lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1(C)OB(c2ccccc2CCSc2ccc(C(=O)Nc3ccc(F)cc3)cn2)OC1(C)C
InChIKey: OLWUHRKWRPFSRU-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
Measurement: IC50 = 611 nM (pChEMBL 6.210000038146973)
Descriptors: MW 478.4
Compound (SMILES): CC1(C)C2CC3OB(c4ccccc4CSc4ccc(C(=O)Nc5ccc(F)cc5)cn4)OC3(C)C1C2
InChIKey: YESROJKMJPAAFH-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 516.45
Compound (SMILES): CC1(C)OB(c2ccc(F)cc2CSc2ccc(C(=O)Nc3ccc(F)cc3)cn2)OC1(C)C
InChIKey: MWQOFNNFABWGQD-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
Measurement: IC50 = 1230 nM (pChEMBL 5.909999847412109)
Descriptors: MW 482.36
Compound (SMILES): CC1(C)OB(c2ccc(OC(F)(F)F)cc2CSc2ccc(C(=O)Nc3ccc(F)cc3)cn2)OC1(C)C
InChIKey: KUUXJYNTDOOIJP-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 548.37
Compound (SMILES): COc1cccc(F)c1CN1C[C@H](NC(=O)c2ccc3[nH]nc(-c4ccnc(C)c4)c3c2)CC[C@H]1C(=O)Nc1ccc(C)nc1
InChIKey: YDIUNBKZEBIPPR-RNAHPLFWSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 607.69, ALogP 5.19, HBA 7, HBD 3, PSA 125.13, QED 0.22
Compound (SMILES): COc1cccc(F)c1CN1C[C@H](NC(=O)c2ccc3[nH]nc(-c4ccnc(C)c4)c3c2)CC[C@H]1C(=O)Nc1cccnc1
InChIKey: VLWYGJMAIORFPU-GIGWZHCTSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 593.66, ALogP 4.88, HBA 7, HBD 3, PSA 125.13, QED 0.23
Compound (SMILES): COc1cccc(F)c1CN1C[C@H](NC(=O)c2ccc3[nH]nc(-c4ccnc(C)c4)c3c2)CC[C@H]1C(=O)Nc1nccs1
InChIKey: JCPLREQISQGSMG-RLWLMLJZSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 599.69, ALogP 4.94, HBA 8, HBD 3, PSA 125.13, QED 0.23
Compound (SMILES): COc1ccc(N(C)C(=O)[C@@H]2CC[C@@H](NC(=O)c3ccc4[nH]nc(-c5ccnc(C)c5)c4c3)CN2Cc2c(F)cccc2OC)cc1
InChIKey: UEMBFPUPXGFQHE-GOXGLGGOSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 636.73, ALogP 5.52, HBA 7, HBD 2, PSA 112.68, QED 0.22
Compound (SMILES): COc1ccc(NC(=O)[C@@H]2CC[C@@H](NC(=O)c3ccc4[nH]nc(-c5ccnc(C)c5)c4c3)CN2Cc2c(F)cccc2OC)cc1
InChIKey: ROBZIPSGEAKWCS-NJHZRGNWSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 622.7, ALogP 5.49, HBA 7, HBD 3, PSA 121.47, QED 0.2
Compound (SMILES): COc1cccc(F)c1CN1C[C@H](NC(=O)c2ccc3[nH]nc(-c4ccnc(C)c4)c3c2)CC[C@H]1C(=O)NCC1(CO)CCCC1
InChIKey: KIVNCONDVPRMRL-RNAHPLFWSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 8.8 nM (pChEMBL 8.0600004196167)
Descriptors: MW 628.75, ALogP 4.51, HBA 7, HBD 4, PSA 132.47, QED 0.2
Compound (SMILES): COc1ccnc(NC(=O)[C@@H]2CC[C@@H](NC(=O)c3ccc4[nH]nc(-c5ccnc(C)c5)c4c3)CN2Cc2c(F)cccc2OC)c1
InChIKey: IPGPAIVNNKYGGU-BTYSJIOQSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 50.2 nM (pChEMBL 7.300000190734863)
Descriptors: MW 623.69, ALogP 4.89, HBA 8, HBD 3, PSA 134.36, QED 0.21
Compound (SMILES): COc1cccc(F)c1CN1C[C@H](NC(=O)c2ccc3[nH]nc(-c4ccnc(C)c4)c3c2)CC[C@H]1C(=O)Nc1cccc(F)c1
InChIKey: GZKNUMYRVBIKSA-RNAHPLFWSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 15.2 nM (pChEMBL 7.820000171661377)
Descriptors: MW 610.66, ALogP 5.62, HBA 6, HBD 3, PSA 112.24, QED 0.21
Compound (SMILES): COc1ccc(NC(=O)[C@@H]2CC[C@@H](NC(=O)c3ccc4[nH]nc(-c5ccnc(C)c5)c4c3)CN2Cc2c(F)cccc2OC)cc1F
InChIKey: YLCYDGQQQDNJAT-HLADLETHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 16.7 nM (pChEMBL 7.78000020980835)
Descriptors: MW 640.69, ALogP 5.63, HBA 7, HBD 3, PSA 121.47, QED 0.19
Compound (SMILES): COc1cccc(F)c1CN1C[C@H](NC(=O)c2ccc3[nH]nc(-c4ccnc(C)c4)c3c2)CC[C@H]1C(=O)Nc1ccc(F)cc1
