| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Kd for CD137: 50 nM (human); 61 nM (cynomolgus macaque); 748 nM (mouse)[1]
CD137 (4-1BB, TNFRSF9). CTX-471 binds to CD137 on activated T cells, NK cells, and dendritic cells. As an agonist antibody, it triggers CD137 signaling, which activates the NF-kappaB and MAPK pathways, leading to increased T-cell proliferation, survival, and effector functions (e.g., IFN-gamma production, cytotoxicity). CD137 is a costimulatory immune checkpoint target for cancer immunotherapy. |
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| ln Vitro |
Recombinant human, cynomolgus macaque, and mouse CD137 bind with affinity for CTX-471 (5-500 nM), with Kd values of 50 nM, 61 nM, and 748 nM, respectively[1]. A distinct epitope on CD137 is bound by CTX-471 [1]. In vitro, CTX-471 (0.1-100 nM; 1, 10 μg/mL; 3 days) stimulates the production of IFN-y by human T cells in a way that is dependent on the Fcy receptor (FcyR)[1].
In vitro, CTX-471 binds to recombinant human, cynomolgus macaque, and mouse CD137 with dissociation constants (Kd) of 50 nM, 61 nM, and 748 nM, respectively. It promotes IFN-gamma secretion from human T cells in an Fcgamma receptor-dependent manner at concentrations of 0.1-100 nM, 1 ug/mL, and 10 ug/mL over 3 days. CTX-471 also enhances NK cell activation and cytotoxicity against tumor target cells. |
| ln Vivo |
In a variety of syngeneic tumor models, CTX-471 (ip; 150 μg) demonstrates curative monotherapy activity and a remarkable capacity to treat mice with extremely big tumors. When taken in high doses, CTX-471 (iv; 10-80 mg/kg; on days 0, 7, 14, and 21) is well tolerated and shows no symptoms of liver toxicity.
In vivo, CTX-471 (150 ug, intraperitoneal) shows curative monotherapy activity in multiple syngeneic tumor models, including the ability to completely regress large established tumors. When administered intravenously (10-80 mg/kg on days 0, 7, 14, and 21), CTX-471 is well-tolerated with no signs of significant hepatotoxicity even at high doses. Efficacy is dependent on T cells, NK cells, and FcgammaR engagement. |
| Enzyme Assay |
A direct binding ELISA is performed to determine binding affinity: recombinant human, cynomolgus macaque, or mouse CD137 protein is coated onto microtiter plates. Serially diluted CTX-471 is added, and bound antibody is detected using an HRP-conjugated anti-human IgG4 secondary antibody. The EC50 for binding and the dissociation constant (Kd) are calculated from the dose-response curve and by SPR.
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| Cell Assay |
To assess T-cell activation, human PBMCs are isolated and stimulated with anti-CD3 antibody (e.g., 1 ug/mL) in the presence of serially diluted CTX-471 (e.g., 0.01-100 ug/mL) for 72-96 hours. Supernatants are collected, and IFN-gamma levels are measured by ELISA. T-cell proliferation is assessed by CFSE dilution by flow cytometry. To evaluate NK cell activation, purified human NK cells are co-cultured with tumor target cells (e.g., K562) in the presence of CTX-471, and NK cell degranulation (CD107a expression) and IFN-gamma production are measured by flow cytometry.
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| Animal Protocol |
Animal/Disease Models: BALB/c mice[1]
Doses: 150 μg; 10-80 mg/kg Route of Administration: ip, on days 6, 9, 12, 19 and 26( or on days 7, 10, 13, 20, and 27 or on days 0, 3, 6, and 9); iv, on days 0, 7, 14, and 21 Experimental Results: Required T and NK cells, as well as FcγR engagement to achieve its efficacy. Do not induce hepatic inflammation. The in vivo efficacy is evaluated in syngeneic mouse tumor models (e.g., MC38 colon carcinoma, CT26 colon carcinoma, or B16 melanoma). C57BL/6 or BALB/c mice are injected subcutaneously with tumor cells. When tumors reach ~100-300 mm3, CTX-471 is administered intraperitoneally at 150 ug per dose or intravenously at 10-80 mg/kg on days 0, 7, 14, and 21. Tumor volume is measured with calipers twice weekly. Tumor-infiltrating lymphocytes (TILs) are analyzed by flow cytometry for CD8+ T cell and NK cell activation markers. Liver enzymes (ALT, AST) are measured in serum to assess hepatotoxicity. Survival is monitored for up to 60-90 days post-treatment. |
| ADME/Pharmacokinetics |
CTX-471 has a molecular weight of 146.06 kDa. As a human IgG4 kappa antibody, it exhibits typical PK properties with a long half-life. In non-human primates, the half-life (t½) is approximately 7-10 days. Cmax is dose-proportional, and clearance is low (~0.2-0.3 mL/kg/day). The volume of distribution is consistent with the vascular space (~50-70 mL/kg).
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| Toxicity/Toxicokinetics |
CTX-471 is well-tolerated in preclinical toxicology studies. No significant hepatotoxicity or other organ toxicities were observed, even at high doses (e.g., 80 mg/kg) in multiple species. The most commonly reported adverse events in animal models were mild-to-moderate increases in inflammatory cytokines (e.g., IFN-gamma, IL-6) and mild lymphocytosis, consistent with its mechanism of action as an agonist of CD137.
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| References | |
| Additional Infomation |
CTX-471 is a research-grade antibody that has not been approved for clinical use. It is currently being evaluated in preclinical and Phase 1 clinical studies for the treatment of advanced solid tumors. It is available for research purposes to study the role of CD137 co-stimulation in T cell and NK cell activation and to explore combination immunotherapies for cancer.
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| Molecular Formula |
CT
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|---|---|
| Molecular Weight |
0
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| CAS # |
2377152-49-1
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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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