| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
HX 531 targets the retinoid X receptor (RXR), a nuclear receptor that forms heterodimers with other nuclear receptors including PPARγ, LXR, RAR, and VDR. As a potent RXR antagonist with an IC50 of 18 nM, HX 531 directly antagonizes PPARγ/RXR signaling. It reduces molecules involved in fatty acid influx and fat formation in skeletal muscle while increasing molecules involved in energy expenditure. The compound promotes white and brown pre-adipocyte differentiation into white adipocytes. It also inhibits bexarotene-induced brown adipogenic reprogramming in myoblasts. The compound enhances activation of the p53-p21Cip1 pathway and abrogates the anti-apoptotic effects of t-RA.
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| ln Vitro |
In vitro, HX 531 (2.5 μM; 30 min) attenuates the anti-apoptotic effect of all-trans retinoic acid (t-RA) in protecting mesangial cells from H₂O₂-induced apoptosis via inhibition of the activator protein 1 (AP-1) pathway. The compound (0.1 μM) has been shown to inhibit RXR-mediated transcriptional activity. HX 531 pre-treatment effectively blocks the protective effects of t-RA against oxidative stress-induced apoptosis. The compound's ability to antagonize RXR signaling has been characterized in various cell lines. Studies have examined its effects on cell differentiation, proliferation, and apoptosis in cancer cells, adipocytes, and other cell types.
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| ln Vivo |
In vivo, HX 531 has been extensively studied for its anti-obesity and metabolic effects. Wild-type mice treated with HX 531 (2 weeks; oral administration) were protected from high-fat diet-induced hyperglycemia and insulin resistance. The weight gain of OLETF rats treated with HX 531 (10 mg/kg/day; 22 weeks; oral administration) was significantly suppressed. HX 531 (0.1% and 0.3% food additive, oral, for two weeks) directly antagonizes PPARγ/RXR, reducing molecules involved in fatty acid influx and fat formation in skeletal muscle while increasing molecules involved in energy expenditure. The compound has been shown to reduce triglyceride content in white adipose tissue, skeletal muscle, and the liver of mice on a high-fat diet.
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| Enzyme Assay |
In cell-free biochemical assays, HX 531 is evaluated for its binding affinity to RXR and its ability to inhibit 9-cis retinoic acid-induced transactivation of RXR. The compound's IC50 of 18 nM is determined using radioligand binding displacement assays and reporter gene assays. Its selectivity for RXR versus other nuclear receptors is characterized. The compound's ability to inhibit RXR-PPARγ heterodimer formation and transcriptional activity is assessed. These assays confirm the compound's mechanism as a potent and selective RXR antagonist.
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| Cell Assay |
Cellular assays for HX 531 involve evaluating its antagonist activity at RXR in various cell lines. The compound's ability to inhibit RXR-mediated transcription is assessed using reporter gene assays. Its effects on cell differentiation are evaluated in pre-adipocyte differentiation models, where HX 531 promotes white adipocyte differentiation. The compound's ability to abrogate the anti-apoptotic effects of t-RA is assessed in mesangial cells and other cell types. Studies have examined its effects on AP-1 pathway inhibition and p53-p21Cip1 pathway upregulation.
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| Animal Protocol |
The effect of HX 531 was studied in male Wistar rats with chronic intrathecal (it.) catheters implanted under ketamine/xylazine anaesthesia. HX 531 was dissolved in DMSO and administered it. in a total volume of 7 µl followed by 5 µl saline flush. Doses of 2 ng and 4 ng were given 10 min before the administration of 10 ng ATRA. Control experiments were performed with equivalent volumes of solvent (DMSO) in separate groups. The compound was tested for its ability to antagonize the pronociceptive effect induced by ATRA. The effect was assessed by measuring withdrawal reflexes to low- and high-intensity mechanical stimulation using Von Frey filaments and to noxious thermal stimulation using a plantar test (55°C radiant heat) at various time points (0, 15, 30, 60, 90 min). Responses were converted to percentage of maximum possible effect (%MPE). Data were analyzed using one-way ANOVA with post hoc Dunnett's test. The dose of 2 ng and 4 ng of HX 531 did not modify the ATRA-induced sensitization effect, indicating lack of antagonism at RXR.
