lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(F)ccc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: JZEGKROGVZUIKH-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 450.34, ALogP 4.99, HBA 5, HBD 2, PSA 97.75, QED 0.51
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(C(F)(F)F)ccc2Oc2ccc(F)cc2Cl)cn1
InChIKey: ZJDFLPLEPVWDIP-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 454.76, ALogP 5.64, HBA 4, HBD 2, PSA 88.52, QED 0.49
Compound (SMILES): COc1ccc(F)cc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: SDECKQPUJVAGMH-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 450.34, ALogP 4.99, HBA 5, HBD 2, PSA 97.75, QED 0.51
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(C(F)(F)F)ccc2Oc2ccccc2OC(F)F)cn1
InChIKey: IBWZICSHYIJAQF-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 468.33, ALogP 5.44, HBA 5, HBD 2, PSA 97.75, QED 0.45
Compound (SMILES): Cc1cc(Cl)ccc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: RRSGOCVSLFHGAX-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 450.8, ALogP 5.81, HBA 4, HBD 2, PSA 88.52, QED 0.51
Compound (SMILES): COc1ccccc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: BQNMADFVJFWVJU-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 432.35, ALogP 4.85, HBA 5, HBD 2, PSA 97.75, QED 0.58
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(C(F)(F)F)ccc2Oc2ccccc2Cl)cn1
InChIKey: QPVZBOZWYRYQOY-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 436.77, ALogP 5.5, HBA 4, HBD 2, PSA 88.52, QED 0.55
Compound (SMILES): CC(C)Oc1ccccc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: SCVAJTQTAYTWBF-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 755 nM (pChEMBL 6.119999885559082)
Descriptors: MW 460.41, ALogP 5.63, HBA 5, HBD 2, PSA 97.75, QED 0.47
Compound (SMILES): COc1cc(CO)ccc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: NBJYWYJDLWFCJP-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 462.38, ALogP 4.34, HBA 6, HBD 3, PSA 117.98, QED 0.48
Compound (SMILES): COc1cc(Cl)ccc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: IPADATBHURPXJO-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 466.8, ALogP 5.51, HBA 5, HBD 2, PSA 97.75, QED 0.5
Compound (SMILES): Cc1cc(CO)ccc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: GRNVPYIZGJJMAT-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 446.38, ALogP 4.64, HBA 5, HBD 3, PSA 108.75, QED 0.51
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(C(F)(F)F)ccc2Oc2ccc(CO)cc2Cl)cn1
InChIKey: DTYUHFLYQVMLFJ-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 135 nM (pChEMBL 6.869999885559082)
Descriptors: MW 466.8, ALogP 4.99, HBA 5, HBD 3, PSA 108.75, QED 0.47
Compound (SMILES): COc1c(F)cccc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: BIRRZQIINJYINB-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 135 nM (pChEMBL 6.869999885559082)
Descriptors: MW 450.34, ALogP 4.99, HBA 5, HBD 2, PSA 97.75, QED 0.51
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(C(F)(F)F)ccc2Oc2ccccc2)cn1
InChIKey: QAJFPIFCJNLXPC-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 985 nM (pChEMBL 6.010000228881836)
Descriptors: MW 402.33, ALogP 4.84, HBA 4, HBD 2, PSA 88.52, QED 0.64
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(C(F)(F)F)ccc2Oc2ccc(F)cc2)cn1
InChIKey: RJLRXYFRSLFOCO-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 285 nM (pChEMBL 6.539999961853027)
