BRF110
BRF110 is an orally active, blood-brain barrier-penetrant Nurr1-RXRα heterodimer activator with an EC50 of 0.9 μM in human systems. BRF110 increases the mRNA level of BDNF, upregulates the transcription of TH, AADC and GCH1 to elevate striatal dopamine levels. BRF110 exhibits neuroprotective activity against MPP+-induced cytotoxicity. BRF110 prevents dopaminergic neuron death, protects nerve cells from toxic damage, and improves motor coordination in mouse models. BRF110 can be used in research related to Parkinson's disease.
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- CAS 番号: 2095489-35-1
- 分子式: C22H18F3N3O2
- 分子量:413.39
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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生物活性
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化学情報
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Nuclear Hormone Receptor 4A/NR4A アイソフォーム固有の製品をすべて表示
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生物活性
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Nurr1-RXRα 0.9 μM (EC50) |
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Cell Line
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Type | Value | Description | References |
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| SH-SY5Y | EC50 |
0.9 μM
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Activation of Nurr1-RXRα heterodimer in human SH-SY5Y neuroblastoma cells assessed via DR5-tk promoter-driven luciferase reporter assay, normalized to β-galactosidase activity after overnight incubation.
Activation of Nurr1-RXRα heterodimer in human SH-SY5Y neuroblastoma cells assessed via DR5-tk promoter-driven luciferase reporter assay, normalized to β-galactosidase activity after overnight incubation.
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39945195 |
BRF110 (2-12.5 μM; 24 h) protects SHSY-5Y cells against H2O2- and MPP+-induced cell death in a Nurr1-dependent manner[2].
BRF110 (0.5-12.5 μM; overnight) activates the Nurr1-RXRα heterodimer in human SH-SY5Y neuroblastoma cells, with an EC50 of 0.9 μM[1].
BRF110 (0.5-12.5 μM; 12 h) exhibits much higher selectivity for the Nurr1-RXRα heterodimer than for other RXRα heterodimers and homodimers in human SH-SY5Y neuroblastoma cells, and only partially activates the Nur77-RXRα heterodimer[1].
BRF110 (12.5 μM) protects mouse Neuro-2a neuroblastoma cells against MPP+-induced toxicity, with an efficacy of 52.5% at the concentration of 12.5 μM[1].
BRF110 (12.5 μM; 0-9 h) transiently induces BDNF expression in human SH-SY5Y neuroblastoma cells via a Nurr1-dependent mechanism, in which Nurr1 and RXRα directly bind to BDNF promoter IV[1].
BRF110 (0.5, 12.5 μM; 24 h) only induces a slight upregulation of SREBP-1c expression by approximately 5-fold in human HepG2 hepatocytes at the concentration of 12.5 μM[1].
BRF110 (12.5 μM) upregulates the expression of key dopamine (DA) biosynthesis genes (TH, AADC, GCH1) in SHSY-5Y cells by activating Nurr1:RXRα[2].
BRF110 (12.5 μM; 24 h, 14 d) protects human induced pluripotent stem cell (iPSC)-derived dopaminergic (DAergic) neurons against MPP+-induced death and restores impaired neurite morphology in LRRK2G2019S dopaminergic neurons derived from patients with Parkinson's disease (PD)[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human SH-SY5Y neuroblastoma cells
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Concentration:12.5 μM
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Incubation Time:0, 1, 2, 4.5, 6, 7.5, 9 h (time-course analysis); 2 h (ChIP-PCR)
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Result:Induced a transient ~1.8-fold increase in BDNF mRNA expression, peaking at 2 h and returning to baseline within 5 h.
Promoted binding of both Nurr1 and RXRα to BDNF promoter IV (but not promoters I, II, or III) 2 h after treatment.
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Cell Line:human HepG2 hepatic cells
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Concentration:0.5, 12.5 μM
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Incubation Time:24 h
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Result:Triggered a small concentration-dependent increase in SREBP-1c expression, reaching a maximum of ~5-fold over controls at 12.5 μM.
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Cell Line:human DAergic neuroblastoma SHSY-5Y cells
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Concentration:2 μM; 12.5 μM (incubation with MPP+); 12.5 μM (incubation with H2O2)
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Incubation Time:24 h (incubation with MPP+)
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Result:Increased cell survival against H2O2 and MPP+ in a dose-dependent manner.
Showed no effect on cell differentiation or proliferation.
Lost protective effect against MPP+ in cells with Nurr1 knockdown.
BRF110 (15 mg/kg; p.o.; single administration) increases the level of BDNF mRNA in mouse brains by approximately 25%[1].
BRF110 (10 mg/kg; i.p.; once every 12 hours; for 6 consecutive days) exerts neuroprotective effects against acute MPTP (HY-W114750)-induced Parkinson's disease in C57BL/6 mice, increasing the survival rate of TH (+) midbrain neurons by 31%, doubling the retention rate of striatal axon terminals, and improving motor coordination by more than 100%[2].
