TT-301 hydrochloride
TT-301 hydrochloride is a small-molecule immunomodulator capable of penetrating the blood-brain barrier. TT-301 hydrochloride 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 hydrochloride 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.: 1346545-21-8
- Formula: C23H22ClN7
- Molecular Weight:431.93
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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
- Protocols
- 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. Further protocols information, click here.
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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.
Chemical Information
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CAS No. 1346545-21-8
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Molecular Weight 431.93
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Formula C23H22ClN7
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SMILES
Cl.N=1C=CC(=CC1)C2=CC(=NN=C2N3CCN(C4=NC=CC=N4)CC3)C=5C=CC=CC5
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Synonyms
MW189 hydrochloride; MW01-6-189WH hydrochloride
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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.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Research Protocol for Neurological Diseases
PINK1/Parkin-mediated mitophagy pathway is a mitochondrial quality-control signaling axis in which mitochondrial depolarization stabilizes PINK1 on damaged mitochondria, activates Parkin recruitment and E3 ubiquitin ligase activity, promotes ubiquitination of outer mitochondrial membrane proteins, recruits selective autophagy adaptors, and drives lysosomal degradation of damaged mitochondria. In neurological disease research, this pathway is experimentally important because neurons, especially dopaminergic neurons, are highly dependent on mitochondrial integrity, and defective mitochondrial turnover can lead to mitochondrial dysfunction, oxidative stress, impaired neuronal survival, α-synuclein accumulation, and neuroinflammatory damage-associated signals. The genetic disease link is strongest in Parkinson’s disease because mutations in PRKN/parkin cause autosomal recessive juvenile parkinsonism, mutations in PINK1 cause hereditary early-onset Parkinson’s disease, and Drosophila studie
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Pyroptosis Solutions
Pyroptosis is a lytic inflammatory cell-death pathway executed by gasdermin pores, most classically through inflammasome-mediated activation of caspase-1, cleavage of gasdermin D, membrane pore formation, LDH release, and secretion of IL-1β and IL-18. The canonical pathway is commonly modeled by priming cells with an inflammatory signal such as LPS to induce pro-IL-1β and inflammasome components, followed by an activation signal such as ATP or nigericin to activate NLRP3, ASC speck formation, caspase-1 cleavage, GSDMD cleavage, cytokine release, and pyroptotic membrane rupture. The non-canonical pathway is triggered when cytosolic LPS activates mouse caspase-11 or human caspase-4/5, leading to GSDMD cleavage and pyroptosis, and this can secondarily activate NLRP3-dependent IL-1β release. Pyroptosis is linked to inflammatory injury, infection, cancer, liver disease, ocular disease, placental inflammation, and other disease phenotypes, but unresolved questions include which gasdermin fam
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TT-301 hydrochloride Related Classifications
HY-111203A Related Classifications
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