and activation of protein kinase A (PKA). In vascular smooth muscle cells, this results in the phosphorylation of myosin light chain kinase and the relaxation of smooth muscle, which is the basis of its vasodilatory effect. In neuronal cells, Fenoldopam modulates dopaminergic signaling and has been used to study the role of D1 receptors in motor control, cognition, and reward. As an LSD1 inhibitor, Fenoldopam has been shown to inhibit LSD1 enzymatic activity with an IC₅₀ of 0.8974 μM in biochemical assays. In cancer cell lines, including breast cancer (MCF-7, MDA-MB-231), lung cancer (A549), and leukemia (HL-60, K562), Fenoldopam treatment at concentrations of 1-10 μM significantly inhibits cell proliferation and induces apoptosis. The compound's anticancer effects are associated with increased H3K4me2 and H3K9me2 levels, re-expression of tumor suppressor genes (e.g., p21, p53), and activation of the mitochondrial apoptotic pathway. Fenoldopam also inhibits cancer cell migration and invasion in transwell assays, suggesting potential anti-metastatic activity. In addition to its effects on cancer cells, Fenoldopam has been shown to modulate immune cell function and reduce the production of pro-inflammatory cytokines in macrophages. The compound's dual activity as a D1 receptor agonist and LSD1 inhibitor makes it a unique pharmacological tool for studying the interplay between dopaminergic signaling and epigenetic regulation in health and disease.
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| ln Vivo |
In vivo studies have demonstrated the therapeutic potential of Fenoldopam hydrochloride in both cardiovascular and oncological applications. As an antihypertensive agent, Fenoldopam is administered intravenously to patients with severe hypertension, including hypertensive emergencies, malignant hypertension, and hypertension with renal impairment. The compound's rapid onset of action (within 5 minutes) and short half-life (approximately 5-10 minutes) allow for precise blood pressure control, and its renal vasodilatory effects increase renal blood flow and improve glomerular filtration rate, making it particularly beneficial for patients with renal dysfunction. In preclinical cancer models, Fenoldopam has been evaluated for its antitumor activity. In mouse xenograft models of breast cancer and leukemia, intraperitoneal administration of Fenoldopam at doses of 5-20 mg/kg significantly inhibited tumor growth and prolonged survival. The antitumor effects were associated with increased H3K4me2 levels, reduced LSD1 activity, and induction of apoptosis in tumor tissues. Fenoldopam has also been shown to enhance the efficacy of other anticancer agents, including chemotherapy and targeted therapy, in combination studies. In models of neurological disorders, Fenoldopam has been used to study the role of D1 receptors in motor function and cognition, with potential applications in Parkinson's disease and schizophrenia. However, the clinical use of Fenoldopam is limited to its approved indication as an antihypertensive agent, and its potential as an anticancer agent remains in the preclinical stage. Further studies are needed to evaluate the efficacy and safety of Fenoldopam in cancer patients and to determine the optimal dosing and combination strategies.
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| Enzyme Assay |
For in vitro receptor binding assays, Fenoldopam hydrochloride is typically evaluated for its affinity to the dopamine D1 receptor using radioligand binding techniques. Membrane preparations from cells expressing the human D1 receptor (e.g., HEK293 or CHO-K1 cells) are incubated with varying concentrations of Fenoldopam (0.01 nM-10 µM) and a fixed concentration of a radiolabeled D1 receptor antagonist, such as ³H-SCH23390 (0.5-2 nM), in binding buffer (50 mM Tris-HCl, pH 7.4, containing 5 mM MgCl₂, 1 mM EDTA, and 0.1% BSA) for 1-2 hours at room temperature. Non-specific binding is determined in the presence of a 100- to 1000-fold excess of unlabeled SCH23390. Bound and free ligand are separated by filtration through glass fiber filters using a cell harvester, and the radioactivity retained on the filters is measured using a liquid scintillation counter. The binding affinity (Ki) is calculated from competition curves using non-linear regression analysis. For functional assays, cells expressing the D1 receptor are loaded with a fluorescent calcium indicator or a cAMP biosensor, and the compound's ability to increase intracellular cAMP or calcium levels is measured. The EC₅₀ for D1 receptor activation is determined from dose-response curves, with dopamine or SKF38393 as positive controls. For LSD1 inhibition assays, recombinant LSD1 enzyme is incubated with varying concentrations of Fenoldopam (0.01-100 µM) and a histone H3 peptide substrate in the presence of the cofactor FAD. The enzymatic activity is measured by monitoring the production of formaldehyde or hydrogen peroxide using a fluorometric or colorimetric assay, and the IC₅₀ is determined from dose-response curves. Selectivity for LSD1 over other histone demethylases is assessed using related enzymes (LSD2, JMJD2, etc.) in similar assays. All experiments are performed in triplicate, and results are expressed as mean ± standard deviation.
