2. Membrane Transporter/Ion Channel Neuronal Signaling
  3. TRP Channel
  4. JW-65

JW-65 is a selective TRPC3 channel inhibitor with favorable blood-brain barrier penetration. JW-65 directly binds to human TRPC3 protein and modulates calcium signaling to reduce seizure susceptibility. JW-65 reduces seizure incidence, severity, and duration while prolonging seizure latency in multiple seizure models. JW-65 alleviates Aβ‑induced neuronal damage. JW-65 serves as a valuable tool for research on epilepsy, seizure disorders, and Alzheimer’s disease.

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JW-65

JW-65 Chemical Structure

CAS No. : 2763378-71-6

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Based on 1 publication(s) in Google Scholar

JW-65 Related Antibodies

Top Publications Citing Use of Products

View All TRP Channel Isoform Specific Products:

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TRPA1 TRPC3 TRPC4 TRPC5 TRPC6 TRPC7 TRPM8 TRPM2 TRPM3 TRPM4 TRPM7 TRPML1 TRPML2 TRPML3 TRPV1 TRPV2 TRPV3 TRPV4 TRPV6

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Description

JW-65 is a selective TRPC3 channel inhibitor with favorable blood-brain barrier penetration. JW-65 directly binds to human TRPC3 protein and modulates calcium signaling to reduce seizure susceptibility. JW-65 reduces seizure incidence, severity, and duration while prolonging seizure latency in multiple seizure models. JW-65 alleviates Aβ‑induced neuronal damage. JW-65 serves as a valuable tool for research on epilepsy, seizure disorders, and Alzheimer’s disease[1][2][3].

IC50 & Target[1]

TRPC3

0.37 μM (IC50)

In Vitro

JW-65 (0.001-10 μM) potently inhibits hTRPC3-mediated currents in HEK293 cells, with IC50 values of 0.37 μM (no extracellular Ca2+)[2].
JW-65 (10 μM) is a selective inhibitor of hTRPC3 over other TRP channel family members, showing no inhibition of hTRPA1, rTRPV1, rTRPV4, or hTRPM8, and only partial inhibition of closely related hTRPC6 (39%) and hTRPC7 (26%) at 10 μM[2].
JW-65 exhibits significantly improved metabolic stability over Pyr3 (HY-108465), with a half-life of more than 4 hours in mouse, rat, and human liver microsomes[2][3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

JW-65 Related Antibodies
Parmacokinetics
Species Dose Route Cmax Tmax T1/2
Mice[3] 100 mg/kg i.p. 156 ng/mL 0.33 h 3.1 h
In Vivo

