| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Cleavable Linker
Mc-Gly-Gly-Phe-Gly-PAB-OH targets the enzymatic activity of Cathepsin B. Upon internalization of the ADC into target cells, the linker is specifically cleaved by Cathepsin B in the lysosomes. This triggers a spontaneous self-immolation of the PAB spacer, releasing the cytotoxic payload (drug) specifically within the target cell, thereby minimizing systemic toxicity. |
|---|---|
| ln Vitro |
An ADC cytotoxin is connected to an antibody by use of an ADC linker to form an ADC.
The in vitro activity of Mc-Gly-Gly-Phe-Gly-PAB-OH is evaluated through its ability to be cleaved by Cathepsin B and release the conjugated payload. In ADC development, this linker is conjugated to a cytotoxic drug (e.g., monomethyl auristatin E or a maytansinoid) and an antibody. The resulting ADC is then tested in cell-based assays to confirm target-specific cytotoxicity. The efficiency of the linker is measured by its ability to selectively kill antigen-positive cancer cells while sparing antigen-negative cells. |
| ln Vivo |
The in vivo activity of Mc-Gly-Gly-Phe-Gly-PAB-OH is demonstrated through the efficacy of the ADCs it helps construct. ADCs utilizing this Cathepsin B-cleavable linker have shown potent anti-tumor activity in preclinical xenograft models. The linker ensures that the cytotoxic payload is released preferentially at the tumor site, leading to tumor regression and improved survival in animal models.
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| Enzyme Assay |
The enzymatic cleavage of Mc-Gly-Gly-Phe-Gly-PAB-OH is typically assessed in vitro using purified Cathepsin B enzyme. The linker is incubated with the enzyme, and the cleavage products are analyzed by HPLC or LC-MS to confirm the release of the payload. The kinetics of the cleavage reaction can also be studied to determine the efficiency of the linker.
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| Cell Assay |
Cellular assays for ADC linkers involve testing the complete ADC molecule (antibody + linker + drug) on target cells. Cells are treated with the ADC, and cell viability is measured using MTT or CellTiter-Glo assays. The specificity of the linker is confirmed by demonstrating that the ADC is only active against cells expressing the target antigen, and that its activity can be blocked by competition with the free antibody.
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| Animal Protocol |
In vivo studies for ADC linkers are conducted in mouse xenograft models. Tumor-bearing mice are administered the ADC via intravenous injection. Tumor volumes are measured at regular intervals, and survival is monitored. The efficacy of the ADC is compared to controls, and the tolerability is assessed by monitoring body weight and clinical signs.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Mc-Gly-Gly-Phe-Gly-PAB-OH are characterized as part of the ADC. The ADC typically has a long half-life in circulation due to the antibody component. The linker is designed to be stable in plasma to prevent premature release of the payload, but readily cleaved in the acidic and protease-rich environment of the lysosome. The stability of the linker in plasma is assessed using LC-MS/MS to measure the release of the payload over time.
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| Toxicity/Toxicokinetics |
Toxicology studies are performed on the final ADC construct. The linker itself is generally considered non-toxic; however, the toxicity of the ADC is dependent on the payload and the target antigen. Standard toxicology assessments include evaluating effects on body weight, clinical chemistry, and histopathology of major organs, particularly the liver and bone marrow, which are common sites of off-target toxicity.
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| Additional Infomation |
Mc-Gly-Gly-Phe-Gly-PAB-OH is a cleavable ADC linker that may be utilized to prepare active antibody conjugated molecules (ADCs). The GGFG sequence is a well-characterized substrate for Cathepsin B, making this linker a valuable tool for the development of targeted cancer therapeutics. It is available with high purity (typically ≥98%) for research and development purposes.
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| Molecular Formula |
C32H38N6O8
|
|---|---|
| Molecular Weight |
634.679527759552
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| Exact Mass |
634.275
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| CAS # |
2632342-05-1
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| Related CAS # |
Mc-Gly-Gly-Phe-Gly-PAB-OH TFA
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| PubChem CID |
146673133
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| Appearance |
White to off-white solid powder
|
| LogP |
-0.2
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
18
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| Heavy Atom Count |
46
|
| Complexity |
1100
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C(CCCCCN1C(C=CC1=O)=O)NCC(NCC(N[C@H](C(NCC(NC1C=CC(CO)=CC=1)=O)=O)CC1C=CC=CC=1)=O)=O
|
| InChi Key |
CTYXSHFYZMWMPD-VWLOTQADSA-N
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| InChi Code |
InChI=1S/C32H38N6O8/c39-21-23-10-12-24(13-11-23)36-28(42)20-35-32(46)25(17-22-7-3-1-4-8-22)37-29(43)19-34-27(41)18-33-26(40)9-5-2-6-16-38-30(44)14-15-31(38)45/h1,3-4,7-8,10-15,25,39H,2,5-6,9,16-21H2,(H,33,40)(H,34,41)(H,35,46)(H,36,42)(H,37,43)/t25-/m0/s1
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| Chemical Name |
6-(2,5-dioxopyrrol-1-yl)-N-[2-[[2-[[(2S)-1-[[2-[4-(hydroxymethyl)anilino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]hexanamide
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5756 mL | 7.8780 mL | 15.7560 mL | |
| 5 mM | 0.3151 mL | 1.5756 mL | 3.1512 mL | |
| 10 mM | 0.1576 mL | 0.7878 mL | 1.5756 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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