| Size | Price | Stock | Qty |
|---|---|---|---|
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
P-18 targets the PD-1/PD-L1 protein-protein interaction. Specifically, molecular modeling studies indicate that P-18 binds well to the hydrophobic binding interface of the PD-L1 protein. By occupying this site, it prevents PD-L1 from engaging with the PD-1 receptor on T cells, thereby disrupting the inhibitory signal that tumors use to evade immune detection.
|
||
|---|---|---|---|
| ln Vitro |
|
||
| ln Vivo |
|
||
| Enzyme Assay |
The primary in vitro assay for P-18 is the PD-1/PD-L1 homogeneous time-resolved fluorescence (HTRF) binding assay. This assay uses commercial kits to measure the ability of compounds to inhibit the PD-1/PD-L1 interaction. The assay is performed according to the manufacturer's instructions, and the compound's potency (IC₅0) is determined from the resulting fluorescence signal.
|
||
| Cell Assay |
In vitro cellular activity is assessed using a tumor/T-cell co-culture assay. In this model, Hep3B cells engineered to express human PD-L1 and an anti-CD3 antibody are co-cultured with primary human CD3+ T cells. Test compounds, including P-18, are added to the co-culture for 72 hours. The level of T-cell activation is then quantified by measuring the concentration of interferon-gamma (IFN-gamma) released into the supernatant using an ELISA.
|
||
| Animal Protocol |
|
||
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of P-18 have been evaluated in male Sprague-Dawley rats. After a single intravenous dose (1 mg/kg), the half-life (t1/2) was 18.1 +/- 8.3 hours, with a clearance rate of 1.3 +/- 0.4 L/h/kg. Following oral administration (10 mg/kg), the half-life was 20.9 +/- 9.1 hours, and the oral bioavailability (F) was 12%. P-18 also exhibits significantly improved water solubility (17.61 mg/mL) compared to earlier analogues.
|
||
| Toxicity/Toxicokinetics |
In preclinical models, P-18 has shown no apparent toxicity at therapeutic doses. It did not cause cardiotoxicity or myelosuppression in BALB/c mice, indicating a favorable safety profile. These findings suggest that P-18 has a low risk of common dose-limiting toxicities associated with some anticancer agents.
|
||
| References | |||
| Additional Infomation |
P-18 is a novel, small-molecule PD-1/PD-L1 inhibitor with potent in vitro and in vivo activity. As a small molecule, it offers potential advantages over monoclonal antibody-based immunotherapies, including oral bioavailability and a longer half-life. P-18 is a resorcinol diphenyl ether-based compound that binds to PD-L1. It is currently in the preclinical research phase and is not yet approved for clinical use.
|
| Appearance |
Typically exists as solid at room temperature
|
|---|---|
| Chemical Name |
N-(2-aminoethyl)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1'-biphenyl]-3-yl)methoxy)benzyl)piperidine-2-carboxamide
dihydrochloride
|
| Synonyms |
P18 P 18P-18
|
| 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.) |
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