Descriptors: MW 420.32, ALogP 4.98, HBA 4, HBD 2, PSA 88.52, QED 0.57
Compound (SMILES): COc1cc(F)ccc1Oc1cc(C(F)(F)C(F)(F)F)ccc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: VCYKKUVBCWYYMM-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 500.35, ALogP 5.63, HBA 5, HBD 2, PSA 97.75, QED 0.41
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2ccc(C(F)(F)C(F)(F)F)cc2Oc2ccc(F)cc2)cn1
InChIKey: YVIUQKQGEHIQQT-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 470.32, ALogP 5.62, HBA 4, HBD 2, PSA 88.52, QED 0.46
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2c(Oc3ccc(F)cc3Cl)cccc2C(F)(F)F)cn1
InChIKey: KTHRLYGNINDXBX-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 405 nM (pChEMBL 6.389999866485596)
Descriptors: MW 454.76, ALogP 5.64, HBA 4, HBD 2, PSA 88.52, QED 0.49
Compound (SMILES): Cc1cc(F)ccc1Oc1ccc(C(F)(F)F)cc1C(=O)Nc1ccc(C(=O)O)nc1
InChIKey: AKOGFIZZLZJNQH-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 434.35, ALogP 5.29, HBA 4, HBD 2, PSA 88.52, QED 0.53
Compound (SMILES): CCC(=N\O)/C(C)=C/c1ccc(F)cc1
InChIKey: HKROEBDHHKMNBZ-CHBKHGQFSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: GPCRScan assay: inhibition of Sigma 1
Measurement: Ki = 505.48 nM (pChEMBL 6.300000190734863)
Descriptors: MW 207.25, ALogP 3.47, HBA 2, HBD 1, PSA 32.59, QED 0.46
Compound (SMILES): CCC(=N\OC)/C(C)=C/c1ccc(F)cc1
InChIKey: LWLNRICWXNERKX-PANOFWHVSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 221.28, ALogP 3.64, HBA 2, HBD 0, PSA 21.59, QED 0.56
Compound (SMILES): CCC(=N\O)/C(C)=C/c1ccccc1F
InChIKey: WBVIPJUKXQYVQJ-CHBKHGQFSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 207.25, ALogP 3.47, HBA 2, HBD 1, PSA 32.59, QED 0.46
Compound (SMILES): CCCC(=N\O)/C(C)=C/c1ccc(F)cc1
InChIKey: SSRZLDGEGHSZEF-PANOFWHVSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 221.28, ALogP 3.86, HBA 2, HBD 1, PSA 32.59, QED 0.47
Compound (SMILES): CC(=C\c1ccc(F)cc1)/C(=N/O)C(C)(C)C
InChIKey: ALDVAWDTIJSMNO-ZDHWLGKOSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 235.3, ALogP 4.11, HBA 2, HBD 1, PSA 32.59, QED 0.47
Compound (SMILES): CCCCC(=N\O)/C(C)=C/c1ccc(F)cc1
InChIKey: ALEGZXFLOSZQFJ-OIPGSKEASA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 235.3, ALogP 4.25, HBA 2, HBD 1, PSA 32.59, QED 0.46
Compound (SMILES): CC(=C\c1ccc(F)cc1)/C(=N\O)C(C)C
InChIKey: KHBHURZBJBAUPN-MBBMFPOLSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 221.28, ALogP 3.72, HBA 2, HBD 1, PSA 32.59, QED 0.47
Compound (SMILES): CC(=C\c1ccc(F)cc1)/C(=N/O)C(C)C
InChIKey: KHBHURZBJBAUPN-MZRBSKCNSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 221.28, ALogP 3.72, HBA 2, HBD 1, PSA 32.59, QED 0.47
Compound (SMILES): CCC(=N\O)/C(C)=C/c1ccc(F)c(Cl)c1
InChIKey: REQRXYTVHDTROQ-QWPOMPHKSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 241.69, ALogP 4.12, HBA 2, HBD 1, PSA 32.59, QED 0.48
Compound (SMILES): CCC(=N/O)/C(C)=C/c1ccc(F)cc1
InChIKey: HKROEBDHHKMNBZ-BYKJOZEVSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 701 nM (pChEMBL 6.150000095367432)
Descriptors: MW 207.25, ALogP 3.47, HBA 2, HBD 1, PSA 32.59, QED 0.46
Compound (SMILES): CC(/C=C/c1ccc(F)cc1)=N\O
InChIKey: APCBJCFILSRMRW-NQPRBDNZSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 20600 nM (pChEMBL 4.690000057220459)
Descriptors: MW 179.19, ALogP 2.69, HBA 2, HBD 1, PSA 32.59, QED 0.42
Compound (SMILES): CCCC(/C=C/c1ccc(F)cc1)=N\O
