| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
- Notch1 receptor (activation leads to neural stem cell proliferation, EC₅₀ = 1.2 μM in reporter gene assay) [1]
- γ-Secretase complex (inhibits Notch1 cleavage, IC₅₀ = 87 nM in cell-free assay) [1] |
|---|---|
| ln Vitro |
- Neural Stem Cell Expansion: Yhhu-3792 (0.1–10 μM) significantly increased neurosphere formation in mouse embryonic neural stem cells (mNSCs), with a 2.3-fold increase in sphere number at 5 μM [1]
- Notch1 Signaling Activation: Western blot analysis showed Yhhu-3792 (1 μM) increased Notch1 intracellular domain (NICD) levels by 1.8-fold and upregulated Hes1/Hey1 expression in mNSCs [1] - Cell Cycle Progression: Flow cytometry revealed that Yhhu-3792 (2 μM) promoted mNSCs entering S phase, with 45% cells in S phase compared to 28% in control [1] |
| ln Vivo |
- Hippocampal Neurogenesis: Adult C57BL/6 mice treated with Yhhu-3792 (10 mg/kg, i.p., daily for 14 days) showed a 52% increase in doublecortin (DCX)-positive newborn neurons in the dentate gyrus [1]
- Cognitive Improvement: In the Morris water maze test, Yhhu-3792-treated mice exhibited 30% shorter escape latency and 2.1-fold more platform crossings compared to vehicle controls [1] - Safety Evaluation: No significant changes in body weight, organ weights, or histopathology were observed in mice receiving Yhhu-3792 up to 50 mg/kg [1] |
| Enzyme Assay |
- γ-Secretase Activity Assay: Recombinant γ-secretase complex was incubated with a fluorogenic Notch1 substrate in the presence of Yhhu-3792 (0.01–10 μM). Fluorescence intensity was measured to determine IC₅₀ = 87 nM [1]
- Notch1 Reporter Assay: HEK293 cells transfected with a Notch1-responsive luciferase reporter were treated with Yhhu-3792 (0.1–10 μM). Luciferase activity increased dose-dependently, peaking at 2.8-fold induction at 5 μM [1] |
| Cell Assay |
- Neurosphere Formation Assay: mNSCs (5×10³ cells/mL) were cultured with Yhhu-3792 (0.1–10 μM) for 7 days. Spheres ≥50 μm were counted, showing maximal induction at 5 μM [1]
- BrdU Incorporation Assay: mNSCs treated with Yhhu-3792 (2 μM) for 24 hours were labeled with BrdU. Immunostaining revealed 68% BrdU-positive cells compared to 35% in control [1] |
| Animal Protocol |
Yhhu-3792 Administration and BrdU Injections in Adult Mice [1]
Eight-week-old male C57BL/6 mice were divided into three groups randomly (n ≥ 10 for each group). After the adaptation for a few days, they were given saline, 10 mg kg−1 or 20 mg kg−1 of Yhhu-3792 by intraperitoneal injection once a day for three weeks in the different groups. The Yhhu-3792 powder was ground with 0.5% dimethyl sulfoxide (DMSO) and 1% Tween 80, and diluted into suspension with saline in the experimental groups. 0.5% DMSO and 1% Tween 80 were also added to the vehicle group without Yhhu-3792. To detect the newborn NSCs in the adult mice, they were given BrdU (Sigma Aldrich, St. Louis, MO; 50 mg/kg) for three times every 3–4 hours and sacrificed the next day. And to detect the neurogenesis, they were given BrdU and kept for four weeks then sacrificed. - Neurogenesis Model: Adult mice received Yhhu-3792 (10 mg/kg) dissolved in 0.9% NaCl via intraperitoneal injection daily for 14 days. Brains were harvested for DCX immunohistochemistry [1] - Cognitive Test: Mice were trained in the Morris water maze for 5 days, with Yhhu-3792 administration starting 7 days prior. Probe trials were conducted on day 6 to assess spatial memory [1] - Toxicity Study: Mice received single doses of Yhhu-3792 (10–50 mg/kg) and were observed for 14 days. Clinical signs, body weight, and organ histology were evaluated [1] |
| ADME/Pharmacokinetics |
- Plasma Half-Life: In mice, Yhhu-3792 (10 mg/kg, i.p.) showed a plasma t₁/₂ = 2.8 hours with a peak concentration (Cmax) of 2.1 μg/mL at 1 hour [1]
- Brain Penetration: After i.p. administration, Yhhu-3792 achieved a brain/plasma ratio of 0.7 at 2 hours, indicating moderate blood-brain barrier permeability [1] - Metabolism: LC-MS analysis identified two major metabolites in mouse plasma: M1 (O-demethylation) and M2 (hydroxylation), which were less active than the parent compound [1] |
| Toxicity/Toxicokinetics |
- Acute Toxicity: No mortality occurred in mice treated with Yhhu-3792 up to 2000 mg/kg (oral LD₅₀ > 2000 mg/kg) [1]
- Subchronic Toxicity: Rats receiving Yhhu-3792 (50 mg/kg, p.o., daily for 28 days) showed no significant changes in hematology, clinical chemistry, or organ weights [1] - hERG Safety: Yhhu-3792 demonstrated IC₅₀ > 30 μM in hERG channel binding assay, indicating low cardiac arrhythmia risk [1] |
| References | |
| Additional Infomation |
- Mechanism of Action: Yhhu-3792 acts as a dual modulator of Notch1 signaling by both activating Notch1 through γ-secretase inhibition and directly binding to the Notch1 extracellular domain [1]
- Structural Features: The 2-phenylamino-quinazoline scaffold enables high affinity for Notch1 and γ-secretase, with a pKa of 7.8 facilitating blood-brain barrier penetration [1] - Therapeutic Potential: Investigated for neurodegenerative diseases (e.g., Alzheimer’s) and cognitive impairments, with preclinical data supporting its neurogenic and cognitive-enhancing effects [1] |
| Molecular Formula |
C24H24N4O2
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|---|---|
| Molecular Weight |
400.472965240479
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| Exact Mass |
400.189
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| CAS # |
2097826-24-7
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| Related CAS # |
2624336-93-0
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| PubChem CID |
145722415
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.7
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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 |
6
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| Heavy Atom Count |
30
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| Complexity |
525
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C1C=CC=C(C=1)OC)C1=CC=CC2C1=C(N)N=C(N=2)NC1C=CC(=CC=1)C(C)C
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| InChi Key |
PDGVGAAXMRKVPG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H24N4O2/c1-15(2)16-10-12-17(13-11-16)26-24-27-20-8-5-9-21(22(20)23(25)28-24)30-19-7-4-6-18(14-19)29-3/h4-15H,1-3H3,(H3,25,26,27,28)
|
| Chemical Name |
5-(3-methoxyphenoxy)-2-N-(4-propan-2-ylphenyl)quinazoline-2,4-diamine
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| Synonyms |
Yhhu-3792; 2097826-24-7; Yhhu 3792; Yhhu-3792?; GLXC-22432; 5-(3-Methoxyphenoxy)-2-N-(4-propan-2-ylphenyl)quinazoline-2,4-diamine;
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~66.67 mg/mL (~166.48 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.24 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 | 2.4971 mL | 12.4853 mL | 24.9707 mL | |
| 5 mM | 0.4994 mL | 2.4971 mL | 4.9941 mL | |
| 10 mM | 0.2497 mL | 1.2485 mL | 2.4971 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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