| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
SARS-CoV-2 Mpro (main protease), HIV-1 Reverse Transcriptase, and PARP-1 (Poly [ADP-ribose] polymerase 1). Nigranoic acid inhibits HIV-1 reverse transcriptase, thereby blocking viral replication. Additionally, it interacts with the PARP/AIF signaling pathway, where it downregulates the overactivation of PARP-1. This inhibition prevents the nuclear translocation of AIF, a key step in the apoptotic cascade induced by cerebral ischemia-reperfusion injury, highlighting its dual role in antiviral defense and neuroprotection.
|
|---|---|
| ln Vitro |
In vitro, Nigranoic acid demonstrates significant inhibitory activity against HIV-1 reverse transcriptase, a key enzyme in the viral life cycle. It also exhibits notable inhibition of human neutrophil elastase (HNE) with an IC50 of 3.77 microM, and certain esters show IC50 values ranging from 2.61 to 8.95 microM. Furthermore, it promotes nitric oxide (NO) production via Ca2+ influx, stimulating ERK1/2 phosphorylation, which subsequently influences the expression of BDNF and c-fos, suggesting potential benefits for enhancing mental functions.
|
| ln Vivo |
Blackpiperic acid has a substantial protective impact on cerebral ischemia-reperfusion injury in rats, by inhibiting the excessive activation of PARP and AIF nuclear translocation and downregulating nerve cell apoptosis [2]. Acetic acid (1 mg/kg; ir; 6 hours and 2 hours before cerebral ischemia) significantly reduced cell apoptosis and the expression levels of AIF protein, PARP protein and AIF mRNA at different time periods [2].
In vivo, Nigranoic acid has a strong protective effect against cerebral ischemia-reperfusion injury in rats. Administered at 1 mg/kg via intragastric (i.g.) delivery, 6 and 2 hours before induced brain ischemia, it significantly decreases nerve cell apoptosis. This neuroprotection is achieved by preventing the overactivation of PARP and the subsequent nuclear translocation of AIF. This mechanism leads to reduced expression levels of AIF and PARP proteins, along with decreased AIF mRNA, effectively downregulating the apoptotic signaling cascade. |
| Enzyme Assay |
For PARP-1 inhibition studies, a cell-free ELISA-based assay is used. Recombinant human PARP-1 protein is incubated with a histone-coated plate, biotinylated NAD+, and varying concentrations of the test compound. After the polymerization reaction, streptavidin-HRP is added, followed by a chemiluminescent substrate. Luminescence is measured to quantify PARP-1 activity and calculate the compound‘s IC₅0. Alternatively, for elastase inhibition, the enzyme is incubated with a fluorogenic peptide substrate (MeOSuc-AAPV-AMC) and the compound at 37degC. Fluorescence is monitored to determine inhibition rates.
|
| Cell Assay |
To evaluate neuroprotection or antiviral activity, primary rat cortical neurons or HIV-1 infected T-cells are seeded in 96-well plates and treated with various concentrations of Nigranoic acid for 48-72 hours. Cell viability is measured using the MTT or CCK-8 assay to determine cytotoxicity (CC₅0). For antiviral efficacy, HIV-1 p24 antigen levels in the culture supernatant are quantified by ELISA to calculate the median effective concentration (EC₅0). For neuronal cells, apoptosis markers such as caspase-3 activation are detected via fluorometric assays.
|
| Animal Protocol |
Animal/Disease Models: Sprague–Dawley rat (200-300 g), ischemia-reperfusion model [2]
Doses: 1 mg/kg Route of Administration: intragastric; 6 hrs (hrs (hours)) and 2 hrs (hrs (hours)) before cerebral ischemia Experimental Results: different time points Cell apoptosis was diminished, and the expression levels of AIF protein, PARP protein, and AIF mRNA were diminished. A rat model of middle cerebral artery occlusion (MCAO) is used. Adult male SD rats (200-300g) are administered Nigranoic acid (1 mg/kg) intragastrically 6 hours and 2 hours before induced ischemia. Following a 2-hour occlusion and 24-hour reperfusion, neurological scores are assessed, and brain tissues are collected. Infarct volume is measured using TTC staining. Apoptosis is quantified by TUNEL staining, while AIF and PARP protein levels in the penumbra are analyzed by Western blot and AIF mRNA by qRT-PCR. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for Nigranoic acid is limited. However, as a lipophilic triterpenoid (LogP ~8.5), it is expected to have low aqueous solubility but potentially high membrane permeability. Oral absorption is likely moderate due to its high molecular weight (470.68). Studies indicate that systemic exposure is sufficient to achieve neuroprotective effects in rats. Metabolism likely involves phase I oxidation of the isopropenyl group or the tetracyclic core, followed by phase II conjugation. It displays moderate stability and is primarily distributed to lipid-rich tissues such as the brain.
