| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
Not applicable. MC-GGFG-NH-CH2-O-CH2-(s-cyclopropane)-COOH is an ADC linker (antibody-drug conjugate linker) for bioconjugation, not a drug. It has no biological target. The MC (maleimidocaproyl) group reacts with thiol groups on antibodies. The GGFG tetrapeptide (Gly-Gly-Phe-Gly) is a cathepsin-cleavable peptide sequence used for controlled payload release within lysosomes. The cyclopropane group may impart conformational rigidity and stability to the linker. The COOH (carboxylic acid) group is available for conjugation to the payload (e.g., Camptothecin).
|
|---|---|
| ln Vitro |
As a linker, MC-GGFG-NH-CH2-O-CH2-(s-cyclopropane)-COOH has no direct biological activity. When conjugated to the cytotoxic agent Camptothecin and then to the antibody Trastuzumab, the resulting ADC exhibits potent cytotoxicity against HER2-positive cancer cells. The GGFG peptide is specifically cleaved by cathepsin B in the lysosome, releasing the active Camptothecin payload. In vitro assays demonstrate high potency with IC50 values in the sub-nanomolar range.
|
| ln Vivo |
No specific in vivo data is reported for this linker alone. ADCs synthesized with this linker (e.g., Trastuzumab-MC-GGFG-Camptothecin) have shown efficacy in HER2-positive tumor xenograft models. The GGFG peptide provides excellent serum stability, as it is not cleaved by serum proteases, ensuring low systemic toxicity. The cyclic structure of the linker may enhance stability and reduce aggregation.
|
| Enzyme Assay |
Not applicable. MC-GGFG-NH-CH2-O-CH2-(s-cyclopropane)-COOH is a chemical reagent for ADC synthesis. A typical conjugation protocol involves activating the COOH group using EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) and HOBt (hydroxybenzotriazole) in DMF. The activated linker is then reacted with an amine-containing payload, such as Camptothecin (or its derivative), to form the drug-linker conjugate. The resulting conjugate is purified by HPLC and then conjugated to the antibody Trastuzumab via maleimide-thiol chemistry after reducing the antibody's interchain disulfide bonds with TCEP.
|
| Cell Assay |
Not applicable. The final ADC is used for cell-based assays. HER2-positive cancer cells (e.g., SK-BR-3, BT-474) and HER2-negative control cells (e.g., MDA-MB-468) are seeded in 96-well plates at 5×103 cells/well. The ADC is applied at concentrations ranging from 0.001 pM to 100 nM for 96 hours. Cell viability is measured by CellTiter-Glo. The IC50 is determined, and the selectivity index is calculated. For mechanism studies, cells are treated with the ADC for 24-72 hours, and Camptothecin-induced DNA damage (gammaH2AX) is measured by immunofluorescence.
|
| Animal Protocol |
No specific in vivo animal study protocols are documented. For an ADC synthesized with this linker, a typical protocol involves establishing subcutaneous xenografts of HER2-positive cancer cells in 6-8 week old female NSG mice. When tumors reach 100-150 mm3, Trastuzumab-MC-GGFG-Camptothecin ADC is administered intravenously at doses of 1-10 mg/kg, once weekly for 2-3 weeks. Tumor volume and body weight are measured twice weekly. At study termination, tumors are excised for analysis of payload release (LC-MS) and apoptosis (TUNEL).
|
| ADME/Pharmacokinetics |
Not applicable for the linker. The final ADC exhibits PK properties typical of Trastuzumab (half-life 7-14 days in mice). The MC-GGFG linker is stable in circulation, with less than 10% payload released after 7 days in mouse plasma. The Camptothecin payload is released intracellularly after lysosomal cathepsin B cleavage. The linker's unique design ensures that the payload is released only inside target cancer cells.
|
| Toxicity/Toxicokinetics |
No toxicity data is reported for MC-GGFG-NH-CH2-O-CH2-(s-cyclopropane)-COOH. As a chemical linker, standard laboratory safety precautions apply. The final Camptothecin-containing ADC must be handled as a highly potent cytotoxic compound, with appropriate containment measures. The compound is for research use only.
|
| Additional Infomation |
MC-GGFG-NH-CH2-O-CH2-(s-cyclopropane)-COOH has the molecular formula C31H40N6O10 and a molecular weight of 656.68. The GGFG tetrapeptide is a cathepsin B-cleavable linker commonly used in ADC technology. Camptothecin is a topoisomerase I inhibitor that causes DNA damage and apoptosis. The maleimide (MC) group selectively reacts with cysteine residues on the antibody. This linker is an example of a third-generation ADC linker designed for optimal stability and controlled payload release.
|
| Molecular Formula |
C31H40N6O10
|
|---|---|
| Exact Mass |
656.281
|
| CAS # |
2626930-84-3
|
| Related CAS # |
MC-GGFG-NH-CH2-O-CH2-cyclopropane-COOH;2778374-70-0
|
| PubChem CID |
169450566
|
| Appearance |
White to light yellow solid powder
|
| Hydrogen Bond Donor Count |
6
|
| Rotatable Bond Count |
21
|
| Heavy Atom Count |
47
|
| Complexity |
1180
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1CC1[C@@H](C(=O)O)OCNC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC(=O)CNC(=O)CNC(=O)CCCCCN3C(=O)C=CC3=O
|
| InChi Key |
SHKYFEZQVRQXHQ-ZTOMLWHTSA-N
|
| InChi Code |
InChI=1S/C31H40N6O10/c38-23(9-5-2-6-14-37-27(42)12-13-28(37)43)32-16-24(39)33-18-26(41)36-22(15-20-7-3-1-4-8-20)30(44)34-17-25(40)35-19-47-29(31(45)46)21-10-11-21/h1,3-4,7-8,12-13,21-22,29H,2,5-6,9-11,14-19H2,(H,32,38)(H,33,39)(H,34,44)(H,35,40)(H,36,41)(H,45,46)/t22-,29-/m0/s1
|
| Chemical Name |
(2S)-2-cyclopropyl-2-[[[2-[[(2S)-2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]methoxy]acetic acid
|
| 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 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)
|
| 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
