| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
Urokinase-type plasminogen activator receptor (uPAR)[2]
NOTA-AE105 targets the urokinase-type plasminogen activator receptor (uPAR), a glycosylphosphatidylinositol (GPI)-anchored cell surface protein that is overexpressed in various cancers and correlates with poor prognosis. uPAR is involved in extracellular matrix degradation, cell migration, invasion, and metastasis. The AE105 peptide is a high-affinity antagonist of uPAR, binding to a specific site on the receptor and blocking the interaction with its ligand, urokinase plasminogen activator (uPA). When radiolabeled, NOTA-AE105 serves as a PET imaging agent to non-invasively visualize and quantify uPAR expression in tumors, aiding in cancer diagnosis, staging, and therapy monitoring. |
|---|---|
| ln Vitro |
In vitro, NOTA-AE105 (and its radiolabeled versions [⁶⁸Ga]Ga-NOTA-AE105 or [¹⁸F]AlF-NOTA-AE105) shows high binding affinity to uPAR. In competitive binding assays using uPAR-expressing cells (e.g., human prostate cancer cells PC-3, breast cancer MDA-MB-231, or glioblastoma U87MG cells), the radioconjugates exhibit specific binding that can be blocked by excess unlabeled AE105 or uPAR-specific antibodies. The binding affinity (KD) is typically in the low nanomolar range (e.g., 1-10 nM). Cell uptake studies demonstrate that the radiolabeled conjugate is internalized into uPAR-expressing cells in a time-dependent manner, which is important for imaging and potential theranostic applications.
|
| ln Vivo |
In vivo, radiolabeled NOTA-AE105 (e.g., [⁶⁸Ga]Ga-NOTA-AE105 or [¹⁸F]AlF-NOTA-AE105) has been used for PET imaging of uPAR expression in xenograft mouse models of human cancers. In PC-3 prostate cancer xenografts, the radiotracer shows high tumor uptake and good tumor-to-background contrast. uPAR-binding specificity is demonstrated by reduced tumor uptake after co-injection of a blocking dose (excess unlabeled AE105 or uPAR antagonist). The radiotracer clears rapidly from the blood and non-target organs (kidneys are the main route of excretion). Biodistribution studies show accumulation in uPAR-expressing tumors, while non-specific uptake in other organs is low. NOTA-AE105-based PET imaging has successfully been used to monitor the efficacy of anticancer therapies targeting uPAR.
|
| Enzyme Assay |
A typical non-cellular (cell-free) protocol for evaluating the binding affinity of NOTA-AE105 to uPAR involves a radioligand competition binding assay. uPAR protein (e.g., recombinant human uPAR) is immobilized on a 96-well plate (2 microg/well) by overnight incubation at 4degC. The plate is blocked with 3% BSA for 2 hours. Radiolabeled AE105 (e.g., ¹2⁵I-AE105, 0.1 nM) is incubated with the plate in the presence of increasing concentrations of unlabeled NOTA-AE105 (1 pM to 1 microM) for 2 hours at room temperature. After washing, the bound radioactivity is measured in a gamma counter. Non-specific binding is determined in the presence of 1 microM unlabeled AE105. The IC50 and Ki are calculated by fitting the competition curve. Alternatively, surface plasmon resonance (SPR) can be used: uPAR is immobilized on a CM5 chip, and NOTA-AE105 is injected at various concentrations (1-200 nM) to determine the KD.
|
| Cell Assay |
An in vitro cellular protocol for evaluating the uPAR-binding specificity of radiolabeled NOTA-AE105 uses uPAR-expressing human prostate cancer PC-3 cells. Cells are maintained in DMEM with 10% FBS and 1% penicillin/streptomycin at 37degC in 5% CO2. For binding studies, cells are seeded in 12-well plates at 5×10⁵ cells/well and cultured for 48 hours. On the day of the experiment, cells are washed twice with binding buffer (PBS with 0.5% BSA). The radiolabeled tracer ([⁶⁸Ga]Ga-NOTA-AE105 or [¹⁸F]AlF-NOTA-AE105, approximately 1 microCi/well) is added to the cells in 0.5 mL of binding buffer, with or without 100-fold excess of unlabeled AE105 (blocking). After incubation for 30-120 minutes at 4degC (binding) or 37degC (internalization), cells are washed three times with cold PBS. For internalization studies, cells are treated with an acid wash (0.1 M glycine-HCl, pH 2.5) to remove surface-bound tracer, and then lysed with 0.1 M NaOH to measure internalized radioactivity. Radioactivity is measured in a gamma counter. Specific binding is calculated as total minus blocked binding.
|
| Animal Protocol |
An in vivo animal protocol for evaluating [⁶⁸Ga]Ga-NOTA-AE105 as a PET imaging agent uses female NCr nu/nu mice (6-8 weeks old) bearing PC-3 human prostate cancer xenografts. Mice are subcutaneously injected with 5×10⁶ PC-3 cells in 0.1 mL of PBS mixed 1:1 with Matrigel in the right flank. When tumors reach 200-500 mm3 (typically 3-4 weeks), [⁶⁸Ga]Ga-NOTA-AE105 is prepared and purified (specific activity > 10 MBq/nmol, radiochemical purity > 95%). Mice are injected intravenously via the tail vein with 5-10 MBq of the tracer (approximately 0.5-1 microg peptide). For blocking studies, a co-injection group receives a 100-fold excess of unlabeled AE105 (50-100 microg). Dynamic PET scans are acquired for 60-120 minutes post-injection using a small-animal PET scanner. After the scan, mice are euthanized, and organs (tumor, blood, liver, kidney, muscle, bone, etc.) are harvested, weighed, and counted in a gamma counter to calculate the percentage of injected dose per gram (%ID/g). uPAR expression in tumors is confirmed by immunohistochemistry.
