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Purity: ≥98%
TRC051384 is a novel compound which can potently induce HSPA1A/B (heat shock protein) expression and subsequent Hsp70 production via heat shock factor-1 (HSF1) activation. It has the potential to be developed as a novel pharmacological agent for the treatment of ischemic stroke. RC051384 induces heat shock protein 70 (HSP70) and is a potent anti-inflammatory agent. TRC051384, dose dependently induces HSP70B mRNA by several hundred folds in both HeLa and rat primary mixed neurons. Treatment with TRC051384 results in significant dose-dependent increase in HSF1 transcriptional activity and recovery of luciferase activity. TRC051384 results in 60% inhibition at 6.25 μM and 90% inhibition at 12.5 μM of LPS-induced TNF-α expression in differentiated THP-1 cell line.
| Targets |
Induces Heat Shock Protein 70 (HSP70) expression [1]
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| ln Vitro |
TRC051384, in both HeLa and rat primary mixed neurons, dose-dependently increases HSP70B mRNA by several hundred fold. Treatment with TRC051384 causes luciferase activity to recover and HSF1 transcriptional activity to significantly increase in a dose-dependent manner. In differentiated THP-1 cell line, TRC051384 inhibits TNF-α expression induced by LPS by 60% at 6.25 μM and 90% at 12.5 μM[1].
TRC051384 (0.1-10 μM) dose-dependently induced HSP70 protein expression in primary cortical neurons, with a 2.8-fold increase at 10 μM compared to vehicle controls [1] - In an oxygen-glucose deprivation (OGD) model of ischemic injury, TRC051384 (1 μM) improved primary cortical neuron survival rate from 35% to 68% after 24-hour reperfusion; reduced LDH release (a marker of cell damage) by 40% [1] - TRC051384 (10 μM) showed no significant cytotoxicity to normal primary cortical neurons, with cell viability >90% after 48 hours of treatment [1] - Western blot analysis confirmed that TRC051384 -mediated neuroprotection was associated with elevated HSP70 levels, as HSP70 knockdown abolished the protective effect [1] |
| ln Vivo |
Even when given eight hours after the onset of ischemia, treatment with TRC051384 significantly reduces stroke associated neuronal injury and disability in a rat model of transient ischemic stroke (87% reduction in area of penumbra recruited to infarct and 25% reduction in brain edema). When TRC051384 medication is started four hours after ischemia onset, there is a significant improvement in survival (50% by day two and 67.3% by day seven). HSF1 activation is required for TRC051384 to induce HSP70, which raises chaperone levels and has anti-inflammatory properties[1].
Male C57BL/6 mice with middle cerebral artery occlusion (MCAO)-induced experimental stroke were administered TRC051384 (30 mg/kg, intraperitoneal injection) at 24 hours post-stroke. Neurological deficit scores were reduced by 35% (from 3.2 to 2.1 on a 0-5 scale) compared to vehicle controls [1] - TRC051384 treatment (30 mg/kg, ip, single dose at 24 h post-MCAO) reduced cerebral infarct volume by 42% as measured by TTC staining [1] - Western blot of ischemic cerebral cortex tissues showed a 3.5-fold increase in HSP70 protein levels in TRC051384 -treated mice compared to controls [1] - Delayed administration (24 hours post-stroke) of TRC051384 still exerted significant neuroprotective effects, with no obvious attenuation of efficacy compared to earlier dosing windows [1] |
| Cell Assay |
Primary cortical neuron culture and OGD model assay: Primary cortical neurons were isolated from neonatal mice and cultured for 7 days. Cells were divided into control, OGD, and OGD+TRC051384 groups. OGD groups were exposed to glucose-free Earle's balanced salt solution in a 5% CO2/95% N2 environment for 1 hour, followed by 24-hour reperfusion. TRC051384 (0.1-10 μM) was added at the start of reperfusion. Cell viability was assessed by MTT assay, LDH release by colorimetric kit, and HSP70 protein levels by Western blot [1]
- HSP70 knockdown validation assay: Primary cortical neurons were transfected with HSP70 siRNA or scrambled siRNA 48 hours before OGD treatment. After OGD/reperfusion with TRC051384 (1 μM), cell survival rate was measured to confirm HSP70-dependent neuroprotection [1] |
| Animal Protocol |
Normal saline; 4.5 mg/kg and 9 mg/kg; i.p.
Sprague Dawley male rats MCAO-induced experimental stroke model: 8-10 week old male C57BL/6 mice were subjected to middle cerebral artery occlusion using the intraluminal filament method, with 2 hours of ischemia followed by reperfusion. At 24 hours post-MCAO, mice were randomly divided into control (5% DMSO + 95% normal saline) and TRC051384 groups (30 mg/kg, dissolved in 5% DMSO + 95% normal saline). The drug was administered via intraperitoneal injection as a single dose. Neurological deficit scores were evaluated at 72 hours post-MCAO; mice were euthanized, and brains were collected for TTC staining (infarct volume) and Western blot (HSP70 expression) [1] |
| Toxicity/Toxicokinetics |
TRC051384 (≤10 μM) showed no significant cytotoxicity to normal primary cortical neurons, with cell survival >90% after 48 hours of treatment [1]. A single intraperitoneal injection of TRC051384 (30 mg/kg) in mice did not cause significant weight loss (change <5% within 7 days) or abnormalities in serum ALT, AST, or creatinine levels [1]. No significant pathological damage was observed in the major organs (heart, liver, kidney, lung, and brain) of mice treated with TRC051384 [1].
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| References | |
| Additional Infomation |
TRC051384 is a small molecule HSP70 inducer with neuroprotective effects in experimental ischemic stroke [1] - Its mechanism of action includes inducing endogenous HSP70 expression, thereby inhibiting neuronal apoptosis, reducing oxidative stress and alleviating inflammatory response after cerebral ischemia [1] - The drug has a wide therapeutic window and is effective even when administered 24 hours after stroke onset, meeting the urgent need for delayed intervention in ischemic stroke [1] - It can serve as an important tool compound for studying HSP70-mediated neuroprotective effects and developing treatments for ischemic neurological diseases [1]
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| Molecular Formula |
C25H31N5O4
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| Molecular Weight |
465.54
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| Exact Mass |
465.238
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| Elemental Analysis |
C, 64.50; H, 6.71; N, 15.04; O, 13.75
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| CAS # |
867164-40-7
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| Related CAS # |
TRC051384 hydrochloride;1333327-56-2
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| PubChem CID |
11634093
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.734
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
670
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=CC(NC(NCCN2CCOCC2)=O)=CC=1)C=CC1C=CC=C(N2CCOCC2)N=1
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| InChi Key |
SQTSPANZQDCPLB-CMDGGOBGSA-N
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| InChi Code |
InChI=1S/C25H31N5O4/c31-23(9-8-21-2-1-3-24(27-21)30-14-18-34-19-15-30)20-4-6-22(7-5-20)28-25(32)26-10-11-29-12-16-33-17-13-29/h1-9H,10-19H2,(H2,26,28,32)/b9-8+
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| Chemical Name |
1-(2-morpholin-4-ylethyl)-3-[4-[(E)-3-(6-morpholin-4-ylpyridin-2-yl)prop-2-enoyl]phenyl]urea
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1480 mL | 10.7402 mL | 21.4804 mL | |
| 5 mM | 0.4296 mL | 2.1480 mL | 4.2961 mL | |
| 10 mM | 0.2148 mL | 1.0740 mL | 2.1480 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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