Animal models for HX 531 include high-fat diet-induced obesity models in mice, OLETF rats (a model of type 2 diabetes), and other metabolic disease models. The compound is administered orally or as a food additive. Studies have examined its effects on body weight, insulin sensitivity, glucose homeostasis, and tissue triglyceride content. The compound's ability to prevent high-fat diet-induced obesity, insulin resistance, and diabetes has been demonstrated. Pharmacokinetic parameters are derived from plasma concentration-time curves after oral administration. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for HX 531 show that the compound is orally active and bioavailable. The compound has a molecular weight of 483.56 g/mol with a molecular formula of C29H29N3O4. The CAS number is 188844-34-0. The compound is soluble in DMSO and should be stored as a powder at -20°C for up to 3 years. The SMILES code is CC1(C)C2. Standard pharmacokinetic studies in preclinical species have characterized its absorption, distribution, metabolism, and excretion. The compound's oral bioavailability supports its use in chronic dosing studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of HX 531 is typical of RXR antagonists. As a research compound, standard safety precautions for handling laboratory chemicals apply. The compound is for research use only and not for human use. No specific toxicity studies have been reported in the available literature; however, as a potent receptor antagonist, appropriate handling procedures should be followed. The compound's effects on metabolic pathways suggest that it may have effects on lipid metabolism and energy homeostasis, which should be considered in experimental design.
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| References |
[1]. Ebisawa\net al\n(1999) Retinoid X receptor-antagonistic diazepinylbenzoic acids. Chem.Pharm.Bull. 47\n1778 PMID:10748721 [2]. Alique\net al\n(2006) Vitamin A active metabolite, all-trans retinoic acid, induces\nspinal cord sensitization. II. Effects after intrathecal administration. Br.J.Pharmacol. 149\n65 PMID:16847438 [3]. Suzuki\net al\n(2009) Docosahexaenoic acid induces adipose differentiation-related\nprotein through activation of retinoid X receptor in human\nchoriocarcinoma BeWo cells. Biol.Pharm.Bull. 32\n1177 PMID:19571381 [4]. Nie\net al\n(2017) Brown adipogenic reprogramming induced by a small molecule. Cell Rep. 18\n624 PMID:28099842 |
| Additional Infomation |
HX 531 is a retinoid X receptor (RXR) pan-antagonist. In this study, it was used as a pharmacological tool to investigate whether the pronociceptive effects of all-trans retinoic acid (ATRA) are mediated through RXR or RAR. It was administered intrathecally at doses of 2 ng and 4 ng, but it did not block ATRA-induced spinal sensitization, suggesting that ATRA's action is selective for retinoic acid receptors (RAR) rather than RXR. The compound was kindly donated by H. Kagechika (University of Tokyo). No other pharmacological or toxicological data are reported in this paper.
HX 531 is a potent RXR antagonist with an IC50 of 18 nM. It is orally active and has been extensively studied for its anti-obesity, anti-diabetic, and metabolic effects. The compound prevents high-fat diet-induced obesity, insulin resistance, and diabetes by reducing tissue triglyceride content. It upregulates the p53-p21Cip1 pathway and abrogates the anti-apoptotic effects of all-trans retinoic acid. HX 531 has been used in many studies on retinoid and RXR activity in diabetes and obesity. The compound has a molecular weight of 483.56 g/mol and a formula of C29H29N3O4. The CAS number is 188844-34-0. |
| Molecular Formula |
C29H29N3O4
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| Molecular Weight |
483.558267354965
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| Exact Mass |
483.216
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| CAS # |
188844-34-0
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| PubChem CID |
11755040
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| Appearance |
Light yellow to orange solid powder
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| LogP |
6.916
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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 |
2
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| Heavy Atom Count |
36
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| Complexity |
901
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1(CCC(C2=C1C=C3C(=C2)N(C4=C(C=C(C=C4)[N+](=O)[O-])N=C3C5=CC=C(C=C5)C(=O)O)C)(C)C)C
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| InChi Key |
SXKPGYKPQPYJER-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H29N3O4/c1-28(2)12-13-29(3,4)22-16-25-20(15-21(22)28)26(17-6-8-18(9-7-17)27(33)34)30-23-14-19(32(35)36)10-11-24(23)31(25)5/h6-11,14-16H,12-13H2,1-5H3,(H,33,34)
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| Chemical Name |
4-(5,7,7,10,10-pentamethyl-2-nitro-8,9-dihydronaphtho[2,3-b][1,5]benzodiazepin-12-yl)benzoic acid
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| Synonyms |
HX 531 HX-531 HX531.
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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 : ~33.33 mg/mL (~68.93 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.17 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 (5.17 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0680 mL | 10.3400 mL | 20.6800 mL | |
| 5 mM | 0.4136 mL | 2.0680 mL | 4.1360 mL | |
| 10 mM | 0.2068 mL | 1.0340 mL | 2.0680 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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