| Size | Price | |
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| 1mg | ||
| Other Sizes |
| Targets |
Cleavable Linker
Mal-Val-Ala-PABA-cGAMP targets the stimulator of interferon genes (STING) pathway via the cGAMP payload, which is a natural second messenger that activates STING to induce type I interferon and pro-inflammatory cytokine production. The linker enables tumor-targeted delivery of STING agonists. |
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| ln Vitro |
Not available. cGAMP is a potent STING agonist; upon conjugation, the ADC linker-payload is designed to remain inactive in circulation. Following antibody-mediated internalization into target cells, cathepsin-mediated cleavage of the Val-Ala-PABA linker would release active cGAMP to activate STING signaling and promote anti-tumor immune responses.
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| ln Vivo |
Not available. In vivo activity would be evaluated when incorporated into a complete ADC conjugate targeting tumor-associated antigens. STING agonist ADCs have shown the ability to induce tumor regression and activate immune responses in preclinical cancer models, with efficacy assessed by tumor volume reduction, survival extension, and intratumoral immune cell infiltration.
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| Enzyme Assay |
Not available. Standard cathepsin cleavage assays involve incubating Mal-Val-Ala-PABA-cGAMP (1-50 uM) with recombinant cathepsin B (10-100 nM) in acetate buffer (pH 5.0-5.5) containing 2 mM DTT at 37degC for 2-24 hours, followed by HPLC-MS analysis to quantify cGAMP release. Maleimide conjugation efficiency to thiols is assessed by Ellman's assay.
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| Cell Assay |
Not available. For ADC activity assays, typical protocols involve treating STING-expressing cancer cells or STING reporter cells (e.g., THP1-Dual cells) with Mal-Val-Ala-PABA-cGAMP-conjugated antibodies (0.001-100 nM) for 16-24 hours, followed by measurement of IRF3 activation, IFN-beta production, or ISG (interferon-stimulated gene) expression by qPCR or luciferase reporter assays.
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| Animal Protocol |
Not available. For in vivo studies of STING agonist ADCs, standard protocols involve intravenous administration of the ADC conjugate (1-30 mg/kg, single or multiple doses) in tumor-bearing syngeneic mouse models (e.g., CT26, MC38), monitoring tumor volume and body weight for 2-4 weeks, and assessing immune cell activation in tumor and spleen by flow cytometry.
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| ADME/Pharmacokinetics |
Not available. The Val-Ala-PABA linker is designed for serum stability with cathepsin-mediated release in lysosomes. The maleimide group enables stable thiol conjugation to antibodies. cGAMP has poor pharmacokinetics when administered alone but is protected by antibody conjugation, resulting in prolonged circulation.
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| Toxicity/Toxicokinetics |
Not available. Toxicities associated with STING agonists include systemic cytokine release syndrome if not properly targeted. The ADC design aims to minimize off-target STING activation. Specific toxicological data for Mal-Val-Ala-PABA-cGAMP alone are not available, as it is not intended as a free therapeutic agent.
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| References |
[1]. Peter Armstrong Thompson, et al. Composition of antibody construct-agonist conjugates and methods of use thereof. WO2017100305A2.
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| Additional Infomation |
Mal-Val-Ala-PABA-cGAMP is a research-grade ADC linker-payload conjugate for developing STING-targeted antibody-drug conjugates. It has not entered clinical trials nor received regulatory approval. This product is strictly for laboratory research in immuno-oncology and targeted cancer therapy.
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| Molecular Formula |
C46H56N14O20P2
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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 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.) |
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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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