JW-65 (5-40 mg/kg; i.p.; single dose) dose-dependently reduces acoustically-evoked seizure incidence, latency, duration, and severity in male and female GEPR-3 rats, with females exhibiting greater sensitivity[1].
JW-65 (10 mg/kg; i.p.; daily; 5 consecutive days) completely suppress acoustically-evoked seizures in male and female GEPR-3 rats[1].
Pretreatment with JW-65 (100 mg/kg; i.p.; once daily for 2 consecutive days, plus a third dose on experiment day 15 minutes before Pilocarpine (HY-B0726A) injection) substantially impairs the initiation and development of Pilocarpine-induced status epilepticus in mice[3].
Post-seizure onset treatment with JW-65 (100 mg/kg; i.p.; single dose administered after Stage 2 seizure onset) mitigates the progression of Pilocarpine-induced status epilepticus in mice, preventing all treated mice from developing long-lasting status epilepticus and reducing electrographic seizure activity[3].
JW-65 (20-100 mg/kg; i.p.; single dose 30 minutes before PTZ injection) reduces susceptibility to PTZ-induced seizures in mice in a dose-dependent manner[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Genetically Epilepsy-Prone Rats (GEPR-3) (adult male and female, 8 weeks old)[1]
Dosage: 5 mg/kg; 10 mg/kg; 20 mg/kg; 40 mg/kg
Administration: i.p.; single dose
Result: Reduced seizure duration in males at 5 mg/kg without altering other seizure parameters in either sex.
Dose-dependently decreased WRS and GTCS incidence, prolonged latency, shortened duration, and reduced severity at 10, 20, and 40 mg/kg in both sexes, with stronger effects in females.
Impaired seizure activity most potently at 40 mg/kg, with maximal inhibition of GTCS (89%) in females.
Induced mild neurological side effects only at 40 mg/kg, and was well-tolerated at 5-20 mg/kg.
Animal Model: Genetically Epilepsy-Prone Rats (GEPR-3) (adult male and female, 8 weeks old)[1]
Dosage: 10 mg/kg
Administration: i.p.; daily; 5 consecutive days
Result: Completely suppressed WRS and GTCS incidence, duration, and severity in both sexes at 0.5-4 h after the last treatment; seizure susceptibility recovered to baseline at 24 h.
Markedly prolonged seizure latency in both sexes at 0.5-4 h after the last treatment.
Significantly reduced seizure duration in females but not males at 24 h after the last treatment.
Animal Model: C57BL/6 (young adult male, 8-10 weeks, pilocarpine-induced status epilepticus, pretreated with methylscopolamine and terbutaline prior to pilocarpine injection)[3]
Dosage: 100 mg/kg
Administration: i.p.; once daily for 2 consecutive days, plus a third dose on experiment day 15 minutes before pilocarpine injection
Result: Markedly reduced overall behavioral seizure scores.
Prolonged latencies to Stage 2, 3, and 4 seizures with high statistical significance.
Decreased both average and maximal seizure scores.
Dramatically lowered the incidence of status epilepticus.
Animal Model: C57BL/6 (young adult male, 8-10 weeks, pilocarpine-induced status epilepticus, pretreated with methylscopolamine and terbutaline prior to pilocarpine injection, treatment administered after seizure onset)[3]
Dosage: 100 mg/kg
Administration: i.p.; single dose administered after Stage 2 seizure onset
Result: Reduced overall behavioral seizure scores.
Prolonged latencies to Stage 3 and Stage 4 seizures significantly.
Lowered both average and maximal seizure scores.
Blocked long-lasting status epilepticus in all treated mice.
Elevated survival rate to 88.8% from 53.8% in vehicle controls.
Decreased EEG spike counts time-dependently within 4 hours.
Animal Model: C57BL/6 (young adult male, 8-10 weeks, pentylenetetrazole-induced seizures)[3]
Dosage: 20 mg/kg; 100 mg/kg
Administration: i.p.; single dose 30 minutes before PTZ injection
Result: Lowered the proportion of mice exhibiting myoclonic jerks (MJ) and prolonged MJ latency at 20 mg/kg.
Reduced the incidence of both MJ and GTCS in mice at 100 mg/kg.
Markedly delayed the onset of initial MJ and GTCS at 100 mg/kg, with efficacy similar to phenytoin.
Molecular Weight

445.22

Formula

C18H13Cl2F3N4O2
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

FC(C1=C(C(NCC)=O)C=NN1C2=CC=C(C=C2)N(C=CC(Cl)=C3Cl)C3=O)(F)F
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 25 mg/mL (56.15 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.2461 mL 11.2304 mL 22.4608 mL
5 mM 0.4492 mL 2.2461 mL 4.4922 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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In Vivo Dissolution Calculator
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Working solution concentration: mg/mL
Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.2461 mL 11.2304 mL 22.4608 mL 56.1520 mL
5 mM 0.4492 mL 2.2461 mL 4.4922 mL 11.2304 mL
10 mM 0.2246 mL 1.1230 mL 2.2461 mL 5.6152 mL
15 mM 0.1497 mL 0.7487 mL 1.4974 mL 3.7435 mL
20 mM 0.1123 mL 0.5615 mL 1.1230 mL 2.8076 mL
25 mM 0.0898 mL 0.4492 mL 0.8984 mL 2.2461 mL
30 mM 0.0749 mL 0.3743 mL 0.7487 mL 1.8717 mL
40 mM 0.0562 mL 0.2808 mL 0.5615 mL 1.4038 mL
50 mM 0.0449 mL 0.2246 mL 0.4492 mL 1.1230 mL
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JW-65 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

JW-652763378-71-6JW65JW 65TRP ChannelTransient receptor potential channelsAlzheimer’s diseasecalcium signalingGEPR-3 ratshTRPC3 proteinepilepsyTRPC3 channelHEK293 cellsseizuresstatus epilepticusmiceInhibitorinhibitorinhibit

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