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| Cell Assay |
For in vitro cell-based assays, Fenoldopam hydrochloride is evaluated using a panel of cell lines relevant to its pharmacological activities. For D1 receptor signaling studies, cells expressing the D1 receptor (e.g., HEK293-D1R, SH-SY5Y) are treated with Fenoldopam at concentrations of 0.01-10 µM for 5-30 minutes, and cAMP levels are measured using a competitive ELISA or a FRET-based biosensor. For cell proliferation and viability assays, cancer cells (e.g., MCF-7, MDA-MB-231, A549, HL-60) are seeded in 96-well plates at 5 × 10³ cells per well, treated with Fenoldopam (0.1-100 µM) for 24-72 hours, and cell viability is determined using MTT or CellTiter-Glo assays. For apoptosis assays, cells are treated with Fenoldopam for 24-48 hours, and apoptosis is assessed by flow cytometry using Annexin V-FITC/PI staining, caspase-3/7 activity assays, and Western blot analysis of apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3, PARP). For histone methylation studies, cells are treated with Fenoldopam (1-10 µM) for 24-72 hours, and global H3K4me2 and H3K9me2 levels are measured by Western blotting or ELISA. The expression of LSD1 target genes, including p21, p53, and other tumor suppressor genes, is assessed by qPCR. For cell migration and invasion assays, cells are treated with Fenoldopam and tested in transwell or wound-healing assays. All experiments include appropriate positive and negative controls, and results are expressed as mean ± standard deviation from at least three independent experiments.
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| Animal Protocol |
For in vivo animal experiments, Fenoldopam hydrochloride is typically administered intravenously or intraperitoneally to rodents or other animals. For cardiovascular studies, the compound is administered to normotensive or hypertensive rats, and blood pressure and heart rate are monitored using tail-cuff or telemetry methods. For antihypertensive efficacy studies, Fenoldopam is administered as a continuous intravenous infusion or as bolus injections, and the dose-response relationship and duration of action are determined. For renal function studies, the compound's effects on renal blood flow, glomerular filtration rate, and urine output are assessed. For anticancer studies, immunocompromised mice (e.g., BALB/c nude or SCID mice) are subcutaneously inoculated with 1 × 10⁶ to 5 × 10⁶ tumor cells (e.g., MDA-MB-231, A549, HL-60) in the flank. When tumors reach a volume of 50-100 mm³, mice are randomized into treatment groups (n=8-10 per group) and administered Fenoldopam intraperitoneally at doses of 5, 10, or 20 mg/kg/day for 14-21 days. Tumor volume is measured every 2-3 days using a digital caliper, and body weights are recorded daily. At the end of the study, tumors are excised, weighed, and processed for histopathological and immunohistochemical analysis (Ki67, cleaved caspase-3, H3K4me2). For combination studies, Fenoldopam is administered in combination with standard chemotherapeutic agents or targeted therapies. Blood samples are collected for pharmacokinetic analysis and for the measurement of LSD1 activity and histone methylation levels. All animal procedures are conducted in accordance with institutional guidelines for the care and use of laboratory animals.
