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Chemical Structure| 1402821-41-3 Chemical Structure| 1402821-41-3

Structure of GV-58
CAS No.: 1402821-41-3

Chemical Structure| 1402821-41-3

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GV-58 is a potent, selective N- and P/Q-type Ca2+ channels agonist with EC50 of 7.21/8.81 μM for N-type/P-Q-type Ca2+ channel and 20-fold less potent CDK inhibitor activity.

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Product Details of GV-58

CAS No. :1402821-41-3
Formula : C18H26N6OS
M.W : 374.50
SMILES Code : CC[C@@H](NC1=NC(NCC2=CC=C(C)S2)=C3N=CN(CCC)C3=N1)CO
MDL No. :MFCD28385865
InChI Key :DPTXJOUVBMUSGY-CYBMUJFWSA-N
Pubchem ID :71463101

Safety of GV-58

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P305+P351+P338

Isoform Comparison

Biological Activity

Description
GV-58, a new agonist for N- and P/Q-type calcium (Ca2+) channels, has EC50 values of 7.21 and 8.81 μM, respectively. It decelerates channel deactivation, leading to significantly enhanced presynaptic Ca2+ influx upon activation. GV-58 is applicable in research on Lambert-Eaton myasthenic syndrome (LEMS)[1][2][3].

In Vitro:

Cell Line
Concentration Treated Time Description References
tsA-201 cells 50 μM To evaluate the agonist effect of GV-58 on P/Q-type calcium channels, results showed GV-58 significantly increased Ca2+ channel tail current at 50 μM. J Physiol. 2014 Aug 15;592(16):3687-96
SH-SY5Y cells 50 μM 24 hours To evaluate the effect of GV-58 on cell survival under physiological ATP conditions, results showed GV-58 did not affect cell survival at 50 μM. J Physiol. 2014 Aug 15;592(16):3687-96
tsA-201 cells 8.81 µM GV-58 showed significant agonist effects on P/Q-type calcium channels J Neurosci. 2013 Jun 19;33(25):10559-67
tsA-201 cells 7.21 µM GV-58 showed significant agonist effects on N-type and P/Q-type calcium channels but no effect on L-type calcium channels J Neurosci. 2013 Jun 19;33(25):10559-67
mouse ventral horn neurons 20 μM 30 minutes GV-58 significantly increased the mean firing rate but had no significant effect on the mean burst rate Front Cell Neurosci. 2017 Sep 29;11:304
NSC-34 motor neuron-like cells 3 μM GV-58 increased the amplitude of INa and reduced current inactivation in NSC-34 cells. Biomedicines. 2022 Mar 20;10(3):721
Pituitary GH3 cells 0.3-100 μM 1 minute GV-58 enhanced the transient and late components of voltage-gated Na+ current (INa) in GH3 cells, with EC50 values for peak and late INa being 8.9 and 2.6 μM, respectively. Biomedicines. 2022 Mar 20;10(3):721
tsA-201 cells 12.5 µM GV-58 partially restored Ca2+ current by shifting mutant activation to more hyperpolarizing potentials and slowing deactivation. Consequently, GV-58 also rescued a portion of Ca2+ flux during action potential–like stimuli. J Gen Physiol. 2019 Jun 3;151(6):850-859
SH-SY5Y cells 0.1-100 μM 24 hours To evaluate the effects of GV-58 and its analogs on cell survival. Results showed that GV-58 at 100 μM concentration only reduced cell survival by 8%, while MF-06 significantly reduced cell survival at concentrations of 10 μM and above. Neuropharmacology. 2018 Mar 15;131:176-189
HEK293 cells 1-100 μM 15-30 seconds To evaluate the agonist gating modification effects of GV-58 and its analogs on Cav2.1 voltage-gated calcium channels. Results showed that GV-58 and its analogs significantly prolonged the deactivation time constant of calcium channels, increasing calcium ion influx. Neuropharmacology. 2018 Mar 15;131:176-189

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
CFW mice LEMS passive transfer model Ex vivo nerve-muscle preparation 50 μM GV-58 + 1.5 μM 3,4-DAP 30-60 minutes incubation To evaluate the effect of GV-58 combined with 3,4-DAP on neurotransmitter release at LEMS model NMJs, results showed the combination completely restored the magnitude of neurotransmitter release. J Physiol. 2014 Aug 15;592(16):3687-96
Mice Neuromuscular junction model In vitro culture 50 μM 30 minutes To evaluate the effects of GV-58 on synaptic transmission in the neuromuscular junction model. Results showed that 50 μM GV-58 significantly increased transmitter release by more than two-fold. Neuropharmacology. 2018 Mar 15;131:176-189
CFW mice LEMS passive transfer mouse model Ex vivo nerve-muscle preparation 50 µM 30 minutes GV-58 significantly enhanced neurotransmitter release at LEMS model neuromuscular junctions J Neurosci. 2013 Jun 19;33(25):10559-67
Goat Isolated caprine detrusor strips In vitro organ bath 6.8 μM Single administration, exposure time not specified To investigate the reversal effect of GV-58 on the inhibition of KCl-induced detrusor contractility by 40 μM cilnidipine. Results showed that GV-58 significantly reversed the inhibitory effect of cilnidipine. Curr Ther Res Clin Exp. 2023 Sep 30;99:100717
Larval Drosophila and crayfish Neuromuscular junction models Dissolved in saline 0.1 mM and 1.0 mM GV-58 did not produce any consistent alteration in synaptic transmission at the larval Drosophila and crayfish neuromuscular junctions MicroPubl Biol. 2024 Dec 23;2024:10

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.67mL

0.53mL

0.27mL

13.35mL

2.67mL

1.34mL

26.70mL

5.34mL

2.67mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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