GDC-0276 [Ligand Id: 12779] activity data from GtoPdb and ChEMBL
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| ChEMBL ligand: CHEMBL3657855 |
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| DB | Assay description | Assay Type | Standard value | Standard parameter | Original value | Original units | Original parameter | Reference |
|---|---|---|---|---|---|---|---|---|
| Nav1.1/Sodium channel protein type 1 subunit alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1845] [GtoPdb: 578] [UniProtKB: P35498] | ||||||||
| ChEMBL | Inhibition of human Nav1.1 expressed in HEK293 cells by electrophysiology assay | B | 7.96 | pIC50 | 11 | nM | IC50 | J Med Chem (2019) 62: 8695-8710 [PMID:31012583] |
| ChEMBL | Inhibition of full length human Nav1.1 expressed in HEK cells by whole cell voltage clamp analysis | B | 7.97 | pIC50 | 10.6 | nM | IC50 | J Med Chem (2021) 64: 2953-2966 [PMID:33682420] |
| Nav1.2/Sodium channel protein type 2 subunit alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4187] [GtoPdb: 579] [UniProtKB: Q99250] | ||||||||
| ChEMBL | Inhibition of human Nav1.2 expressed in HEK293 cells by electrophysiology assay | B | 7.7 | pIC50 | 20 | nM | IC50 | J Med Chem (2019) 62: 8695-8710 [PMID:31012583] |
| ChEMBL | Inhibition of full length human Nav1.2 expressed in HEK cells by whole cell voltage clamp analysis | B | 7.72 | pIC50 | 18.9 | nM | IC50 | J Med Chem (2021) 64: 2953-2966 [PMID:33682420] |
| Nav1.4/Sodium channel protein type 4 subunit alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2072] [GtoPdb: 581] [UniProtKB: P35499] | ||||||||
| ChEMBL | Inhibition of full length human Nav1.4 expressed in HEK cells by whole cell voltage clamp analysis | B | 8.07 | pIC50 | 8.5 | nM | IC50 | J Med Chem (2021) 64: 2953-2966 [PMID:33682420] |
| Nav1.5/Sodium channel protein type 5 subunit alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1980] [GtoPdb: 582] [UniProtKB: Q14524] | ||||||||
| ChEMBL | Inhibition of human Nav1.5 expressed in HEK293 cells incubated for 1 hr in presence of veratridine and anthropleurin-C by sodium influx assay | B | 6.06 | pIC50 | 870 | nM | IC50 | J Med Chem (2021) 64: 2953-2966 [PMID:33682420] |
| ChEMBL | Electrophysiological Assay: Patch voltage clamp electrophysiology allows for the direct measurement and quantification of block of voltage-gated sodium channels (NaV's), and allows the determination of the time- and voltage-dependence of block which has been interpreted as differential binding to the resting, open, and inactivated states of the sodium channel (Hille, B., Journal of General Physiology (1977), 69: 497-515).The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel alpha -subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37 C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating. | B | 7.29 | pIC50 | 51.5 | nM | IC50 | US-8952169-B2. N-substituted benzamides and methods of use thereof (2015) |
| ChEMBL | Inhibition of full length human Nav1.5 expressed in HEK cells by whole cell voltage clamp analysis | B | 7.29 | pIC50 | 51 | nM | IC50 | J Med Chem (2021) 64: 2953-2966 [PMID:33682420] |
| ChEMBL | Inhibition of human Nav1.5 expressed in HEK293 cells by electrophysiology assay | B | 7.31 | pIC50 | 49 | nM | IC50 | J Med Chem (2019) 62: 8695-8710 [PMID:31012583] |
| Sodium channel protein type 7 subunit alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3585] [UniProtKB: Q01118] | ||||||||
| ChEMBL | Inhibition of human Nav1.7 expressed in HEK293 cells incubated for 1 hr in presence of veratridine by sodium influx assay | B | 7.31 | pIC50 | 49 | nM | IC50 | J Med Chem (2021) 64: 2953-2966 [PMID:33682420] |
| ChEMBL | Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay | B | 8.96 | pIC50 | 1.1 | nM | IC50 | J Med Chem (2021) 64: 2953-2966 [PMID:33682420] |