The neuroprotective effect of BRF110 (10 mg/kg, i.p., once every 12 hours for 6 days) against MPTP-induced Parkinson's disease in 129SV mice depends on functional Nurr1: it increases the survival rate of TH (+) midbrain neurons in wild-type mice, but shows no effect in Nurr1+− mice[2].
BRF110 (10 mg/kg; i.p.; once every 12 hours for 14 consecutive days) exerts potent neuroprotective effects in a unilateral 6-OHDA (HY-B1081)-induced Parkinson's disease model in C57BL/6 mice, increasing the survival rate of TH (+) midbrain neurons by 47%, restoring motor coordination, reducing contralateral rotation counts by 8-fold, and increasing the retention rate of striatal axonal projections by 10-fold[2].
BRF110 (10 mg/kg; i.p.; once every 12 hours; for 14 consecutive days) exerts neuroprotective effects in the AAV-ASYN hereditary Parkinson's disease model of C57BL/6 mice, increasing the survival rate of TH (+) midbrain neurons by approximately 47% and enhancing the retention rate of striatal axonal projections by more than 5-fold[2].
BRF110 (10 mg/kg; i.p.; single administration) increases the expression level of TH in the midbrain, as well as the levels of DA and its metabolites in the striatum, in both wild-type and ASYN transgenic mice, without altering the norepinephrine level[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:mice[1]
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Dosage:15 mg/kg
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Administration:p.o.; single dose
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Result:Increased BDNF mRNA levels in the brainstem midline by ~25% compared to vehicle controls.
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Animal Model:mice[1]
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Dosage:10 mg/kg (i.p.); 14 mg/kg (p.o.)
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Administration:i.p.; daily; 5 days; p.o.; daily; 4 days
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Result:Did not elevate triglyceride levels with intraperitoneal administration, resulting in a modest ~25% decrease compared to vehicle-treated animals.
Did not cause statistically significant changes in triglyceride levels between pre-treatment and post-treatment measurements with oral administration.
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Animal Model:C57BL/6 (acute MPTP-induced Parkinson's disease model)[2]
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Dosage:10 mg/kg
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Administration:i.p.; every 12 h; 6 d
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Result:Improved motor coordination by over 100% as measured by the accelerating rotarod test.
Increased TH(+) midbrain neuron survival per side by 31% compared with vehicle-treated MPTP mice.
Doubled the number of remaining striatal TH(+) axonal terminals compared with vehicle-treated MPTP mice.
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Animal Model:129SV wild-type; 129SV Nurr1+/− heterozygous (acute MPTP-induced Parkinson's disease model)[2]
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Dosage:10 mg/kg
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Administration:i.p.; every 12 h; 6 d
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Result:In wild-type 129SV mice, increased TH(+) midbrain neuron survival per side from 2,500 to 3,250 compared with vehicle-treated MPTP mice.
Neuroprotective effects were abolished in Nurr1+/− heterozygous mice.
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Animal Model:C57BL/6 (unilateral 6-hydroxydopamine-induced Parkinson's disease model)[2]
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Dosage:10 mg/kg
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Administration:i.p.; every 12 h; 14 d
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Result:Reduced non-selective dopamine receptor agonist-induced contralateral turns by approximately eightfold compared with vehicle-treated 6-OHDA mice.
Restored motor coordination to near control levels as measured by the accelerating rotarod test.
Increased TH(+) midbrain neuron survival by 47% compared with vehicle-treated 6-OHDA mice.
Increased preservation of striatal TH(+) axonal projections by 10-fold compared with vehicle-treated 6-OHDA mice.
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Animal Model:C57BL/6 (unilateral AAV-mediated α-synuclein overexpression Parkinson's disease model)[2]
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Dosage:10 mg/kg
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Administration:i.p.; every 12 h; 14 d
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Result:Increased TH(+) midbrain neuron survival by ~47% compared with vehicle-treated AAV-ASYN mice.
Increased striatal TH(+) axonal projections by more than fivefold compared with vehicle-treated AAV-ASYN mice.
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Animal Model:Wild-type; α-synuclein transgenic[2]
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Dosage:10 mg/kg
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Administration:i.p.; single dose
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Result:In wild-type mice, increased midbrain TH gene expression and elevated striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) levels, with unchanged noradrenaline levels.
In ASYN transgenic mice, increased striatal DA, DOPAC, and HVA levels, with unchanged noradrenaline levels.
化学情報
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CAS 番号 2095489-35-1
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分子量 413.39
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分子式 C22H18F3N3O2
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SMILES
O=C(O)C1=CC=C(N(C)C2=NC(C3=CC=CC=C3)=NC(C(F)(F)F)=C2CC=C)C=C1
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
BRF110 関連分類
HY-138967 関連分類
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