KCL-286
Based on 1 Customer Validation
KCL-286 (C286) is an orally active and brain-penetrant retinoic acid receptor (RAR) β2 agonist (EC50 = 1.9 nM). KCL-286 targets RARβ2 with good selectivity over RAR α (EC50 = 26 nM) and RAR γ (EC50 = 11 nM). KCL-286 activates RARβ2 in the injured neurons. KCL-286 induces axonal regeneration of both spinal and sensory nerves through the inhibitory environment of the CNS, modulates neuroinflammation and extracellular matrix molecules. KCL-286 can modulate the expression of CSPGs by neuronal secretion of decorin which promotes myelination and aids axonal growth. KCL-286 can be studied in research for area such as spinal cord injury and traumatic nerve injury.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 98.93%
- No. CAS: 1952276-71-9
- Fòrmula: C19H14N2O4
- Peso molecular:334.33
-
Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Actividad biológica
-
Chemical Information
-
Solvente y solubilidad
- Pureza y Documentación
- Referencias
-
Help & FAQs
-
Differentiation Inducing Compound Library
HY-L038
-
Reprogramming Compound Library
HY-L039
-
Orally Active Compound Library
HY-L061
-
Transcription Factor-Targeted Library
HY-L090
-
Nuclear Receptor Compound Library
HY-L126
-
Metabolic Enzyme Compound Library
HY-L146
-
Bioactive Compound Library Max
HY-L181
-
MCE Bioactive Compound Library
HY-L001V
-
Bioactive Compound Library
HY-L001
-
High-Throughput Bioactive Compound Library
HY-L205
-
Immunology/Inflammation Compound Library
HY-L007
-
Metabolism/Protease Compound Library
HY-L012
-
CNS-Penetrant Compound Library
HY-L028
Actividad biológica
RAR α (EC50 = 26 nM);RAR β (EC50 = 1.9 nM);RAR γ (EC50 = 11 nM)[1]
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| COS-7 | EC50 |
1.9 nM
Compound: 10
|
Transactivation of GAL4-fused mouse RARbeta-LBD expressed in COS-7 cells after 24 hrs by bright-Glo reagent based assay
Transactivation of GAL4-fused mouse RARbeta-LBD expressed in COS-7 cells after 24 hrs by bright-Glo reagent based assay
|
[PMID: 30792038] |
| COS-7 | EC50 |
13 nM
Compound: 10
|
Transactivation of GAL4-fused mouse RARgamma-LBD expressed in COS-7 cells after 24 hrs by bright-Glo reagent based assay
Transactivation of GAL4-fused mouse RARgamma-LBD expressed in COS-7 cells after 24 hrs by bright-Glo reagent based assay
|
[PMID: 30792038] |
| COS-7 | EC50 |
26 nM
Compound: 10
|
Transactivation of GAL4-fused mouse RARalpha-LBD expressed in COS-7 cells after 24 hrs by bright-Glo reagent based assay
Transactivation of GAL4-fused mouse RARalpha-LBD expressed in COS-7 cells after 24 hrs by bright-Glo reagent based assay
|
[PMID: 30792038] |
| HEK293 | EC50 |
2.05 nM
Compound: 10
|
Transactivation of GAL4 DBD-fused human RARbeta-LBD expressed in HEK293 cells by beta-lactamase reporter gene based assay
Transactivation of GAL4 DBD-fused human RARbeta-LBD expressed in HEK293 cells by beta-lactamase reporter gene based assay
|
[PMID: 30792038] |
KCL-286 (0.1 μM, 72 h) increases the neurite density and the number of synapses to a significant extent which activates RARβ2[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
KCL-286 (3 mg/kg, p.o., every other days for 4 weeks) improves the hind limb locomotor function in moderate thoracic SC contusion rat model[2].
KCL-286 (3 mg/kg, p.o., every other days for 4 weeks) achieves full locomotor and sensory recovery after 3 weeks in C5-T1 dorsal root avulsion rat model[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Non-injured or avulsed male Sprague-Dawley rats[2]
-
Dosage:3 mg/kg, every other days for 4 weeks
-
Administration:Oral gavage (p.o.)
-
Result:Resulted in 82 genes presenting a return to their basal level and 99 genes being strongly upregulated in injured model.
Resulted in 58 genes returning to their basal level after being significantly downregulated under injured conditions.
Significantly modified genes associated with ECM, paths within this signaling complex were both upregulated (those pertaining to the modulation of the cholinergic system, ion transport, and ion channels) or downregulated by the drug after injury.
Highly upregulated the ligand-gated ion channel.
Regulated the G-protein coupled receptor signaling cascades and G-protein coupled receptor protein pathways and chemokine signalling.
Upregulated RARβ in the cell bodies and axons of all neuron subtypes.
-
Animal Model:Moderate thoracic SC contusion male Sprague-Dawley rat model[2]
-
Dosage:3 mg/kg, every other days for 4 weeks
-
Administration:Oral gavage (p.o.)
-
Result:Significantly reduced the tissue loss that progressively occurs at sub-acute and chronic stages following the injury.
Significantly reduced gliosis, shown by reduction in OX42 expression and neuronal loss assessed by neuronal nuclear protein (NeuN) levels.
Significantly lowered the expression of reactive astrocytes Glial fibrillary acidic protein and microglia Ionized Calcium Binding Adaptor Molecule 1.
Significantly upregulated decorin expression and lowered CSPGs in contused rats.
Chemical Information
-
No. CAS 1952276-71-9
-
Appearance Solid
-
Peso molecular 334.33
-
Fòrmula C19H14N2O4
-
Color White to off-white
-
SMILES
CC1=CC=C(C)C2=C1OC(C3=NC(C4=CC=C(C(O)=O)C=C4)=NO3)=C2
-
Synonyms
C286
-
Envío
Room temperature in continental US; may vary elsewhere.
-
Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 6.25 mg/mL (18.69 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
-
Ficha de datos (279 KB)
-
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
-
Instrucciones de manejo (2659 KB)
Referencias
[1]. Goncalves MB, et al. Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamic results of KCL-286, a novel retinoic acid receptor-β agonist for treatment of spinal cord injury, in male healthy participants. Br J Clin Pharmacol. 2023 Jul 15.. [Content Brief]
[2]. Goncalves, M. B., (2024). C286, an orally available retinoic acid receptor β agonist drug, regulates multiple pathways to achieve spinal cord injury repair. Frontiers in molecular neuroscience, 17, 1411384. [Content Brief]
[3]. Borthwick, A. D., et al., (2020). Recent advances in the design of RAR α and RAR β agonists as orally bioavailable drugs. A review. Bioorganic & medicinal chemistry, 28(20), 115664. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.9911 mL | 14.9553 mL | 29.9106 mL | 74.7764 mL |
| 5 mM | 0.5982 mL | 2.9911 mL | 5.9821 mL | 14.9553 mL | |
| 10 mM | 0.2991 mL | 1.4955 mL | 2.9911 mL | 7.4776 mL | |
| 15 mM | 0.1994 mL | 0.9970 mL | 1.9940 mL | 4.9851 mL |
KCL-286 Related Classifications
HY-111573 Related Classifications
Powered by Bioz