| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
Target: FFA2 (free fatty acid receptor 2, also known as GPR43). AZ-1729 binds to an allosteric site on FFA2, acting as a direct allosteric agonist and PAM. It enhances propionate-induced Gi signaling (Gi-mediated inhibition of cAMP) without affecting Gq/G11 pathway activation. This pathway bias allows selective modulation of FFA2 functions, including reduced lipolysis, chemotaxis, and insulin secretion.
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| ln Vitro |
In vitro, AZ-1729 inhibits lipolytic effect of isoproterenol in mouse adipocytes with pEC50 = 5.03, and induces migration of human neutrophils. It inhibits forskolin-induced cAMP increase (pEC50 = 6.9) and stimulates 35S-GTPgammaS binding (pEC50 = 7.23). It increases the activity of endogenous short-chain fatty acid propionate in Gi-mediated pathway without affecting Gq/G11-transduced pathway, demonstrating biased agonism.
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| ln Vivo |
In vivo, as a direct allosteric agonist and PAM of FFA2, AZ-1729 is expected to modulate metabolic and immune functions. Potential in vivo applications include reducing adipose tissue lipolysis, improving insulin sensitivity, reducing inflammation, and modulating gastrointestinal function. The compound has not yet been reported in animal efficacy studies but is a tool compound for FFA2 research.
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| Enzyme Assay |
For cell-free FFA2 binding assays: membranes prepared from CHO or HEK293 cells expressing recombinant human FFA2 are incubated with varying concentrations of AZ-1729 (0-100 uM) and the radioligand 3H-propionate (or a fluorescent tracer). Binding affinity (Ki) is measured by radioligand displacement. Alternatively, 35S-GTPgammaS binding assays are performed: membranes are incubated with AZ-1729 (0-100 uM), 35S-GTPgammaS (50-100 pM), and GDP (10-100 uM), and bound radioactivity is measured by filtration and scintillation counting. pEC50 is calculated from dose-response curves (7.23).
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| Cell Assay |
For cell-based assays: CHO or HEK293 cells stably expressing human FFA2 are seeded in 96-well plates. For Gi pathway assessment, cells are pre-incubated with AZ-1729 (0.01-100 uM) for 10-15 min, then stimulated with forskolin (1-10 uM) to induce cAMP production. Intracellular cAMP levels are measured by HTRF (Cisbio) or AlphaScreen kits. Inhibition of cAMP accumulation (Gi activation) is quantified. For Gq/G11 pathway, IP1 accumulation (inositol monophosphate) is measured by HTRF after AZ-1729 stimulation. For chemotaxis assays, human neutrophils are placed in Transwell chambers and allowed to migrate toward AZ-1729 (0.1-100 uM) for 2 h at 37degC. Migrated cells are counted by flow cytometry.
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| Animal Protocol |
For in vivo animal studies: potential protocol involves C57BL/6J mice fed a normal or high-fat diet. AZ-1729 is administered intraperitoneally or orally (5-30 mg/kg) daily for 2-4 weeks. Glucose tolerance tests (IPGTT) are performed. Adipose tissue is harvested for measurement of lipolysis (glycerol and free fatty acid release). Plasma insulin, triglycerides, and inflammatory cytokines (IL-6, TNF-alpha, MCP-1) are measured by ELISA. For inflammation models, DSS-induced colitis or carrageenan-induced paw edema may be used.
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| ADME/Pharmacokinetics |
PK properties of AZ-1729: For a small molecule FFA2 PAM (MW 369.42, ClogP ∼3.1, solubility in DMSO 100 mg/mL), predicted PK in rodents after oral administration: moderate oral bioavailability (∼30-50%), Tmax 1-2 h, plasma half-life 2-4 h. Volume of distribution is moderate (∼2 L/kg). Plasma protein binding is moderate (∼85-90%). Metabolism is primarily via CYP450-mediated oxidation, particularly CYP3A4. The compound can be formulated in DMSO:PEG300:Saline (10:40:50) for in vivo administration. No formal PK studies have been published.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for AZ-1729. Based on FFA2 biology, the receptor is involved in metabolic and immune regulation, and its activation may have beneficial effects. However, FFA2 activation may also cause neutrophilia, gastrointestinal disturbances, and potential off-target effects at high concentrations. No acute toxicity or LD50 studies have been published. The compound is for research use only and not for human consumption.
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| References | |
| Additional Infomation |
AZ-1729 is a research compound not yet approved for clinical use. It is a valuable chemical tool for studying biased signaling at FFA2 and for validating FFA2 as a therapeutic target. It has potential applications in treating metabolic diseases (type 2 diabetes, obesity, insulin resistance), inflammatory diseases (inflammatory bowel disease, arthritis, asthma), and modulating chemotaxis and immune cell function. The pathway bias of AZ-1729 distinguishes it from pan-agonists, making it a unique tool for dissecting FFA2 signaling.
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| Molecular Formula |
C18H16FN5OS
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|---|---|
| Molecular Weight |
369.415945053101
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| Exact Mass |
369.105
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| CAS # |
2016864-46-1
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| PubChem CID |
146018954
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
522
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(SC(=N1)N=C(N)N)C2=CC(=CC=C2)NC(=O)C3=CC=C(C=C3)F
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| InChi Key |
HULFYSCAJVTAAR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H16FN5OS/c1-10-15(26-18(22-10)24-17(20)21)12-3-2-4-14(9-12)23-16(25)11-5-7-13(19)8-6-11/h2-9H,1H3,(H,23,25)(H4,20,21,22,24)
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| Chemical Name |
N-[3-[2-(diaminomethylideneamino)-4-methyl-1,3-thiazol-5-yl]phenyl]-4-fluorobenzamide
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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 | 2.7069 mL | 13.5347 mL | 27.0695 mL | |
| 5 mM | 0.5414 mL | 2.7069 mL | 5.4139 mL | |
| 10 mM | 0.2707 mL | 1.3535 mL | 2.7069 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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