InChIKey: XNYOTYDLDFLOHM-RNAHPLFWSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 23.4 nM (pChEMBL 7.630000114440918)
Descriptors: MW 610.66, ALogP 5.62, HBA 6, HBD 3, PSA 112.24, QED 0.21
Compound (SMILES): COc1cccc(F)c1CN1C[C@H](NC(=O)c2ccc3[nH]nc(-c4ccnc(C)c4)c3c2)CC[C@H]1C(=O)Nc1ccc(C)cc1C
InChIKey: MEAMTSUTDFNTRZ-DICHSLLOSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 54.8 nM (pChEMBL 7.260000228881836)
Descriptors: MW 620.73, ALogP 6.1, HBA 6, HBD 3, PSA 112.24, QED 0.19
Compound (SMILES): COc1cccc(F)c1CN1C[C@H](NC(=O)c2ccc3[nH]nc(-c4ccnc(C)c4)c3c2)CC[C@H]1C(=O)N1CCC(O)CC1
InChIKey: HKZIVOGNJIQLNX-BTYSJIOQSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 14.6 nM (pChEMBL 7.840000152587891)
Descriptors: MW 600.7, ALogP 3.83, HBA 7, HBD 3, PSA 123.68, QED 0.29
Compound (SMILES): O=C(NC1CCCN(Cc2ccccc2F)C1)c1ccc2[nH]nc(-c3ccncc3)c2c1
InChIKey: NWDKBBCVWYJPGV-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 429.5, ALogP 4.16, HBA 4, HBD 2, PSA 73.91, QED 0.5
Compound (SMILES): O=C(NC1CCCN(Cc2ccccc2)C1)c1ccc2[nH]nc(-c3ccncc3)c2c1
InChIKey: RJCLUDCGUNLXRQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 411.51, ALogP 4.02, HBA 4, HBD 2, PSA 73.91, QED 0.52
Compound (SMILES): CC(C)Oc1ccc(-c2n[nH]c3ccc(C(=O)NC4CCCN(Cc5ccccc5F)C4)cc23)cn1
InChIKey: OERGTYGYDNZDQC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 487.58, ALogP 4.95, HBA 5, HBD 2, PSA 83.14, QED 0.39
Compound (SMILES): O=C(NC1CCCN(Cc2ccccc2)C1)c1ccc2[nH]nc(-c3ccc4c(c3)CCO4)c2c1
InChIKey: LOSHORMGXMXYQC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 452.56, ALogP 4.56, HBA 4, HBD 2, PSA 70.25, QED 0.47
Compound (SMILES): O=C(NC1CCCN(Cc2ccccc2F)C1)c1ccc2[nH]nc(-c3ccc4c(c3)CCO4)c2c1
InChIKey: NGLSLPSSSLAXOR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 470.55, ALogP 4.7, HBA 4, HBD 2, PSA 70.25, QED 0.44
Compound (SMILES): CC(c1ccccc1)N1CCC[C@@H](NC(=O)c2ccc3[nH]nc(-c4ccncc4)c3c2)C1
InChIKey: VHXZZVVEYNDDCT-LMNIDFBRSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 804 nM (pChEMBL 6.090000152587891)
Descriptors: MW 425.54, ALogP 4.58, HBA 4, HBD 2, PSA 73.91, QED 0.49
Compound (SMILES): O=C(N[C@@H]1CNCC[C@H]1c1ccccc1)c1ccc2[nH]nc(-c3ccc4c(c3)CCO4)c2c1
InChIKey: HSMXSFDYKLGHQK-XUZZJYLKSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 438.53, ALogP 4.04, HBA 4, HBD 3, PSA 79.04, QED 0.45
Compound (SMILES): CN1CC[C@@H](c2ccccc2)[C@H](NC(=O)c2ccc3[nH]nc(-c4ccc5c(c4)CCO5)c3c2)C1
InChIKey: VEPXAHSDPICRRR-WIOPSUGQSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 118.5 nM (pChEMBL 6.929999828338623)
Descriptors: MW 452.56, ALogP 4.38, HBA 4, HBD 2, PSA 70.25, QED 0.48
Compound (SMILES): O=C(N[C@@H]1CNCC[C@H]1c1ccccc1)c1ccc2[nH]nc(-c3ccc4c(c3)OCO4)c2c1
InChIKey: RNSZHCYOFXVMOR-SIKLNZKXSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 27.1 nM (pChEMBL 7.570000171661377)
Descriptors: MW 440.5, ALogP 3.83, HBA 5, HBD 3, PSA 88.27, QED 0.45
Compound (SMILES): O=C(N[C@@H]1CNCC[C@H]1c1ccccc1)c1ccc2[nH]nc(-c3ccc4[nH]c(=O)[nH]c4c3)c2c1
InChIKey: MUFZOTICZKQQRW-FDDCHVKYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 50.1 nM (pChEMBL 7.300000190734863)
Descriptors: MW 452.52, ALogP 3.28, HBA 4, HBD 5, PSA 118.46, QED 0.29
Compound (SMILES): CC(C)Oc1ccc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CNCC[C@H]4c4ccccc4)cc23)cc1
