| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
RXR α 1.9 μM (Ki) RXR β 0.64 μM (Ki) RXR γ 1 μM (Ki)
HX600 targets RXR-Nurr1 heterodimers. While it is a pan-RXR agonist, its unique activity as an allosteric activator of RXR-Nurr1 and NGFI-B/RXR heterodimers provides a cleaner transcriptional signal, inducing primarily a single gene (CPT1A) for fatty acid oxidation and neuroprotection research, avoiding off-target noise. |
|---|---|
| ln Vitro |
There is no direct neuroprotective impact of HX600 (100-1000 μM, 24 h) on glutamate exposure [1]. HX600 (1 μM, 24 h) reduces inflammation-induced neuronal death and the expression of inflammatory mediators in primary microglia [1].
HX600 acts as an RXR agonist to protect cells. In transient transactivation assays, it activates RXR-Nurr1 heterodimers with an EC50 of 1180 nM and an Emax of 25% in a DR-5 reporter assay. It induces the expression of CPT1A, a key gene in fatty acid oxidation, with high specificity compared to broad RXR agonists. |
| ln Vivo |
HX600 (60 mg/kg, taken orally every 24 hours) enhances immune responses to Iba-1, phospho-p38, and TREM-2 in ischemic brains and lessens ischemic damage and motor impairments in permanent ischemia models[1].
In a permanent middle cerebral artery occlusion (pMCAO) mouse model, HX600 provides significant neuroprotection, reducing ischemic lesion volume by 79%. It also alleviates motor deficits and modulates immunoreactivities of iba-1, phospho-p38, and TREM-2 in the ischemic brain. |
| Enzyme Assay |
Cell-free RXR binding assays are performed using a radioligand competition assay. Purified RXR receptor is incubated with a radiolabeled RXR agonist (e.g., 3H-9-cis-retinoic acid) and varying concentrations of HX600. After incubation, the mixture is passed through a filter to separate bound from free ligand, and the Ki is calculated.
|
| Cell Assay |
Apoptosis Analysis[1]
Cell Types: Primary Cortical Neuron Cells Tested Concentrations: 0 μM, 0.1 μM, 0.2 μM, 0.5 μM, 1 μM, 2 μM, 5 μM, 10 μM, 20 μM Incubation Duration: 24 h Experimental Results: Showd HX600 was not able to prevent the glutamate induced neuronal death. Cell-based assays for RXR are performed in transiently transfected mammalian cells. Cells are co-transfected with expression plasmids for the RXR-Nurr1 heterodimer complex and a luciferase reporter gene (DR-5-Luc). Following treatment with HX600 for 24 hours, luciferase activity is measured to determine the half-maximal effective concentration (EC50) for heterodimer activation. |
| Animal Protocol |
Animal/Disease Models: Ischemic Mice[1]
Doses: 60 mg/kg Route of Administration: po (oral gavage) Experimental Results: Revealed that mice treated with HX600 had smaller lesion with the size of 21%, and significant reduction in Iba-1, phospho-p38 and TREM-2 at protein level. The neuroprotective efficacy of HX600 is evaluated in a mouse model of permanent middle cerebral artery occlusion (pMCAO). The compound is administered orally. Neurological deficits (motor function) are scored. After 72 hours, the animals are sacrificed, and the brains are sectioned and stained with TTC (2,3,5-triphenyltetrazolium chloride) to measure the volume of the ischemic lesion. |
| ADME/Pharmacokinetics |
HX600 is orally bioavailable, which is a key property for its development as a potential neuroprotective therapeutic. This allows for convenient oral administration in preclinical animal models, making it a promising lead compound for central nervous system (CNS) disorders.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity data are not publicly available. However, HX600 is generally described as a research chemical with a specificity profile that avoids broad gene activation, suggesting a potentially more favorable safety profile in terms of mechanism-based toxicities associated with non-selective RXR agonists.
|
| References | |
| Additional Infomation |
The structure given in the first document
HX600 is a research tool for studying RXR-Nurr1-mediated gene expression and neuroprotection. It offers an alternative to bexarotene, a pan-RXR agonist with broader transcriptional activation, potentially providing a cleaner mechanism of action. It is a valuable compound for researching neurodegenerative diseases and ischemic injury where RXR-Nurr1 signaling is involved. |
| Molecular Formula |
C29H30N2O2
|
|---|---|
| Molecular Weight |
438.56
|
| Exact Mass |
438.231
|
| CAS # |
172705-89-4
|
| PubChem CID |
128016
|
| Appearance |
Yellow to orange solid powder
|
| Density |
1.176g/cm3
|
| Boiling Point |
589.595°C at 760 mmHg
|
| Flash Point |
310.376°C
|
| LogP |
6.484
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
33
|
| Complexity |
779
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1(CCC(C2=C1C=C3C(=C2)N(C4=CC=CC=C4N=C3C5=CC=C(C=C5)C(=O)O)C)(C)C)C
|
| InChi Key |
DLFBCHSYAZBTSS-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C29H30N2O2/c1-28(2)14-15-29(3,4)22-17-25-20(16-21(22)28)26(18-10-12-19(13-11-18)27(32)33)30-23-8-6-7-9-24(23)31(25)5/h6-13,16-17H,14-15H2,1-5H3,(H,32,33)
|
| Chemical Name |
4-(5,7,7,10,10-pentamethyl-8,9-dihydronaphtho[2,3-b][1,5]benzodiazepin-12-yl)benzoic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 2.2802 mL | 11.4009 mL | 22.8019 mL | |
| 5 mM | 0.4560 mL | 2.2802 mL | 4.5604 mL | |
| 10 mM | 0.2280 mL | 1.1401 mL | 2.2802 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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