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BioAssay: AID 504584

Inhibitors of T-Type Calcium Channels (Ancillary Pharm)

T-type Ca2+ channels are also called low voltage-activated channels because they open at voltages near the resting membrane potential of most cells. In many types of neurons, Ca2+ influx through T-type channels triggers low-threshold spikes, which in turn trigger a burst of action potentials mediated by Na+ channels (1). Burst firing is thought to play an important role in the synchronized more ..
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 Related BioAssays
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AID: 504584
Data Source: Vanderbilt Screening Center for GPCRs, Ion Channels and Transporters (T type (Ancillary Binding Assay))
Depositor Category: NIH Molecular Libraries Screening Center Network
Deposit Date: 2011-03-26

Data Table ( Complete ):           All
Tested Compound:
Depositor Specified Assays
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AIDNameTypeComment
463087Inhibitors of Cav3 T-type Calcium Channelssummary
449739Inhibitors of Cav3 T-type Calcium Channels: Primary Screenscreening
489005Inhibitors of T-Type Calcium Channelconfirmatory
493021Inhibitors of T-Type Calcium Channelsconfirmatory
493022Inhibitors of T-Type Calcium Channels (SynthLib1)confirmatory
493023Inhibitors of T-Type Calcium Channels (SynthLib2)confirmatory
493041Inhibitors of T-Type Calcium Channels (SynthLib3)confirmatory
504425Mode of action assay-Specificity dose response assay for the identification of selective inhibitors of T-type calcium subunit Cav3.2 in the Cav3.3 expressing cell line on automated patch clampconfirmatory
504426Mode of action assay-Dose response assay for compounds that inhibit T-type calcium channel subunit Cav3.2 on automated patch clampconfirmatory
504619Inhibitors of T-Type Calcium Channels (Cav3.2 HEK whole cell CRC)confirmatory
504628Inhibitors of T-Type Calcium Channels (Cav3.2 HEK whole cell)other
Description:
Assay Provider: Xinmin Xie
Assay Provider Affiliation: Bioscience Division, SRI International, Menlo Park, CA
Grant Title: HTS Assay for Cav3 T-Type Channels using FLIPR
Grant Number: NS050771-01

T-type Ca2+ channels are also called low voltage-activated channels because they open at voltages near the resting membrane potential of most cells. In many types of neurons, Ca2+ influx through T-type channels triggers low-threshold spikes, which in turn trigger a burst of action potentials mediated by Na+ channels (1). Burst firing is thought to play an important role in the synchronized activity of the thalamus observed in absence epilepsy, and also in a wider range of neurological disorders characterized by thalamocortical dysrhythmia (2). Prominent T-currents are also observed in dorsal root ganglion neurons, with subsets of nociceptors expressing more T-current than high voltage-activated Ca2+ currents (3). Considerable evidence supports the notion that a T-channel antagonist would be a useful drug for the treatment of pain and epilepsy (4).
Protocol
The purpose of this assay was to follow up on the confirmatory and dose-response testing of the validated lead SAR series to characterize the candidate probe compound (ML218) for ancillary pharmacology in counter screens via the commercial Riserca Biosciences, LLC radioligand binding assay panels targeting G-protein coupled receptors, neurotransmitter transporters and ion channels.

Methods employed in this study have been adapted from the scientific literature by Ricerca Biosciences, LLC to maximize reliability and reproducibility. Reference standards were run as an integral part of each assay to ensure the validity of the results obtained. Assays were performed under conditions described in an extensive "Methods" section available from Ricerca Biosciences, LLC using a 10 uM test concentration of ML218 for radioligand and 30uM test concentration for functional assays. Percent inhibition of target-selective radioligand binding or functional response is reported. Under the Ricerca Biosciences, LLC panel assay conditions, responses with greater than 50% inhibition are considered significant.

1.Perez-Reyes, E: Molecular physiology of low-voltage-activated T-type calcium channels. Physiol. Rev. 2003; 83: 117-161.
2.Llinas, R R, Ribary, U, Jeanmonod, D, Kronberg, E, and Mitra, P P: Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc. Natl. Acad. Sci. U.S.A. 1999; 96: 15222-15227.
3.Nelson, M T, Joksovic, P M, Perez-Reyes, E, and Todorovic, S M: The endogenous redox agent L-cysteine induces T-type Ca2+ channel-dependent sensitization of a novel subpopulation of rat peripheral nociceptors. J. Neurosci. 2005; 25: 8766-8775.
4.Nelson, M, Todorovic, S, and Perez-Reyes, E: The role of T-type calcium channels in epilepsy and pain. Curr Pharm Des 2006; 12: 2189-2197.
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Adenosine_A1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
2Adenosine_A2aBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
3Adenosine_A3Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
4Adrenergic_alpha1ABiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
5Adrenergic_alpha1BBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
6Adrenergic_alpha1DBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
7Adrenergic_alpha2ABiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
8Adrenergic_beta1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
9Adrenergic_beta2Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
10Androgen_Testosterone_ARBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
11Bradykinin_B1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
12Bradykinin_B2Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
13Calcium_Channel_Ltype_BenzothiazepineBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
14Calcium_Channel_Ltype_DihydropyridineBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
15Calcium_Channel_NtypeBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
16Cannabinoid_CB1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
17Dopamine_D1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
18Dopamine_D25Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
19Dopamine_D3Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
20Dopamine_D4,2Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
21Endothelin_EtaBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
22Endothelin_EtbBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
23Epidermal_Growth_Factor_EGFBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
24Estrogen_ER_alphaBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
25GABA_A_Flunitrazepam_CentralBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
26GABA_A_Muscimol_CentralBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
27GABA_B_1ABiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
28GlucocorticoidBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
29Glutamate_KainateBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
30Glutamate_NMDA_AgonismBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
31Glutamate_NMDA_GlycineBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
32Glutamate_NMDA_PhencyclidineBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
33Histamine_H1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
34Histamine_H2Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
35Histamine_H3Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
36Imidazoline_I2_CentralBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
37Interleukin_IL1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
38Leukotriene_Cysteinyl_CysLT1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
39Melatonin_MT1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
40Muscarinic_M1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
41Muscarinic_M2Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
42Muscarinic_M3Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
43NeuropeptideY_Y1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
44NeuropeptideY_Y2Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
45Nicotinic_AcetylcholineBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
46Nicotinic_Acetylcholine_alpha1_BungarotoxinBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
47Opiate_delta1_OP1_DOPBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
48Opiate_kappa_OP2_KOPBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
49Opiate_mu_OP3_MOPBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
50Phorbol_EsterBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
51Platelet_Activating_Factor_PAFBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
52Potassium_Channel_K_ATPBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
53Potassium_Channel_hERGBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
54Prostanoid_EP4Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
55Purinergic_P2XYBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
56Purinergic_P2YBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
57RolipramBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
58Serotonin_5HT1ABiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
59Serotonin_5HT2BBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
60Serotonin_5HT3Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
61Sigma_rho1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
62Sodium_Channel_Site2Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
63Tachykinin_NK1Biochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
64Thyroid_HormoneBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
65Transporter_Dopamine_DATBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
66Transporter_GABABiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
67Transporter_Norepinephrine_NETBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
68Transporter_Serotonin_5-Hydroxytryptamine_SERTBiochemical assay results presented as the percent inhibition of specific binding or activity. Primary screening in duplicate with quantitative data (e.g., IC50 +/- SEM, Ki +/- SEM and nH). Significant responses (50% inhibition or stimulation for Biochemical assays).Float%
Additional Information
Grant Number: NS050771-01

Data Table (Concise)
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