InChIKey: PDKVZEVLEOZULX-JYFHCDHNSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 49.9 nM (pChEMBL 7.300000190734863)
Descriptors: MW 454.57, ALogP 4.89, HBA 4, HBD 3, PSA 79.04, QED 0.39
Compound (SMILES): CCN1CC[C@@H](c2ccccc2)[C@H](NC(=O)c2ccc3[nH]nc(-c4ccc(OC(C)C)cc4)c3c2)C1
InChIKey: VWHNCUHKOBNLGO-LBNVMWSVSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 482.63, ALogP 5.62, HBA 4, HBD 2, PSA 70.25, QED 0.36
Compound (SMILES): CC(C)Oc1ccc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CN(C)CC[C@H]4c4ccccc4)cc23)cc1
InChIKey: LSAFPRADYPISTQ-RPLLCQBOSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 468.6, ALogP 5.23, HBA 4, HBD 2, PSA 70.25, QED 0.41
Compound (SMILES): CC(C)Oc1ccc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CNCC[C@H]4c4ccccc4)cc23)cn1
InChIKey: LNADTIOIDHWGGT-XUZZJYLKSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 84.9 nM (pChEMBL 7.070000171661377)
Descriptors: MW 455.56, ALogP 4.29, HBA 5, HBD 3, PSA 91.93, QED 0.4
Compound (SMILES): CC(C)Oc1ccc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CN(C)CC[C@H]4c4ccccc4)cc23)cn1
InChIKey: CKYVDAABVXTGQD-WIOPSUGQSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 469.59, ALogP 4.63, HBA 5, HBD 2, PSA 83.14, QED 0.43
Compound (SMILES): CCN1CC[C@@H](c2ccccc2)[C@H](NC(=O)c2ccc3[nH]nc(-c4ccc(OC(C)C)nc4)c3c2)C1
InChIKey: VIUCOJVTEBFQGR-JYFHCDHNSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 483.62, ALogP 5.02, HBA 5, HBD 2, PSA 83.14, QED 0.39
Compound (SMILES): CC(C)(C)OC(=O)N1CC[C@@H](c2ccccc2)[C@H](NC(=O)c2ccc3[nH]nc(-c4ccc5c(c4)CCO5)c3c2)C1
InChIKey: LPDUIFFMNXGVLY-RPLLCQBOSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 538.65, ALogP 5.69, HBA 5, HBD 2, PSA 96.55, QED 0.35
Compound (SMILES): O=C(N[C@@H]1CNCC[C@H]1c1ccccc1)c1ccc2[nH]nc(-c3ccc4[nH]ncc4c3)c2c1
InChIKey: JLWDWMQHZAPGDG-GBXCKJPGSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 13.7 nM (pChEMBL 7.860000133514404)
Descriptors: MW 436.52, ALogP 3.98, HBA 4, HBD 4, PSA 98.49, QED 0.34
Compound (SMILES): CC(C)Oc1cc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CNCC[C@H]4c4ccccc4)cc23)ccn1
InChIKey: WKRDROMNWAJXCR-XUZZJYLKSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 141.3 nM (pChEMBL 6.849999904632568)
Descriptors: MW 455.56, ALogP 4.29, HBA 5, HBD 3, PSA 91.93, QED 0.4
Compound (SMILES): COc1cc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CCCN(Cc5ccccc5F)C4)cc23)ccn1
InChIKey: NCESPKIIXIBQOV-HXUWFJFHSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 0.81 nM (pChEMBL 9.09000015258789)
Descriptors: MW 459.53, ALogP 4.17, HBA 5, HBD 2, PSA 83.14, QED 0.45
Compound (SMILES): O=C(N[C@@H]1CCCN(Cc2ccccc2F)C1)c1ccc2[nH]nc(-c3ccnc(C4CC4)c3)c2c1
InChIKey: CDEHDHKGIDYYRX-JOCHJYFZSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 469.56, ALogP 5.04, HBA 4, HBD 2, PSA 73.91, QED 0.42
Compound (SMILES): CCc1cc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CCCN(Cc5ccccc5F)C4)cc23)ccn1
InChIKey: KNTCUAGFDQLPNM-JOCHJYFZSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 457.55, ALogP 4.72, HBA 4, HBD 2, PSA 73.91, QED 0.44
Compound (SMILES): Cc1cc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CCCN(Cc5ccccc5F)C4)cc23)ccn1
InChIKey: IENYRPIWYCLETB-OAQYLSRUSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 443.53, ALogP 4.47, HBA 4, HBD 2, PSA 73.91, QED 0.48