Drofenine
Based on 1 publication(s) in Google Scholar
Drofenine (Cycloadiphene; Hexahydroadiphenine) is an brain-penetrant antispasmodic agent. Drofenine is a Kv2.1 channel inhibitor with human IC50 of 9.53 μM. Drofenine is a butyrylcholinesterase (BChE) inhibitor with Ki of 0.003 mM, and is a TRPV3 activator. Drofenine blocks Kv2.1-dependent potassium efflux, inhibits Kv2.1/JNK/NF-κB and IkBa/NF-kB signaling, suppresses Kv2.1 mRNA/protein expression. Drofenine suppresses oligomeric Aβ-induced microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation, improves cognitive impairment, promotes neurite outgrowth. Drofenine induces calcium influx in keratinocytes and exert cytotoxicity against keratinocytes. Drofenine ameliorates diabetic peripheral neuropathy -like pathology. Drofenine can be used for the researches of Alzheimer's disease, diabetic peripheral neuropathy and smooth muscle spasm.
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- CAS No.: 1679-76-1
- Formule: C20H31NO2
- Masse moléculaire:317.47
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Activité biologique
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Publications Citing Use of MedChemExpress (MCE) Drofenine
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Activité biologique
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KV2.1 9.53 μM () |
BChE 3 μM () |
TRPV3 |
NLRP3 |
Drofenine (10 μM; 0.5 h) suppresses oligomeric Aβ (o-Aβ)-enhanced Kv2.1-dependent outward potassium current and density in CHO-Kv2.1 cells by blocking o-Aβ-induced delays in Kv2.1 channel inactivation[1].
Drofenine (5-20 μM; 30 min) inhibits membrane potential in CHO-Kv2.1 cells without affecting normal CHO cells[2].
Drofenine (5-20 μM) does not reduce the viability of CHO-Kv2.1 cells[2].
Drofenine (1-10 μM) potently inhibits Kv2.1 channel currents in CHO-Kv2.1 cells with an IC50 of 9.53 μM[2].
Drofenine (1-10 μM) shows minimal inhibition of Kv2.2 channel currents in CHO-Kv2.2 cells at concentrations that effectively inhibit Kv2.1, indicating selectivity for Kv2.1[2].
Drofenine (0.01-0.1 mM) acts as a pure competitive inhibitor of purified human serum butyrylcholinesterase, with a Ki value of 0.003 mM[3].
Drofenine (30-1000 μM) acts as a selective agonist of human TRPV3 in TRPV3-overexpressing HEK-293 cells, activating calcium flux with an EC50 of 207 μM without activating TRPA1, TRPM8, TRPV1, TRPV2, or TRPV4 at concentrations up to 1000 μM[4].
Drofenine (30-1000 μM) acts as a potent agonist of endogenous TRPV3 in HaCaT human keratinocytes, inducing calcium flux with an EC50 of 605 μM[4].
Drofenine (10-1000 μM; 24 h) is cytotoxic to HaCaT human keratinocytes after 24 h of incubation, with an LC50 of 230 μM[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human immortalized keratinocyte (HaCaT) cells
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Concentration:10-1000 μM
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Incubation Time:24 h
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Result:Was more cytotoxic to HaCaT cells than 2-APB and carvacrol, with an LC50 of 230 μM, compared to LC50 values of >300 μmol/L for both 2-APB (HY-W009724) and carvacrol (HY-N0711).
Drofenine (10-20 mg/kg; 4 total doses; Weeks 7, 8, 9, 10 post-STZ injection) suppresses Kv2.1 expression and function in DRG tissue, promotes DRG neuron neurite outgrowth, and ameliorates motor and sensory deficits in STZ (HY-13753)-induced type 1 DPN mice via Kv2.1 inhibition[2].
Drofenine (10-20 mg/kg; 4 total doses; Weeks 1, 2, 3, 4 of study period) suppresses Kv2.1 expression and function in DRG tissue, promotes DRG neuron neurite outgrowth, and ameliorates motor and sensory deficits in spontaneous type 2 db/db DPN mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:5xFAD transgenic (APPSwFlLon, PSEN1-M146L-L286V) (female, 7 months old at treatment start, Alzheimer's disease model); wild-type (WT) (female)[1]
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Dosage:10 mg/kg/day
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Administration:i.p.; daily; 8 weeks
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Result:Improved short-term working memory via increased discrimination index in novel object recognition test.
Improved spatial working memory via increased number of novel arm crossings in Y-maze test.
Improved spatial learning and long-term memory via reduced escape latency in Morris water maze training trials and increased platform crossing frequency in Morris water maze probe trials in 5xFAD mice; no cognitive improvement observed in Kv2.1-knockdown 5xFAD mice.
Reduced Iba1-positive microglial and GFAP-positive astrocytic gliosis in 5xFAD mouse brains.
Reduced NLRP3-ASC positive puncta, and reduced protein levels of NLRP3, p-NLRP3, ASC, Cas1 (p20), IL-1β, p-JNK, and p-NF-κB in 5xFAD mice.
