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| 1mg |
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| Other Sizes |
| Targets |
The conjugate MMC(TMZ)-TOC TFA targets the somatostatin receptor subtype 2 (SSTR2), a G protein-coupled receptor that is overexpressed on the surface of many neuroendocrine tumors (NETs) and other cancers. The "TOC" portion of the molecule is a somatostatin analogue (D-Phe1-Tyr3-octreotide) that has a high binding affinity and selectivity for SSTR2. Upon binding to SSTR2, the conjugate is internalized into the cancer cell. Once inside, the cytotoxic agents MMC and TMZ are released to exert their DNA-damaging effects, leading to cell death.
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| ln Vitro |
In vitro, MMC(TMZ)-TOC TFA is characterized by its high binding affinity and selectivity for SSTR2. The conjugate is designed to target and deliver MMC and TMZ to SSTR2-positive tumor cells. The dual payload approach is intended to create a more potent anti-tumor effect by combining the DNA cross-linking activity of MMC with the DNA alkylating activity of TMZ. Specific IC₅0 values for this conjugate were not provided in the search results.
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| ln Vivo |
No specific in vivo data for MMC(TMZ)-TOC TFA was available in the search results. However, given its high SSTR2 binding affinity, the conjugate is intended for in vivo use to target SSTR2-positive tumors. In a typical preclinical study, the conjugate would be administered intravenously (IV) to mice bearing SSTR2-positive xenografts. The biodistribution would be assessed, and the antitumor efficacy would be measured by tumor growth inhibition. Compared to unconjugated MMC and TMZ, the conjugate is expected to have a higher therapeutic index due to targeted delivery.
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| Enzyme Assay |
The binding affinity of the MMC(TMZ)-TOC TFA conjugate for SSTR2 can be measured using a radioligand binding assay. Membranes from cells overexpressing human SSTR2 are incubated with a radiolabeled somatostatin analogue (e.g., [¹2⁵I]-Tyr3-octreotide) and varying concentrations of the conjugate (0.1-1000 nM). The IC₅0 for competitive displacement of the radioligand is determined. This cell-free assay confirms the high affinity of the TOC moiety for its target. The purity of the conjugate is confirmed by HPLC, and the drug-to-antibody ratio (DAR) is determined by mass spectrometry.
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| Cell Assay |
For cell-based assays, SSTR2-positive cancer cells (e.g., NCI-H69 or NCI-H446 small cell lung cancer cells) are seeded in 96-well plates (5,000-10,000 cells/well). After 24 hours, the cells are treated with varying concentrations of MMC(TMZ)-TOC TFA (0.1-1000 nM). The free drugs MMC and TMZ are used as controls. The cells are incubated for 72-96 hours, and cell viability is measured by MTT or CellTiter-Glo assay. The IC₅0 is calculated and compared to the activity on SSTR2-negative cells to determine the specificity of the conjugate.
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| Animal Protocol |
An in vivo efficacy study would be performed using an SSTR2-positive xenograft model. Female BALB/c nude mice (6-8 weeks old) would be subcutaneously injected with 5×10⁶ SSTR2-positive cells (e.g., NCI-H69 or AR42J cells) in 0.1 mL of PBS/Matrigel (1:1). When tumors reach an average volume of 100-150 mm3, the mice are randomized into groups (n=8-10). MMC(TMZ)-TOC TFA would be formulated in a suitable vehicle (e.g., PBS) and administered intravenously (IV) via the tail vein at doses of 1-10 mg/kg (based on the total drug content) once weekly for 2-4 weeks. Tumor volume would be measured every 2-3 days, and body weight would be monitored.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for MMC(TMZ)-TOC TFA was not available in the search results. As a peptide-drug conjugate (MW 1725.82), it would not be orally bioavailable. It would be administered intravenously. The TFA (trifluoroacetate) counterion is present to improve solubility. The conjugate would be expected to have a short to moderate half-life due to metabolism and clearance. Detailed PK parameters such as t½, Cmax, and AUC were not reported.
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| Toxicity/Toxicokinetics |
No specific toxicological data for MMC(TMZ)-TOC TFA was available in the search results. As a research chemical, standard safety precautions should be followed when handling. This includes wearing appropriate personal protective equipment (PPE) such as gloves, lab coats, and safety goggles. Work should be conducted in a well-ventilated area, such as a chemical fume hood, to avoid inhalation of dust or aerosols. The conjugate contains two potent DNA-alkylating agents and should be handled as a potential carcinogen and genotoxicant.
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| References | |
| Additional Infomation |
MMC(TMZ)-TOC TFA is a research-grade investigational targeted drug conjugate. It is a chemical tool for studying the feasibility of combining SSTR2-mediated targeted drug delivery with multiple DNA-damaging payloads. It is not an FDA-approved drug and is for research use only.
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| Molecular Formula |
C74H99F3N20O21S2
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|---|---|
| Molecular Weight |
1725.82
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| Related CAS # |
MMC(TMZ)-TOC TFA
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| Appearance |
Solid powder
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ≥ 100 mg/mL (~57.94 mM)
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5794 mL | 2.8972 mL | 5.7943 mL | |
| 5 mM | 0.1159 mL | 0.5794 mL | 1.1589 mL | |
| 10 mM | 0.0579 mL | 0.2897 mL | 0.5794 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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