| Size | Price | Stock | Qty |
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| Targets |
Retinoic X receptor (RXR) pan-antagonist. No affinity constants (e.g., IC50, Ki, EC50) are reported in this study. [1]
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| ln Vitro |
In normal human urothelial (NHU) cells, PA452 (0.01, 0.1, and 1 μM) suppresses RXR [2].
In an in vitro system using DKO mouse thymocytes, PA-452 at concentrations up to 1 µM failed to antagonize the effects of 1 nM all-trans-RA on Th1/Th2 development. The presence of PA-452 did not block the RA-induced suppression of IFN-γ production or the enhancement of IL-4 production, as measured by ELISA after re-stimulation with anti-CD3 and anti-CD28 antibodies. [1] In another in vitro system with purified naive CD4+ T cells from DO-11.10 TCR-Tg/RAG-2-deficient mice, PA-452 (1 µM) was added 24 hours after the start of culture along with 10 nM all-trans-RA. PA-452 failed to cancel the effect of all-trans-RA on the induction of IL-4+ and IFN-γ+ cells, as determined by intracellular cytokine staining followed by FACS analysis, whereas the RAR antagonist LE135 was effective. [1] |
| Cell Assay |
For the thymocyte culture experiment, CD4+CD8+ thymocytes from MHC class I and II double-knockout (DKO) mice were stimulated twice with ionomycin and PMA. The cells were then cultured in Step D culture with IL-2, IL-4, and IL-12 (Th1/Th2 condition) in the presence of 1 nM all-trans-RA and graded concentrations of PA-452 (up to 1 µM) for 4 days. To assess functional differentiation, the cells were harvested, washed, and re-stimulated with plate-bound antibodies to CD3 and CD28 for 48 hours. Culture supernatants were collected and the concentrations of IFN-γ and IL-4 were measured by ELISA. [1]
For the naive T cell culture, CD4+CD62Lhigh naive T cells purified from DO-11.10 TCR-Tg/RAG-2-deficient mice were stimulated with plate-bound anti-CD3 and anti-CD28 antibodies in the presence of IL-12 and IL-4 (Th1/Th2 condition). PA-452 (1 µM) and/or all-trans-RA (10 nM) were added 24 hours after the start of culture. After 2 days of stimulation, cells were transferred to new plates and expanded with IL-2 for an additional 4 days. After a total of 6 days of culture, cells were re-stimulated with ionomycin and PMA, and the intracellular expression of IFN-γ and IL-4 was determined by flow cytometry. [1] |
| References |
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| Additional Infomation |
PA-452 is identified as a specific RXR pan-antagonist (reference 31 in the paper). It was used to distinguish the roles of RAR and RXR in the direct regulation of Th1/Th2 development by retinoic acid. The study concluded that since PA-452 could not block the effects of RA, RXR activation is not important for this direct effect, and that RAR (specifically RARα and/or β) is the critical receptor mediating the action of RA on T cell differentiation. This finding contrasts with a previous report by Stephensen et al. (2002) which suggested a role for RXR agonists in enhancing Th2 development; the authors attribute the discrepancy to potential differences in cell purity and indirect effects of other cell types. [1]
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| Molecular Formula |
C26H37N3O3
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|---|---|
| Molecular Weight |
439.590286970139
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| Exact Mass |
439.283
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| CAS # |
457657-34-0
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| PubChem CID |
9803242
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| Appearance |
White to yellow solid powder
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| LogP |
7.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
615
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCCOC1=CC2C(CCC(C)(C)C=2C=C1N(C1=NC=C(C(=O)O)C=N1)C)(C)C
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| InChi Key |
JJUUTJCZMGZJDZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H37N3O3/c1-7-8-9-10-13-32-22-15-20-19(25(2,3)11-12-26(20,4)5)14-21(22)29(6)24-27-16-18(17-28-24)23(30)31/h14-17H,7-13H2,1-6H3,(H,30,31)
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| Chemical Name |
2-((3-(hexyloxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)(methyl)amino)pyrimidine-5-carboxylic acid
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| Synonyms |
PA 452 PA452PA-452
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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 : ~40 mg/mL (~90.99 mM)
Ethanol : ~4.4 mg/mL (~10.01 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.69 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 (5.69 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 | 2.2748 mL | 11.3742 mL | 22.7485 mL | |
| 5 mM | 0.4550 mL | 2.2748 mL | 4.5497 mL | |
| 10 mM | 0.2275 mL | 1.1374 mL | 2.2748 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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