| ChEMBL | Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay | B | 9.4 | pIC50 | 0.4 | nM | IC50 | J Med Chem (2019) 62: 8695-8710 [PMID:31012583] |
| ChEMBL | Inhibition of full length human Nav1.7 expressed in HEK cells by whole cell voltage clamp analysis | B | 9.4 | pIC50 | 0.4 | nM | IC50 | J Med Chem (2021) 64: 2953-2966 [PMID:33682420] |
| Nav1.6/Sodium channel protein type 8 subunit alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5202] [GtoPdb: 583] [UniProtKB: Q9UQD0] | ||||||||
| ChEMBL | Inhibition of human Nav1.6 expressed in HEK293 cells by electrophysiology assay | B | 6.32 | pIC50 | 480 | nM | IC50 | J Med Chem (2019) 62: 8695-8710 [PMID:31012583] |
| ChEMBL | Inhibition of human Nav1.6 expressed in CHO cells by whole cell voltage clamp analysis | B | 6.32 | pIC50 | 480 | nM | IC50 | J Med Chem (2021) 64: 2953-2966 [PMID:33682420] |
| Nav1.7/Sodium channel protein type 9 subunit alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4296] [GtoPdb: 584] [UniProtKB: Q15858] | ||||||||
| ChEMBL | Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments. | B | 8.7 | pIC50 | 2 | nM | IC50 | US-8952169-B2. N-substituted benzamides and methods of use thereof (2015) |
| ChEMBL | Electrophysiological Assay: Patch voltage clamp electrophysiology allows for the direct measurement and quantification of block of voltage-gated sodium channels (NaV's), and allows the determination of the time- and voltage-dependence of block which has been interpreted as differential binding to the resting, open, and inactivated states of the sodium channel (Hille, B., Journal of General Physiology (1977), 69: 497-515).The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel alpha -subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37 C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating. | B | 9.4 | pIC50 | 0.4 | nM | IC50 | US-8952169-B2. N-substituted benzamides and methods of use thereof (2015) |
| ChEMBL | Inhibition of Nav1.7 (unknown origin) by electrophysiology assay | B | 9.4 | pIC50 | 0.4 | nM | IC50 | Bioorg Med Chem Lett (2018) 28: 3141-3149 [PMID:30139550] |
| ChEMBL | Electrophysiological Assay (In Vitro Assay): The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37° C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating. NaV1.7 and NaV1.5 cDNAs (NM_002977 and AC137587; SCN5A, respectively) were stably expressed in HEK-293 cells. The β1 subunit was coexpressed in both the NaV1.7 and NaV1.5 cell lines.Sodium currents were measured using the patch clamp technique in the whole-cell configuration using either a PatchXpress automated voltage clamp or manually using an Axopatch 200B (Axon Instruments) or Model 2400 (A-M systems) amplifier. The manual voltage clamp protocol was as follows: Borosilicate glass micropipettes were fire-polished to a tip diameter yielding a resistance of 2-4 Mohms in the working solutions. The pipette was filled with a solution comprised of: 5 mM NaCl, 10 mM CsCl, 120 mM CsF, 0.1 mM CaCl2, 2 mM MgCl2, 10 mM HEPES, 10 mM EGTA; and adjusted to pH 7.2 with CsOH. The external solution had the following composition: 140 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES; and adjusted to pH 7.4 with NaOH. | B | 9.4 | pIC50 | 0.4 | nM | IC50 | US-9771376-B2. N-substituted benzamides and methods of use thereof (2017) |
| Nav1.7/Sodium channel protein type 9 subunit alpha/beta-1/beta-2 in Human (target type: PROTEIN COMPLEX) [ChEMBL: CHEMBL4630765] [GtoPdb: 584] [UniProtKB: O60939, Q07699, Q15858] | ||||||||
| ChEMBL | Inhibition of human Nav1.7/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis | B | 9.4 | pIC50 | 0.4 | nM | IC50 | ACS Med Chem Lett (2023) 14: 788-793 [PMID:37312847] |
ChEMBL data shown on this page come from version 36:
Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]