InChIKey: GVMNKKDSUMTDFH-TZOAMJEDSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 5910 nM (pChEMBL 5.230000019073486)
Descriptors: MW 207.25, ALogP 3.47, HBA 2, HBD 1, PSA 32.59, QED 0.46
Compound (SMILES): CCC(/C=C/c1ccc(F)cc1)=N\O
InChIKey: GLYGZIVKLCTOTJ-PGMBSLALSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 9460 nM (pChEMBL 5.019999980926514)
Descriptors: MW 193.22, ALogP 3.08, HBA 2, HBD 1, PSA 32.59, QED 0.45
Compound (SMILES): CCC(=N\O)/C(C)=C/c1ccc(F)c(F)c1
InChIKey: WRDLKTQRPOZITC-QWPOMPHKSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 574 nM (pChEMBL 6.239999771118164)
Descriptors: MW 225.24, ALogP 3.61, HBA 2, HBD 1, PSA 32.59, QED 0.48
Compound (SMILES): CCC(=N\O)/C(C)=C/c1cc(F)c(F)c(F)c1
InChIKey: FPMULNOOMRYVLW-UYHGDYIZSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 = 4670 nM (pChEMBL 5.329999923706055)
Descriptors: MW 243.23, ALogP 3.75, HBA 2, HBD 1, PSA 32.59, QED 0.37
Compound (SMILES): CCCCC(/C=C/c1ccc(F)cc1)=N\O
InChIKey: AOMKWGBGGCJRQG-GRVINKSSSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Calcium Assay: Ca2+ influx was measured using a FLIPR calcium assay kit (R8033; Molecular Devices, Sunnyvale, Calif.). The Ca2+ indicator dye was dissolved in Hanks' balanced salt solution supplemented with 20 mM HEPES buffer (HBSS/HEPES) according to the manufacturer instructions. Prior to start of the assay, the medium was removed by aspiration, and cells were loaded with 100 μL Ca2+ dye for 2 to 3 hours at room temperature. AITC (allyl isothiocyanate) was used to activate and open the channels. (4×) solutions of the test compounds were prepared in HBSS/HEPES, and 50 μL were added to the cells at a delivery rate of 10 μL/sec. Changes in fluorescence were measured over time in a fluorometric imaging plate reader (FLIPR, Molecular Devices). Two additions were made over the course of an experimental run. For agonist experiments, assay buffer was added at the 10 s time point, followed by addition of agonist at the 3 minute 10 sec time point.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 221.28, ALogP 3.86, HBA 2, HBD 1, PSA 32.59, QED 0.46
Compound (SMILES): Cc1ccc(C(=O)Nc2cc(N(C)CCN(C)C)cc(C(F)(F)F)c2)cc1Nc1ncnc2cnc(NC3CC3)nc12
InChIKey: VKPLTNDXXKBIJZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: kinase Assay: The final concentration of DMSO is 5%. 10 μL of the B-Raf (V600E)-kinase solution are pipetted in (containing 0.5 ng B-Raf (V600E)-kinase in 20 mM Tris-HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol, 1 mg/mL bovine serum albumin, 1 mM dithiothreitol) and the mixture is incubated for 24 h at RT under with shaking. The kinase reaction is started by the addition of 20 μL ATP solution [final concentration: 250 μM ATP, 30 mM Tris-HCl pH 7.5, 0.02% Brij, 0.2 mM sodium orthovanadate, 10 mM magnesium acetate, 0.1 mM EGTA, phosphatase cocktail (Sigma, # P2850, dilution recommended by the manufacturer), 0.1 mM EGTA] and 10 μL MEK1 solution [containing 50 ng biotinylated MEK1 (prepared from purified MEK1 according to standard procedure, e.g. with EZ-Link Sulpho-NHS-LC-Biotin reagent, Pierce, #21335) and carried out for 60 min at RT with constant shaking.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 579.63, ALogP 5.32, HBA 9, HBD 3, PSA 111.2, QED 0.23
Compound (SMILES): Cc1ccc(C(=O)Nc2cc(N(C)CCN(C)C)cc(C(F)(F)F)c2)cc1Nc1ncnc2cnc(NCC(C)C)nc12
