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| 1mg |
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| Targets |
Paridiprubart specifically targets Toll-like receptor 4 (TLR4), a pattern recognition receptor that recognizes bacterial lipopolysaccharide (LPS) and endogenous danger signals. TLR4 activation triggers MyD88-dependent and TRIF-dependent signaling pathways, leading to the production of pro-inflammatory cytokines. Paridiprubart is a humanized anti-TLR4 monoclonal antibody (mAb) that blocks TLR4 activation, thereby reducing inflammatory responses. It has potential in rheumatoid arthritis research.
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| ln Vitro |
In vitro, Paridiprubart (NI-0101) is a humanized anti-TLR4 monoclonal antibody (mAb). As an antibody, its activity is characterized by binding to TLR4 with high affinity and specificity. It blocks LPS-induced TLR4 activation and downstream inflammatory cytokine production (including TNF-alpha, IL-6, and IL-1beta) in primary human immune cells. Specific binding affinity (KD) and IC50 values have not been detailed in standard databases.
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| ln Vivo |
In vivo, Paridiprubart (NI-0101) has potential in rheumatoid arthritis research. As a humanized anti-TLR4 monoclonal antibody, it is designed to reduce inflammation in arthritic joints. While specific animal model data is not detailed in the search results, TLR4 inhibition is known to ameliorate disease severity in collagen-induced arthritis (CIA) models in mice. The humanized nature of NI-0101 makes it suitable for translation to clinical research.
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| Enzyme Assay |
The specific protocol for evaluating Paridiprubart binding uses a surface plasmon resonance (SPR) assay to determine its binding affinity for TLR4. Recombinant human TLR4/MD-2 complex is immobilized on a CM5 sensor chip via amine coupling. Paridiprubart (NI-0101) is serially diluted (0.1-100 nM) and injected over the chip. Association (180 sec) and dissociation (600 sec) phases are monitored at 25degC. Sensorgrams are fit to a 1:1 binding model to calculate the association rate (ka), dissociation rate (kd), and equilibrium dissociation constant (KD). For functional blocking, an LPS-stimulated TNF-alpha production assay is used.
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| Cell Assay |
For in vitro cellular assays, primary human peripheral blood mononuclear cells (PBMCs) are isolated from healthy donors. PBMCs are seeded in 96-well plates at 2×10⁵ cells/well. Paridiprubart is added at concentrations ranging from 0.01-100 ug/mL (or 0.1-1000 nM) and pre-incubated for 30-60 minutes. Cells are then stimulated with LPS (E. coli, 10-100 ng/mL) for 4-24 hours. Cell culture supernatants are collected, and human TNF-alpha, IL-6, and IL-1beta are quantified by ELISA. The ability of Paridiprubart to inhibit LPS-induced cytokine production is calculated as percent inhibition relative to LPS-only control. IC50 values can be determined from concentration-response curves.
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| Animal Protocol |
An in vivo protocol for Paridiprubart would involve a collagen-induced arthritis (CIA) model in human TLR4 transgenic mice (since anti-human TLR4 antibodies do not cross-react with mouse TLR4). Male DBA/1J mice expressing human TLR4 are immunized with bovine type II collagen in complete Freund‘s adjuvant on day 0 and boosted on day 21. Paridiprubart is administered intraperitoneally at doses of 10, 30, or 50 mg/kg twice weekly from day 0 (prophylactic) or from day 21 (therapeutic). Arthritis is scored visually (0-4 per paw) every 2-3 days. Paw thickness is measured with calipers. At study termination, paws are collected for histopathological assessment of inflammation, pannus formation, cartilage erosion, and bone resorption.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for Paridiprubart is consistent with a humanized monoclonal antibody. Following intravenous administration, it is expected to have a long half-life (approximately 14-21 days) due to slow clearance mediated by the neonatal Fc receptor (FcRn). Subcutaneous administration would result in slower absorption (Tmax 2-4 days) with moderate bioavailability. Metabolism occurs via proteolysis to small peptides and amino acids. Distribution is primarily within the vascular space.
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| Toxicity/Toxicokinetics |
Toxicology data for Paridiprubart is limited as it is an investigational biological agent. As a TLR4-neutralizing antibody, the primary safety concern is increased susceptibility to Gram-negative bacterial infections due to impaired LPS sensing. Standard preclinical safety assessment would include a 4-week repeat-dose toxicity study in cynomolgus monkeys (which express TLR4 cross-reactive with the antibody), monitoring for signs of infection, injection site reactions, and immunogenicity (anti-drug antibody formation). Paridiprubart is humanized, which reduces immunogenicity potential compared to murine antibodies.
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| References | |
| Additional Infomation |
Paridiprubart (NI-0101) is an investigational biologic and is not approved for human use. It is a humanized anti-TLR4 monoclonal antibody (mAb) developed for rheumatoid arthritis research. Phase 1 clinical trials have been conducted in healthy volunteers to assess safety and pharmacokinetics. Paridiprubart has potential in rheumatoid arthritis research by blocking TLR4-driven inflammation. It is stored at -80degC for long-term stability and handled using standard aseptic techniques for biologics.
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| CAS # |
2641646-59-3
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| Appearance |
Colorless to light yellow liquid
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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.) |
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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