Reduced microglial NF-κB nuclear translocation in 5xFAD mice; no anti-inflammatory effects observed in Kv2.1-knockdown 5xFAD mice.
Reduced AT8-positive hyperphosphorylated Tau (Ser202/Thr205) areas in the hippocampus of 5xFAD mice.
Reduced protein levels of p396-Tau, p231-Tau, p199-Tau, p-GSK3β, and p-CaMKII-α in 5xFAD mice; no effects on Tau phosphorylation or related kinases observed in Kv2.1-knockdown 5xFAD mice.
Improved long-term potentiation induction and maintenance in the hippocampal DG region of 5xFAD mice.
Restored protein levels of synaptic markers PSD95, synaptophysin (SYN), and VAMP2 in 5xFAD mice; no synaptic improvement observed in Kv2.1-knockdown 5xFAD mice.
Reduced TUNEL-positive apoptotic neurons in 5xFAD mice.
Reversed loosely arranged neuronal nuclei (Nissl staining) in the hippocampus of 5xFAD mice; no effects on neuronal survival observed in Kv2.1-knockdown 5xFAD mice.
Showed no significant hepatotoxicity or nephrotoxicity via no changes in serum ALT, AST, or urea levels in treated WT or 5xFAD mice.
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Animal Model:C57BL/6 (male, 7 weeks old at study initiation, streptozotocin-induced type 1 diabetes)[2]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:4 total doses; Weeks 7, 8, 9, 10 post-STZ injection
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Result:Lowered Kv2.1/T-ERK ratios relative to vehicle-treated STZ mice.
Decreased relative Kv2.1 area in DRG tissue compared to vehicle-treated STZ mice.
Lowered relative Kv2.1 mRNA levels compared to vehicle-treated STZ mice.
Reduced elevated potassium currents in STZ mouse DRG neurons.
Increased total neurite length relative to vehicle-treated STZ mice.
Improved motor nerve conduction velocity relative to vehicle-treated STZ mice.
Reduced sensitivity to mechanical stimuli relative to vehicle-treated STZ mice.
Normalized thermal response relative to vehicle-treated STZ mice.
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Animal Model:BKS Cg-m+/+Leprdb/J (db/db) (male, 17 weeks old at study initiation, spontaneous type 2 diabetes)[2]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:4 total doses; Weeks 1, 2, 3, 4 of study period
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Result:Lowered Kv2.1/T-ERK ratios relative to vehicle-treated db/db mice.
Decreased relative Kv2.1 area in DRG tissue compared to vehicle-treated db/db mice.
Lowered relative Kv2.1 mRNA levels compared to vehicle-treated db/db mice.
Reduced elevated potassium currents at +50 mV in db/db mouse DRG neurons.
Increased total neurite length relative to vehicle-treated db/db mice.
Improved motor nerve conduction velocity relative to vehicle-treated db/db mice.
Reduced sensitivity to mechanical stimuli relative to vehicle-treated db/db mice.
Normalized thermal response relative to vehicle-treated db/db mice.
Chemical Information
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CAS No. 1679-76-1
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Masse moléculaire 317.47
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Formule C20H31NO2
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SMILES
O=C(OCCN(CC)CC)C(C1CCCCC1)C2=CC=CC=C2
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Synonyms
Cycloadiphene; Hexahydroadiphenine
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (1)
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Journal Impact Factor
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Most Recent
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Biochem Biophys Res Commun
Inhibition of the transient receptor potential vanilloid 3 channel attenuates carbon tetrachloride-induced hepatic fibrosis. [Abstract]2021 Jun 18:558:86-93. PMID: 33906111
Pureté et documentation
Références
[1]. Lu J, et al. Drofenine as a Kv2.1 inhibitor alleviated AD-like pathology in mice through Aβ/Kv2.1/microglial NLRP3/neuronal Tau axis. Acta Pharm Sin B. 2025;15(1):371-391. [Content Brief]
[2]. Xu X, et al. Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice. iScience. 2020;23(10):101617. Published 2020 Sep 28. [Content Brief]
[3]. Bodur E, et al. Inhibition effects of benactyzine and drofenine on human serum butyrylcholinesterase. Arch Biochem Biophys. 2001;386(1):25-29. [Content Brief]
[4]. Deering‐Rice C E, et al. Drofenine: a 2‐APB analog with improved selectivity for human TRPV3[J]. Pharmacology research & perspectives, 2014, 2(5): e00062. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Drofenine Related Classifications
HY-B1239A Related Classifications
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- Drofenine
- 1679-76-1
- Cycloadiphene
- Hexahydroadiphenine
- Potassium Channel
- Cholinesterase (ChE)
- TRP Channel
- NOD-like Receptor (NLR)
- Amyloid-β
- Tau Protein
- JNK
- NF-κB
- IKK
- NLRP3 inflammasome
- TRPV3
- human serum butyrylcholinesterase
- 5xFAD Alzheimer's disease mice
- Kv2.1 channel
- M1/M2 muscarinic receptors
- Tau hyperphosphorylation
- HEK-293 cells
- HaCaT human keratinocytes
- CHO-Kv2.1 cells
- Inhibitor
- inhibitor
- inhibit