|
| ADME/Pharmacokinetics |
Pharmacokinetics for NOTA-AE105 are determined for the radiolabeled version, as the unlabeled peptide is not typically administered. For [⁶⁸Ga]Ga-NOTA-AE105 (MW approximately 1200 Da), the pharmacokinetics are characterized by rapid blood clearance (t½alpha minutes, t½beta ~15-30 minutes). The radiotracer is eliminated primarily through the renal route (kidneys and bladder are the major excretory organs). Uptake in uPAR-positive tumors is rapid, reaching peak levels within 10-30 minutes post-injection, and remains stable for 60-120 minutes. The tumor-to-muscle and tumor-to-blood ratios increase with time due to rapid clearance from non-target tissues. Nonspecific uptake in other organs (liver, lungs) is low due to the hydrophilic nature of the tracer. The favorable pharmacokinetics allow high-contrast PET imaging within 1-2 hours post-injection.
|
| Toxicity/Toxicokinetics |
Toxicity data for NOTA-AE105 are derived from studies using radiolabeled versions for imaging. At the tracer doses used for PET imaging (microgram quantities of peptide, nanogram to microgram amounts of radiometal), no acute toxicity has been observed in animal studies. There are no reports of significant adverse effects on body weight, behavior, or organ function in mice injected with up to 10 microg of NOTA-AE105. The toxicity of the chelator NOTA is low. The AE105 peptide is a uPAR antagonist, but at the low doses used for imaging, it is not expected to have pharmacological effects. Standard radiation safety precautions must be followed when working with radiolabeled versions. The unlabeled NOTA-AE105 is for research use only and should be handled with standard laboratory safety precautions (gloves, lab coat, safety glasses).
|
| References | |
| Additional Infomation |
NOTA-AE105 is a uPAR-targeting peptide conjugate for PET imaging of cancer. AE105 is a small linear peptide antagonist of uPAR with high binding affinity and selectivity (KD in the low nM range). The NOTA chelator allows rapid and stable radiolabeling with ⁶⁸Ga for PET imaging or ¹¹⁷Lu for potential theranostic applications. [⁶⁸Ga]Ga-NOTA-AE105 has been evaluated in preclinical xenograft models of prostate, breast, and colorectal cancers with promising results for non-invasive uPAR imaging. As of 2026, NOTA-AE105-based radiotracers are in preclinical development and have advanced to early clinical studies (e.g., Phase 0 or Phase 1 trials). NOTA-AE105 has not yet received regulatory approval for clinical diagnostic use. It is intended for research use only and may be used as a research tool for uPAR-targeted imaging and therapy.
|
| Exact Mass |
1510.746
|
|---|---|
| CAS # |
1820563-84-5
|
| PubChem CID |
168355625
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
19
|
| Hydrogen Bond Acceptor Count |
24
|
| Rotatable Bond Count |
42
|
| Heavy Atom Count |
108
|
| Complexity |
2990
|
| Defined Atom Stereocenter Count |
9
|
| SMILES |
CC(C)C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)NC(=O)[C@@H](CCCN=C(N)N)NC(=O)[C@@H](CO)NC(=O)[C@H](CC4=CC=CC=C4)NC(=O)[C@H](CC5CCCCC5)NC(=O)[C@H](CC(=O)O)NC(=O)CN6CCN(CCN(CC6)CC(=O)O)CC(=O)O
|
| InChi Key |
QYDKPVWTZOEIPR-WKDKGDAESA-N
|
| InChi Code |
InChI=1S/C72H102N16O20/c1-42(2)30-51(64(100)83-55(68(104)85-58(41-90)71(107)108)34-46-36-76-49-17-10-9-16-48(46)49)79-65(101)54(33-45-19-21-47(91)22-20-45)80-63(99)50(18-11-23-75-72(73)74)78-70(106)57(40-89)84-67(103)53(32-44-14-7-4-8-15-44)81-66(102)52(31-43-12-5-3-6-13-43)82-69(105)56(35-60(93)94)77-59(92)37-86-24-26-87(38-61(95)96)28-29-88(27-25-86)39-62(97)98/h4,7-10,14-17,19-22,36,42-43,50-58,76,89-91H,3,5-6,11-13,18,23-35,37-41H2,1-2H3,(H,77,92)(H,78,106)(H,79,101)(H,80,99)(H,81,102)(H,82,105)(H,83,100)(H,84,103)(H,85,104)(H,93,94)(H,95,96)(H,97,98)(H,107,108)(H4,73,74,75)/t50-,51+,52+,53+,54+,55+,56+,57-,58+/m1/s1
|
| Chemical Name |
(3S)-3-[[2-[4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl]acetyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxy-2-hydroxyethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]amino]-4-oxobutanoic 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO: 83.33 mg/mL (55.12 mM)
|
|---|---|
| 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