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| ADME/Pharmacokinetics |
Fenoldopam hydrochloride has well-characterized pharmacokinetic properties due to its clinical use as an antihypertensive agent. The compound has a molecular weight of 342.22 g/mol and a molecular formula of C₁₆H₁₆ClNO₃·HCl. It is administered intravenously, with an onset of action within 5 minutes and a duration of action of approximately 15-30 minutes. The compound has a short elimination half-life of approximately 5-10 minutes, which allows for rapid and precise blood pressure control. Fenoldopam is metabolized in the liver and other tissues via conjugation (glucuronidation and sulfation) and oxidative metabolism, and the metabolites are excreted in urine. The compound does not require dose adjustment in patients with renal impairment, as it improves renal blood flow and does not accumulate in the presence of renal dysfunction. Fenoldopam is approximately 90% bound to plasma proteins, primarily albumin. The compound's pharmacokinetics are linear over the therapeutic dose range, and no significant drug interactions have been reported. For preclinical studies, Fenoldopam can be formulated in saline or other suitable vehicles for intravenous or intraperitoneal administration. The compound is stable when stored as a powder at 4°C or -20°C, protected from light and moisture.
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| Toxicity/Toxicokinetics |
Fenoldopam hydrochloride has a well-established safety profile based on its clinical use as an antihypertensive agent. Common adverse effects associated with Fenoldopam administration include headache, nausea, flushing, and hypotension, which are related to its vasodilatory effects. Serious adverse effects, such as tachycardia, hypotension, and arrhythmias, are rare but may occur at high doses. The compound is contraindicated in patients with known hypersensitivity to Fenoldopam or its components, and in patients with glaucoma, as it may increase intraocular pressure. In preclinical toxicology studies, Fenoldopam has been shown to be well-tolerated at therapeutic doses, with no significant organ toxicity observed in animal studies. However, the compound has not been extensively evaluated for chronic toxicity, genotoxicity, or carcinogenicity, as its clinical use is limited to short-term intravenous administration. As with all research chemicals, appropriate safety precautions should be taken when handling Fenoldopam hydrochloride, including the use of personal protective equipment and working in a well-ventilated fume hood. The compound is for research use only and is not intended for human therapeutic use outside of its approved clinical indication.
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| References | |
| Additional Infomation |
Fenoldopam hydrochloride is an FDA-approved drug for the treatment of severe hypertension in hospitalized patients. It is marketed under various brand names and is available as an intravenous formulation for hospital use. The compound is also known as SKF 82526 and is a synthetic benzazepine analog that acts as a selective D1 receptor partial agonist. Its chemical name is 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol hydrochloride. Fenoldopam has a molecular formula of C₁₆H₁₆ClNO₃·HCl and a molecular weight of 342.22 g/mol. Beyond its antihypertensive effects, Fenoldopam has been identified as a novel LSD1 inhibitor with an IC₅₀ of 0.8974 μM, and it exhibits anti-cancer cell proliferation activity and induces apoptosis in cancer cells. The compound is of significant interest for research in cardiovascular medicine, oncology, and epigenetics, and it continues to be investigated for its potential in cancer therapy and other indications. However, further preclinical and clinical studies are needed to establish its efficacy and safety for these new indications. Fenoldopam hydrochloride is available from various research chemical suppliers for non-clinical studies, with purities typically ≥98% (HPLC). Storage recommendations include keeping the compound in a tightly sealed container, protected from light and moisture, at 4°C or -20°C.
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| Molecular Formula |
C16H17CL2NO3
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| Molecular Weight |
342.21708
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| Exact Mass |
341.059
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| CAS # |
181217-39-0
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| Related CAS # |
Fenoldopam mesylate;67227-57-0;Fenoldopam;67227-56-9
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| PubChem CID |
21642479
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.865
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
22
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| Complexity |
348
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CNCC(C2=CC(=C(C(=C21)Cl)O)O)C3=CC=C(C=C3)O.Cl
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| InChi Key |
NLMPGIXLXSPNFS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H16ClNO3.ClH/c17-15-11-5-6-18-8-13(9-1-3-10(19)4-2-9)12(11)7-14(20)16(15)21/h1-4,7,13,18-21H,5-6,8H21H
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| Chemical Name |
6-Chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol hydrochloride
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| Synonyms |
Fenoldopam HCl, SKF 82526
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9221 mL | 14.6105 mL | 29.2210 mL | |
| 5 mM | 0.5844 mL | 2.9221 mL | 5.8442 mL | |
| 10 mM | 0.2922 mL | 1.4610 mL | 2.9221 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.
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