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| Targets |
The primary target of AAT-008 is the prostaglandin E2 (PGE2) receptor subtype 4 (EP4). EP4 is a G protein-coupled receptor that mediates the effects of PGE2, a key lipid mediator in inflammation and immune regulation. By acting as a potent and selective antagonist, AAT-008 blocks the binding of PGE2 to EP4, thereby inhibiting downstream signaling pathways that promote tumor immune evasion.
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| ln Vitro |
In vitro, AAT-008 demonstrates potent and selective antagonism of the EP4 receptor. It has a Ki of 0.97 nM for recombinant human EP4 and an EC₅₀ of 6.1 nM for recombinant rat EP4. The compound's activity is characterized in radioligand binding and functional assays, confirming its high affinity and selectivity for EP4 over other prostaglandin receptors.
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| ln Vivo |
In vivo, AAT-008 has shown promise in preclinical models by promoting cytotoxic T-cell activity and reducing tumor growth. As an orally active compound, it is being investigated for use in cancer immunotherapy, particularly in combination with immune checkpoint inhibitors like anti-PD-1 antibodies. Its ability to block EP4-mediated immunosuppression makes it a potential candidate for novel cancer treatment strategies.
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| Enzyme Assay |
In vitro receptor binding studies for AAT-008 measure its affinity for the EP4 receptor. Radioligand competition assays are performed using membrane preparations from cells expressing human or rat EP4. The compound competes with a labeled PGE2 ligand for binding, and the Ki values are determined from the competition curves. Selectivity over other prostaglandin receptors is assessed by testing against EP1, EP2, and EP3.
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| Cell Assay |
In vitro cell-based assays for AAT-008 evaluate its functional antagonism at the EP4 receptor. Cells expressing EP4 are treated with a PGE2 agonist in the presence or absence of AAT-008. Receptor activation is measured by downstream signaling, such as cAMP accumulation. The compound's ability to block the agonist-induced response is measured, and IC₅₀ or EC₅₀ values are determined.
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| Animal Protocol |
In vivo animal studies for AAT-008 are conducted in models of cancer immunotherapy. The compound is administered orally, and its effects on tumor growth and immune cell activity are assessed. Combination studies with anti-PD-1 antibodies are performed to evaluate synergistic effects. Pharmacodynamic studies measure EP4 target engagement and downstream signaling in tumor tissues. Pharmacokinetic studies determine the compound's half-life and bioavailability.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of AAT-008 are consistent with an orally active compound. Its molecular weight is 414.81 g/mol. For research use, it is stored as a powder at -20°C for up to 3 years or in solvent at -80°C for up to 1 year. The compound is soluble in DMSO. Further details on its half-life, Cmax, and bioavailability are available from the primary research literature.
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| Toxicity/Toxicokinetics |
The toxicity profile of AAT-008 has not been extensively detailed in the available literature. It is classified for research use only and not for human consumption. As an EP4 antagonist, its potential side effects may include gastrointestinal effects and modulation of immune responses. Standard safety precautions for handling bioactive compounds should be followed.
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| References | |
| Additional Infomation |
Additional information: AAT-008 is also known as AAT008. It is a PGE2 receptor EP4 antagonist. The compound is being investigated for cancer immunotherapy, particularly in combination with immune checkpoint inhibitors. It has shown promise in preclinical models by promoting cytotoxic T-cell activity and reducing tumor growth. This product is for research use only and is not approved for clinical or therapeutic applications.
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| Molecular Formula |
C21H16CLFN2O4
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|---|---|
| Molecular Weight |
414.81
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| Exact Mass |
414.078
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| CAS # |
847727-81-5
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| PubChem CID |
11577792
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
583.4±50.0 °C at 760 mmHg
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| Flash Point |
306.6±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.619
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| LogP |
4.87
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
573
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@H](C1=CC=C(C=C1)C(=O)O)NC(=O)C2=C(N=CC(=C2)Cl)OC3=CC(=CC=C3)F
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| InChi Key |
FKXDPPYCCKCVCW-LBPRGKRZSA-N
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| InChi Code |
InChI=1S/C21H16ClFN2O4/c1-12(13-5-7-14(8-6-13)21(27)28)25-19(26)18-9-15(22)11-24-20(18)29-17-4-2-3-16(23)10-17/h2-12H,1H3,(H,25,26)(H,27,28)/t12-/m0/s1
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| Chemical Name |
4-[(1S)-1-[[[5-Chloro-2-(3-fluorophenoxy)-3-pyridinyl]carbonyl]amino]ethyl]-benzoic acid
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| Synonyms |
AAT 008 AAT008 AAT-008
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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) |
DMSO : ~100 mg/mL (~241.07 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 | 2.4107 mL | 12.0537 mL | 24.1074 mL | |
| 5 mM | 0.4821 mL | 2.4107 mL | 4.8215 mL | |
| 10 mM | 0.2411 mL | 1.2054 mL | 2.4107 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01661192 | COMPLETED | Drug: AAT( Alpha 1 Antitrypsin) | Beta Cell Preservation Type 1 Diabetes |
Rabin Medical Center | 2013-01 | Phase 2 |
Products are for research use only; We do not sell to patients
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