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| 2mg |
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CP21 is a bifunctional immunomodulatory small molecule targeting PD-L1 and CXCL12 with high affinities. With an IC50 of 78.6 nM (HTRF assay), CP21 had the strongest anti-PD-L1 effects. hCXCL12 and mCXCL12 both bind CP21 in a dose-dependent manner with a KD of 160 nM and 76.5 nM, respectively. Additionally, by triggering the immune system, it showed strong in vivo antitumor effectiveness. CP21 is a potential dual immunotherapy agent for the treatment of cancer because it is a first-in-class dual PD-L1/CXCL12 inhibitor that merits further research.
| Targets |
CP21 targets two key immunosuppressive biomacromolecules in the tumor microenvironment: programmed death-ligand 1 (PD-L1) and C-X-C motif chemokine ligand 12 (CXCL12). It binds to human PD-L1 with a KD of 66.9 nM and mouse PD-L1 with a KD of 70.1 nM. For CXCL12, it binds to human CXCL12 with a KD of 160 nM and mouse CXCL12 with a KD of 76.5 nM.
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| ln Vitro |
In vitro, CP21 potently inhibits the PD-1/PD-L1 interaction with an IC50 of 78.6 nM in a homogeneous time-resolved fluorescence (HTRF) assay. It dose-dependently inhibits CXCL12-mediated Ca2+ cellular responses and cell migration. Furthermore, CP21 significantly promotes interferon release and enhances the ability of immune cells to kill tumor cells.
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| ln Vivo |
In vivo, CP21 demonstrates strong antitumor efficacy in mouse models. In a B16-F10 melanoma model, oral administration at 125 mg/kg achieved a tumor growth inhibition (TGI) of 58.5%. It also showed efficacy in a CT-26 colon cancer model. Mechanistically, CP21 treatment dose-dependently increases the infiltration of CD3+ and CD3+CD8+ cytotoxic T lymphocytes (CTLs) into tumors, thereby activating the tumor immune microenvironment.
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| Enzyme Assay |
The binding affinity of CP21 to its targets is typically assessed using Surface Plasmon Resonance (SPR) to measure the KD values for PD-L1 and CXCL12. Circular Dichroism (CD) spectroscopy is used to confirm conformational changes in the secondary structures of these target proteins upon compound binding. Isothermal Titration Calorimetry (ITC) further validates the binding and identifies the interactions as primarily hydrophobic.
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| Cell Assay |
Functional cellular assays are used to validate CP21's dual inhibitory activity. The inhibition of CXCL12 is confirmed by measuring the compound's ability to dose-dependently block CXCL12-induced calcium flux in THP-1 cells. The inhibition of the PD-1/PD-L1 axis is validated using co-culture models of cancer cells and immune cells, such as Hep3B & PBMC or Jurkat T & B16-F10, where enhanced immune cell activity is measured.
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| Animal Protocol |
In vivo efficacy studies are performed in syngeneic mouse tumor models, such as B16-F10 melanoma and CT-26 colon carcinoma. CP21 is typically administered via oral gavage. Antitumor activity is evaluated by measuring tumor volume and weight, while immune activation is assessed by analyzing tumor-infiltrating lymphocytes (TILs) using flow cytometry.
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| ADME/Pharmacokinetics |
In male Sprague-Dawley rats, oral administration of CP21 (18 mg/kg) resulted in a plasma exposure (AUC(0-t)) of 127.5 +/- 4.8 ng/mL h. Intravenous administration (1 mg/kg) showed a higher exposure (AUC = 2032.5 +/- 11.44.8 ng/mL h) and a lower clearance rate (0.5 +/- 0.1 L/h/kg). The oral bioavailability is considered low but acceptable.
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| Toxicity/Toxicokinetics |
In preclinical mouse models, CP21 did not induce significant hepatotoxicity or nephrotoxicity based on serum biochemistry. It also did not cause cardiotoxicity as measured by creatine kinase isoenzyme assays. Histological analysis (H&E staining) revealed no apparent morphological aberrations in major organs, and no marked changes in body weight were observed during treatment.
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| References | |
| Additional Infomation |
CP21 is a research-grade compound and is not approved for clinical use. It was discovered by a team at Southern Medical University and reported in a 2023 publication in *Signal Transduction and Targeted Therapy*. As a first-in-class dual PD-L1/CXCL12 inhibitor, CP21 represents a novel strategy for dual immunotherapy. It is available from research chemical suppliers for non-human use.
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| Appearance |
Typically exists as solid at room temperature
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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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