Structure of GV-58
CAS No.: 1402821-41-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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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 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P305+P351+P338 |
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].
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In Vitro:
Cell Line
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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 |
Tags: GV-58 | GV58 | GV 58 | Calcium Channel | Ca2+ channels | Ca channels | lambert-eaton myasthenic syndrome | LEMS | upper arm muscle | inhibitor | 1402821-41-3 |
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