TT-301
TT-301 is a small-molecule immunomodulator capable of penetrating the blood-brain barrier. TT-301 exerts neuroprotective effects by binding to IL-1β, downregulating STAT3 expression, and modulating the JAK-STAT signaling pathway, thereby inhibiting microglial activation and the release of proinflammatory mediators, and alleviating neuroinflammation and brain edema. TT-301 is used in research on traumatic brain injury, intracerebral hemorrhage, subarachnoid hemorrhage, muscle wasting and atrophy, and periodontal disease.
For research use only. We do not sell to patients.
- CAS No.: 886208-76-0
- Formula: C23H21N7
- Molecular Weight:395.46
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
IL-1β |
STAT3 |
In Vitro
TT-301 (1-60 μM; 90 min) hydrochloride inhibits lipopolysaccharide-induced production of pro-inflammatory cytokines and chemokines in BV2 microglia in a dose-dependent manner without reducing cell viability[2].
TT-301 (1-60 μM; 90 min) hydrochloride inhibits lipopolysaccharide-induced production of pro-inflammatory cytokines in EOC20 microglia in a dose-dependent manner without reducing cell viability[2].
TT-301 hydrochloride exhibits effective binding affinity to human IL-1β protein in computer-simulated molecular docking experiments, with a binding energy of -7.8 kcal/mol[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:mouse BV2 microglial cell line
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Concentration:1, 10, 25, 60 μM
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Incubation Time:90 min (pre-incubation); 18 h (with lipopolysaccharide)
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Result:Inhibited lipopolysaccharide-induced production of tumor necrosis factor-α, interleukin-1β, monocyte chemotactic protein-1, and interleukin-6 in a dose-dependent manner.
Did not suppress antiinflammatory cytokine induction in lipopolysaccharide-stimulated cells.
Showed no effect on cell metabolic integrity at tested concentrations.
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Cell Line:mouse EOC20 microglial cell line
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Concentration:1, 10, 25, 60 μM
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Incubation Time:90 min (pre-incubation); 18 h (with lipopolysaccharide)
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Result:Suppressed lipopolysaccharide-induced release of tumor necrosis factor-α, interleukin-1β, monocyte chemotactic protein-1, and interleukin-6 in a dose-dependent manner.
Showed no compromise to cell viability at tested concentrations.
In Vivo
TT-301 (1 mg/kg; i.p.; twice daily; for 5 consecutive days) hydrochloride alleviates cerebral edema and improves vestibular motor function in C57BL/6J mice, without affecting hematoma volume[2].
TT-301 (5 mg/kg; i.p.; once every 12 h; for 7 days after subarachnoid hemorrhage) hydrochloride improves survival rate, ameliorates functional outcomes, and attenuates neuronal injury in female C57BL/6 J mice[5].
TT-301 (5 mg/kg; i.p.; once every 12 h; for 7 days after subarachnoid hemorrhage) hydrochloride induces sustained functional improvement, reduces microgliosis, and modulates cerebral inflammatory cytokine levels in male C57BL/6 J mice[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J mice (closed-skull impact traumatic brain injury model)[2]
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Dosage:1 mg/kg
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Administration:i.p.; twice daily; 5 days; i.p.; twice daily; 28 days; i.v. (first dose at 30 min, 3 h, or 6 h post-injury), then i.p.; twice daily; 5 days
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Result:Reduced F4/80-positive microglial cell counts at 1 and 10 days post-injury.
Reduced Fluoro Jade B-positive degenerating neurons in the hippocampus at 24 h post-injury.
Increased NeuN-positive surviving neurons in the hippocampus to 63025 neurons/mm3 at 28 days post-injury.
Improved Rotorod latency by 52.7% by day 7 post-injury.
Improved Morris water maze latencies by 232.5% at 4 weeks post-injury, and increased time spent in target quadrant to 62.3 seconds during probe testing.
Showed prolonged 28-day treatment did not enhance functional outcomes beyond 5-day treatment.
Retained significant functional benefits with delayed treatment initiation up to 6 h post-injury, with mice spending 56.8 seconds in the target quadrant during probe testing.
Identified 18 genes with ≥ 2-fold differential expression between treated and vehicle groups, with 12 genes directly involved in the Janus kinase-Signal Transducer and Activator of Transcription pathway.
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Animal Model:C57BL/6J mice (collagenase-induced intracerebral hemorrhage model)[2]
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Dosage:1 mg/kg
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Administration:i.p.; twice daily; 5 days
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Result:Did not alter hematoma volume (0.689 mm3 vs. vehicle control).
Reduced cerebral edema to 61.52% brain water vs. vehicle control.
Improved Rotorod performance by 39.6% over the 7-day testing period.
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Animal Model:C57BL/6 J (male, 10-12 weeks old, subarachnoid hemorrhage induced by endovascular filament perforation of the anterior and middle cerebral arteries)[5]
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Dosage:5 mg/kg
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Administration:i.p.; every 12 hours; 7 days (starting 30 minutes post-SAH)
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Result:Improved rotarod latency across the 35-day testing period, with no delayed performance deficit seen on days 6-7.
Improved overall neuroseverity score across the 35-day period.
Increased CatWalk gait speed at days 7 and 35 post-injury, and reduced CatWalk run duration at days 7 and 35.
Reduced number of TMEM119-positive microglia in the caudal cortex at 35 days post-SAH.
Reduced brain levels of proinflammatory KC/GRO/CXCL1 and TARC/CCL1 at 24 hours post-SAH.
Increased brain levels of SDF1/CXCL1 at 24 hours post-SAH.
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Animal Model:C57BL/6 J (female, 10 weeks old, subarachnoid hemorrhage induced by endovascular filament perforation of the anterior and middle cerebral arteries)[5]
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Dosage:5 mg/kg
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Administration:i.p.; every 12 hours; 7 days (starting 30 minutes post-SAH)
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Result:Achieved 73% survival rate over the 35-day period.
Improved rotarod latency throughout the 35-day testing period.
Showed trends toward improvement in neuroseverity score and CatWalk gait speed.
Reduced CatWalk run duration at days 7 and 35.
Reduced number of fluoro-jade C-positive injured hippocampal neurons.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 886208-76-0
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Molecular Weight 395.46
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Formula C23H21N7
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SMILES
C1(N2CCN(C3=NC=CC=N3)CC2)=NN=C(C4=CC=CC=C4)C=C1C5=CC=NC=C5
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Synonyms
MW189; MW01-6-189WH
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TT-301 Related Classifications
HY-111203 Related Classifications
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