| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
Retinol-binding protein 4 (RBP4). (Ki = 8.3 nM, as determined by FRET assay; IC50 = 90 nM for human RBP4 and 66 nM for mouse RBP4 in radioligand displacement assays). It is selective against cellular retinol-binding protein 1 (CRBP1, IC50 > 30 µM) and a panel of other G-protein-coupled receptors, kinases, and enzymes.[1]
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| ln Vitro |
For human RBP4, the IC50 of 1120 is 90 nM, while for mouse RBP4, it is 66 nM[1].
A1120 was identified as a high-affinity, non-retinoid ligand for RBP4 through a scintillation proximity assay screen, displacing radiolabeled retinol. In a fluorescence resonance energy transfer (FRET) assay that measures the RBP4-transthyretin (TTR) interaction, A1120 behaved similarly to fenretinide: it lowered the basal FRET signal and right-shifted the retinol dose-response curve, indicating disruption of the RBP4-TTR complex. The Ki for this interaction was determined to be 8.3 nM.[1] Co-crystallization of A1120 with human RBP4 revealed that it binds to the same central cavity as retinol. The binding induces conformational changes in the loop regions (β3-β4 and β5-β6) at the RBP4-TTR interaction interface, which disrupts the complementary surface required for high-affinity TTR binding, providing a structural mechanism for its activity observed in the FRET assay.[1] |
| ln Vivo |
Acute oral administration of A1120 (30 mg/kg) to B6D2F1 mice significantly lowered serum RBP4 and retinol levels in a time-dependent manner, with peak reduction occurring around 12 hours post-dose. The effect was dose-dependent (measured at 4 hours), with 5 mg/kg and 30 mg/kg doses showing significant reductions. The potency and efficacy in lowering RBP4 and retinol were at least comparable to, if not greater than, fenretinide at equivalent doses.[1]
In chronic studies using diet-induced obese (DIO) B6D2F1 mice, oral administration of A1120 (30 mg/kg/day ad libitum as a diet admixture for 4-6 weeks) significantly lowered serum RBP4 and retinol levels. However, unlike the positive control fenretinide or the PPARγ agonist rosiglitazone, A1120 treatment did not improve insulin sensitivity. It did not significantly alter basal glucose levels, glucose excursion during an insulin suppression test, or glucose and insulin levels during an oral glucose tolerance test, despite achieving greater RBP4 lowering than fenretinide.[1] |
| Animal Protocol |
For acute pharmacodynamic studies, A1120 was prepared in a vehicle of 1% Tween 80 and 1% methylcellulose in water. It was administered orally by gavage to non-fasted, chow-fed B6D2F1 mice (8-10 weeks old) at doses ranging from 0.01 to 30 mg/kg in a volume of 10 ml/kg. Blood was collected via tail nick or terminally at indicated time points for serum analysis of RBP4 and retinol.[1]
For chronic anti-diabetic efficacy studies, diet-induced obese B6D2F1 mice (fed a high-fat diet for 6 weeks) were used. A1120 was prepared as a food admixture based on predetermined average daily food intake to deliver a dose of 30 mg/kg/day. Treatment continued for 4-6 weeks. Body weight and food intake were monitored weekly. Metabolic assessments, including insulin suppression tests and oral glucose tolerance tests, were performed after 4 and 6 weeks of treatment, respectively.[1] |
| References |
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| Additional Infomation |
A1120 (chemical name: 2-(4-(2-(trifluoromethyl)phenyl)piperidin-1-carbamoyl)benzoic acid) is a synthetic small molecule non-retinol ligand that can bind to RBP4. Its discovery helps to study the role of RBP4 in insulin resistance. The results showed that although A1120 can effectively reduce serum RBP4 and retinol levels in vivo, this pharmacological effect does not translate into improved insulin sensitivity in obese and diabetic mouse models. This key finding is supported by data from RBP4 knockout mice, challenges the hypothesis that reducing RBP4 levels is a feasible strategy for treating diabetes, and suggests that the insulin-sensitizing effect of the retinol drug fenritinib may be achieved through a mechanism independent of RBP4. [1]
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| Molecular Formula |
C20H19F3N2O3
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|---|---|
| Molecular Weight |
392.371675729752
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| Exact Mass |
392.135
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| CAS # |
1152782-19-8
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| PubChem CID |
25138295
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| Appearance |
White to off-white solid powder
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| LogP |
4.766
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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 |
3
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| Heavy Atom Count |
28
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| Complexity |
561
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MEAQCLPMSVEOQF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19F3N2O3/c21-20(22,23)16-7-3-1-5-14(16)13-9-11-25(12-10-13)19(28)24-17-8-4-2-6-15(17)18(26)27/h1-8,13H,9-12H2,(H,24,28)(H,26,27)
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| Chemical Name |
2-[[4-[2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]amino]benzoic 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 |
| 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 (~254.86 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5486 mL | 12.7431 mL | 25.4861 mL | |
| 5 mM | 0.5097 mL | 2.5486 mL | 5.0972 mL | |
| 10 mM | 0.2549 mL | 1.2743 mL | 2.5486 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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