| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Ac-Gly-BoroPro targets fibroblast activation protein (FAP), a serine protease that is overexpressed in cancer-associated fibroblasts and in fibrotic tissues. It acts as a selective inhibitor, with a Ki of 23 nM. The compound forms a reversible boronate complex with the active site of FAP. It selectively inhibits FAP relative to other prolyl peptidases: DPP-4 requires higher concentrations and longer time to reach steady-state inhibition (Ki = 377+/-18 nM); other prolyl peptidases (DPP-7, DPP-8, DPP-9, prolyl oligopeptidase, acylpeptide hydrolase) show Ki values 9- to 5400-fold higher than for FAP.
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| ln Vitro |
Although FAP has been linked to cancer, its precise function is still unknown due to the lack of inhibitors that would separate it from other prolyl peptidases, such dipeptidyl peptidase 4 (DPP-4). FAP is specifically inhibited by Ac-Gly-BoroPro in contrast to other prolyl peptidases. Submicromolar concentrations of Ac-Gly-BoroPro react with FAP easily, and the inhibition levels reach steady-state quickly (Ki=23±3 nM). On the other hand, DPP-4 took longer to attain steady-state inhibition levels (Ki=377±18 nM) and required greater doses of Ac-Gly-BoroPro for inhibition. Other prolyl peptidases (DPP-7, DPP-8, DPP-9, prolyl oligopeptidase, and acyl peptide hydrolase) are inhibited by Ac-Gly-BoroPro with Ki values 9–5400 times greater than that of FAP inhibition. Ac-Gly-BoroPro's N-acyl linkage inhibits the inhibitor's N-terminus, reducing its nucleophilicity and decreasing the likelihood that it will cyclize [1].
In vitro studies have characterized Ac-Gly-BoroPro as a selective and potent FAP inhibitor. FAP reacts readily with submicromolar concentrations of Ac-Gly-BoroPro, reaching steady-state inhibition levels rapidly (Ki=23+/-3 nM). In contrast, DPP-4 requires higher Ac-Gly-BoroPro concentrations for inhibition and a longer time to reach steady-state inhibition levels (Ki=377+/-18 nM). The compound inhibits other prolyl peptidases (DPP-7, DPP-8, DPP-9, prolyl oligopeptidase, and acylpeptide hydrolase) with Ki values ranging from 9- to 5400-fold higher than that for FAP inhibition. The N-acyl-linkage in Ac-Gly-BoroPro blocks the N-terminus, making it less nucleophilic and unlikely to cyclize. |
| ln Vivo |
In vivo studies of Ac-Gly-BoroPro are limited, as it is primarily used as a research tool for in vitro studies. As a FAP inhibitor, it could potentially be used to study the role of FAP in tumor progression, fibrosis, and wound healing in animal models. However, specific in vivo efficacy data are not extensively reported in the available literature. The compound's boron-containing structure suggests that it may be susceptible to oxidative degradation in vivo. Its utility as a tool compound for studying FAP biology in vivo remains to be fully explored.
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| Enzyme Assay |
The in vitro enzyme assay for Ac-Gly-BoroPro involves measuring the inhibition of FAP enzymatic activity. Purified FAP enzyme is incubated with a fluorogenic peptide substrate (e.g., Z-Gly-Pro-AMC) and varying concentrations of the compound. The cleavage of the substrate releases a fluorescent product (AMC), which is measured over time. The initial velocity of the reaction is determined at each concentration, and the Ki value is calculated from the dose-response curve using nonlinear regression analysis. The Ki of 23 nM is determined from these assays. Selectivity is confirmed by testing against other prolyl peptidases.
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| Cell Assay |
In vitro cellular assays for Ac-Gly-BoroPro are conducted using cells that express FAP, such as cancer-associated fibroblasts or FAP-transfected cell lines. Cells are treated with varying concentrations of Ac-Gly-BoroPro. FAP activity in cell lysates or on the cell surface is measured using fluorogenic substrates. The compound's ability to inhibit cellular FAP activity is assessed. Cell viability is evaluated using standard assays such as MTT to ensure that inhibition is not due to cytotoxicity. Selectivity is confirmed by testing in cells expressing other prolyl peptidases. All experiments are performed in triplicate with appropriate controls.
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| Animal Protocol |
In vivo animal studies for Ac-Gly-BoroPro are not extensively reported. As a FAP inhibitor, it could be evaluated in mouse models of cancer or fibrosis. Typical study designs would involve administration of the compound via intraperitoneal or oral routes in tumor-bearing or fibrotic mice. Tumor growth or fibrosis progression would be monitored, and tissues would be collected for histopathological analysis and FAP activity measurement. However, specific published in vivo protocols for Ac-Gly-BoroPro are not available in the provided sources. The compound is primarily used as an in vitro research tool.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for Ac-Gly-BoroPro are not extensively reported. The compound has a molecular weight of 214.03 g/mol and a molecular formula of C8H15BN2O4. It is soluble in DMSO at ≥50 mg/mL (233.61 mM). The compound is unstable in solutions, and freshly prepared solutions are recommended. Storage recommendations: powder at -20degC for up to 3 years or 4degC for 2 years; in solvent at -80degC for 6 months or -20degC for 1 month. Specific pharmacokinetic parameters such as half-life and bioavailability are not provided.
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| Toxicity/Toxicokinetics |
Toxicology data for Ac-Gly-BoroPro are not extensively reported. As a boronic acid-based inhibitor, the compound's safety profile would be related to its reactivity with serine proteases and potential off-target effects. Boronic acids can have toxicity related to their interaction with proteasomes and other enzymes. However, Ac-Gly-BoroPro is a selective FAP inhibitor, which may reduce off-target toxicity. No specific toxicity data, including LD50 values or organ toxicity profiles, are available in the public domain. The compound is for research use only.
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| References | |
| Additional Infomation |
Ac-Gly-BoroPro is a selective fibroblast activation protein (FAP) inhibitor with a Ki of 23 nM. It is a synthetic dipeptide boronic acid that forms a reversible boronate complex with the active site of FAP. The compound exhibits high selectivity over other prolyl peptidases, including DPP-4 (Ki = 377+/-18 nM). Ac-Gly-BoroPro is used as a research tool to study the role of FAP in cancer, fibrosis, and other diseases. It is for research use only and is not approved for therapeutic applications.
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| Molecular Formula |
C8H15BN2O4
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|---|---|
| Molecular Weight |
214.026702165604
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| Exact Mass |
214.112
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| CAS # |
886992-99-0
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| PubChem CID |
102176419
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.520
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| LogP |
-1.21
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
15
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| Complexity |
259
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| Defined Atom Stereocenter Count |
1
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| SMILES |
B([C@H]1CCCN1C(=O)CNC(=O)C)(O)O
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| InChi Key |
UUOZISWTWURDGU-SSDOTTSWSA-N
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| InChi Code |
InChI=1S/C8H15BN2O4/c1-6(12)10-5-8(13)11-4-2-3-7(11)9(14)15/h7,14-15H,2-5H2,1H3,(H,10,12)/t7-/m1/s1
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| Chemical Name |
[(2S)-1-(2-acetamidoacetyl)pyrrolidin-2-yl]boronic acid
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. (3). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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) |
DMSO : ≥ 50 mg/mL (~233.61 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (11.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.6722 mL | 23.3612 mL | 46.7224 mL | |
| 5 mM | 0.9344 mL | 4.6722 mL | 9.3445 mL | |
| 10 mM | 0.4672 mL | 2.3361 mL | 4.6722 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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