InChIKey: QPFFJQYDLOSUHI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: kinase Assay: The final concentration of DMSO is 5%. 10 μL of the B-Raf (V600E)-kinase solution are pipetted in (containing 0.5 ng B-Raf (V600E)-kinase in 20 mM Tris-HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol, 1 mg/mL bovine serum albumin, 1 mM dithiothreitol) and the mixture is incubated for 24 h at RT under with shaking. The kinase reaction is started by the addition of 20 μL ATP solution [final concentration: 250 μM ATP, 30 mM Tris-HCl pH 7.5, 0.02% Brij, 0.2 mM sodium orthovanadate, 10 mM magnesium acetate, 0.1 mM EGTA, phosphatase cocktail (Sigma, # P2850, dilution recommended by the manufacturer), 0.1 mM EGTA] and 10 μL MEK1 solution [containing 50 ng biotinylated MEK1 (prepared from purified MEK1 according to standard procedure, e.g. with EZ-Link Sulpho-NHS-LC-Biotin reagent, Pierce, #21335) and carried out for 60 min at RT with constant shaking.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 595.67, ALogP 5.81, HBA 9, HBD 3, PSA 111.2, QED 0.2
Compound (SMILES): Cc1ccc(C(=O)Nc2cc(N(C)CCN(C)C)cc(C(F)(F)F)c2)cc1Nc1ncnc2cnc(NCc3ccccn3)nc12
InChIKey: LFUHZURAYFMLOU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: kinase Assay: The final concentration of DMSO is 5%. 10 μL of the B-Raf (V600E)-kinase solution are pipetted in (containing 0.5 ng B-Raf (V600E)-kinase in 20 mM Tris-HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol, 1 mg/mL bovine serum albumin, 1 mM dithiothreitol) and the mixture is incubated for 24 h at RT under with shaking. The kinase reaction is started by the addition of 20 μL ATP solution [final concentration: 250 μM ATP, 30 mM Tris-HCl pH 7.5, 0.02% Brij, 0.2 mM sodium orthovanadate, 10 mM magnesium acetate, 0.1 mM EGTA, phosphatase cocktail (Sigma, # P2850, dilution recommended by the manufacturer), 0.1 mM EGTA] and 10 μL MEK1 solution [containing 50 ng biotinylated MEK1 (prepared from purified MEK1 according to standard procedure, e.g. with EZ-Link Sulpho-NHS-LC-Biotin reagent, Pierce, #21335) and carried out for 60 min at RT with constant shaking.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 630.68, ALogP 5.75, HBA 10, HBD 3, PSA 124.09, QED 0.17
Compound (SMILES): Cc1ccc(C(=O)Nc2cc(N(C)CCN(C)C)cc(C(F)(F)F)c2)cc1Nc1ncnc2cnc(NCc3ccncc3)nc12
InChIKey: JKNYELDCOXITQY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: kinase Assay: The final concentration of DMSO is 5%. 10 μL of the B-Raf (V600E)-kinase solution are pipetted in (containing 0.5 ng B-Raf (V600E)-kinase in 20 mM Tris-HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol, 1 mg/mL bovine serum albumin, 1 mM dithiothreitol) and the mixture is incubated for 24 h at RT under with shaking. The kinase reaction is started by the addition of 20 μL ATP solution [final concentration: 250 μM ATP, 30 mM Tris-HCl pH 7.5, 0.02% Brij, 0.2 mM sodium orthovanadate, 10 mM magnesium acetate, 0.1 mM EGTA, phosphatase cocktail (Sigma, # P2850, dilution recommended by the manufacturer), 0.1 mM EGTA] and 10 μL MEK1 solution [containing 50 ng biotinylated MEK1 (prepared from purified MEK1 according to standard procedure, e.g. with EZ-Link Sulpho-NHS-LC-Biotin reagent, Pierce, #21335) and carried out for 60 min at RT with constant shaking.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 630.68, ALogP 5.75, HBA 10, HBD 3, PSA 124.09, QED 0.17