|
| Toxicity/Toxicokinetics |
Acute toxicity data is not well-documented. In animal models of cerebral ischemia, administration of 1 mg/kg (i.g.) did not produce observable adverse effects or mortality during the study period. However, as with natural products containing alpha,beta-unsaturated acid moieties, there is a potential for minor skin or respiratory irritation upon direct exposure. Long-term toxicological studies have not been published. Standard safety precautions, including the use of personal protective equipment (gloves, lab coats), are recommended when handling the compound in laboratory settings.
|
| References |
|
| Additional Infomation |
Nigranoic acid is a tetracyclic triterpenoid compound with the structure 3,4-open-chain ata-4(28),24-(Z)-diene, substituted with carboxyl groups at positions 3 and 26. It has been isolated from Schisandra henryi and Schisandra propinqua, and exhibits cytotoxic and anti-HIV activity. It functions as a metabolite, an antitumor drug, and an HIV-1 reverse transcriptase inhibitor. It is a tetracyclic triterpenoid compound and also a dicarboxylic acid. Nigranoic acid has been reported to exist in Schisandra propinqua, Kadsura heteroclita, and other organisms with relevant data.
As a natural product isolated from Schisandra chinensis, it acts as a lead compound for developing antiviral and anti-ischemic drugs. Its mechanism of action is distinct from traditional nucleoside reverse transcriptase inhibitors (NRTIs), as it is a natural triterpenoid. It is currently in the preclinical research stage and has not yet entered human clinical trials nor received regulatory approval. Its ability to cross the blood-brain barrier makes it a candidate for central nervous system (CNS) indications. The compound demonstrates unique dual functionality against infectious disease and ischemic injury. |
| Molecular Formula |
C30H46O4
|
|---|---|
| Molecular Weight |
470.68384
|
| Exact Mass |
470.34
|
| CAS # |
39111-07-4
|
| PubChem CID |
10814237
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
7.493
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
34
|
| Complexity |
904
|
| Defined Atom Stereocenter Count |
8
|
| SMILES |
C[C@H](CC/C=C(/C)\C(=O)O)[C@H]1CC[C@@]2([C@@]1(CC[C@]34[C@H]2CC[C@H]([C@]3(C4)CCC(=O)O)C(=C)C)C)C
|
| InChi Key |
NJFOSFIPGRXARF-BRTULJEKSA-N
|
| InChi Code |
InChI=1S/C30H46O4/c1-19(2)22-10-11-24-28(6)14-12-23(20(3)8-7-9-21(4)26(33)34)27(28,5)16-17-30(24)18-29(22,30)15-13-25(31)32/h9,20,22-24H,1,7-8,10-18H2,2-6H3,(H,31,32)(H,33,34)/b21-9-/t20-,22+,23-,24+,27-,28+,29-,30+/m1/s1
|
| Chemical Name |
(Z,6R)-6-[(1S,4R,5R,8S,9S,12S,13R)-13-(2-carboxyethyl)-4,8-dimethyl-12-prop-1-en-2-yl-5-tetracyclo[7.5.0.01,13.04,8]tetradecanyl]-2-methylhept-2-enoic acid
|
| 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 |
| 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) |
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
|
|---|---|
| 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 | 2.1246 mL | 10.6229 mL | 21.2459 mL | |
| 5 mM | 0.4249 mL | 2.1246 mL | 4.2492 mL | |
| 10 mM | 0.2125 mL | 1.0623 mL | 2.1246 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
