lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COCCOCCN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(N)cc13
InChIKey: VMIWHFQJHHSOSR-TYPHKJRUSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 344.5, ALogP 2.99, HBA 4, HBD 1, PSA 47.72, QED 0.64
Compound (SMILES): COCCOCCN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1cc2sc(N)nc2cc13
InChIKey: MSKNNQUPDKTVGU-NBCNXNJRSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 401.58, ALogP 3.6, HBA 6, HBD 1, PSA 60.61, QED 0.75
Compound (SMILES): COCCOCCN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(Nc2ccncc2)cc13
InChIKey: IVUYTIOTZPFQNJ-DMDYGQEQSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 421.58, ALogP 4.55, HBA 5, HBD 1, PSA 46.62, QED 0.63
Compound (SMILES): COCCOCCN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(Nc2ccnnc2)cc13
InChIKey: HJWUNVQEAYMLGM-CAOCKLPOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 422.57, ALogP 3.94, HBA 6, HBD 1, PSA 59.51, QED 0.65
Compound (SMILES): COCCOCCN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(-c2cn[nH]c2)cc13
InChIKey: YZRJRCHRPHUSRD-QTJGBDASSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 395.55, ALogP 3.8, HBA 4, HBD 1, PSA 50.38, QED 0.72
Compound (SMILES): CN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1cc2ccc(N)nc2cc13
InChIKey: BCQNZUSAYWXZOS-CVAIRZPRSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 307.44, ALogP 3.51, HBA 3, HBD 1, PSA 42.15, QED 0.81
Compound (SMILES): CN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1cc2ccc(=O)[nH]c2cc13
InChIKey: WQXGTBRXNGNOKL-CVAIRZPRSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 308.43, ALogP 3.22, HBA 2, HBD 1, PSA 36.1, QED 0.81
Compound (SMILES): COCCOCCN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(Nc2cncc(F)c2)cc13
InChIKey: CCFHDVWKLJXWCM-DMDYGQEQSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 439.58, ALogP 4.69, HBA 5, HBD 1, PSA 46.62, QED 0.61
Compound (SMILES): COCCOCCN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(Nc2nccs2)cc13
InChIKey: QLECEANEMQBWRJ-FJIJXJHWSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 427.61, ALogP 4.61, HBA 6, HBD 1, PSA 46.62, QED 0.62
Compound (SMILES): COCCOCCN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(-c2ccoc2)cc13
InChIKey: SILMVTUHMWZGJA-CAOCKLPOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 395.54, ALogP 4.67, HBA 4, HBD 0, PSA 34.84, QED 0.64
Compound (SMILES): COCCN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(O)cc13
InChIKey: BRIKJIUSSPUTGA-UHOSZYNNSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 301.43, ALogP 3.1, HBA 3, HBD 1, PSA 32.7, QED 0.93
Compound (SMILES): CN1CC[C@@]23CCCC[C@H]2[C@H]1Cc1ccc(N)cc13
InChIKey: CYPHSPITDGFDMD-UAGQMJEPSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 256.39, ALogP 2.96, HBA 2, HBD 1, PSA 29.26, QED 0.72
Compound (SMILES): CN1CC[C@@]23CCCC[C@@H]2[C@H]1Cc1cc2sc(N)nc2cc13
InChIKey: MFCKRIRSBAZCHR-DWQUBVKVSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Receptor Binding Assay: Affinities of various compounds were measured in vitro using competitive radioligand binding assays. Serial dilutions of test compounds were incubated with membranes prepared from CHO-K1 cells expressing the mu opioid receptor (MOR; for opioid receptor binding) or rat forebrain membranes (for NMDA receptor binding). 2 nM [3H] Naloxone (MOR) or 0.2 nM [3H] MK801 (NMDA) were used as the specific, competitive radioligands. 10 uM Naloxone (MOR), or 10 uM MK801 (NMDA) was used to determine non-specific binding. Bound radioactivity was measured using a scintillation counter & IC50 values for test compounds were determined by non-linear regression analysis using a one-site competition model (Graph Pad Prizm). Due to each test compound being solubilized in a buffered system for the assay, the results presented herein reflect the free base activity.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 313.47, ALogP 3.57, HBA 4, HBD 1, PSA 42.15, QED 0.81
Compound (SMILES): CCOc1cc(-c2ccc(N3CC4C[C@@H](C3)[C@@H]4Oc3ccccn3)nc2)c2c(C#N)cnn2c1
InChIKey: GIWIHPXOSJUIRW-RXBAOPJQSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Enzyme Assay: Wildtype and V804M mutant: Compounds of Formula I were screened for their ability to inhibit wildtype and V804M mutant RET kinase using CisBio's HTRF® KinEASE-TK assay technology. Briefly, N-terminal GST tagged recombinant human RET cytoplasmic domain (aa 658-end) from Eurofins (0.25 nM RET; Catalog No. 14-570M) or N-terminal GST tagged recombinant human V804M mutant RET cytoplasmic domain (aa 658-end) from Millipore (0.25 nM enzyme; Catalog No. 14-760) was incubated with 250 nM TK-substrate biotin (CisBio, part of Catalog No. 62TK0PEC) and 1 mM ATP along with test compound in a buffer consisting of 25 mM HEPES pH 7.4, 10 mM MgCl2, 0.01% Triton X-100, and 2% DMSO in a volume of 8 μL. Compounds were typically prepared in a threefold serial dilution in DMSO and added to the assay to give the appropriate final concentration. After a 30-minute incubation at 22° C., the reaction was quenched by adding 8 μL of quench solution containing 31.25 nM Sa-XL665 and 1×TK-ab-Cryptate in HTRF detection buffer (all from CisBio, part of Cat. No. 62TK0PEC). After a 1 hour incubation at 22° C., the extent of reaction was determined using a PerkinElmer EnVision multimode plate reader via HTRF dual wavelength detection, and the percent of control (POC) was calculated using a ratiometric emission factor. 100 POC was determined using no test compounds and 0 POC was determined using pre-quenched control reactions. The POC values were fit to a 4 parameter logistic curve, and the IC50 is defined as the concentration of inhibitor at which the POC equals 50 for the fitted curve.
Measurement: IC50 = 199 nM (pChEMBL 6.699999809265137)
Descriptors: MW 452.52, ALogP 3.97, HBA 8, HBD 0, PSA 88.57, QED 0.44
Compound (SMILES): CC(=O)c1nn(CC(=O)N2C3CCC(CC3)[C@H]2C(=O)Nc2nc(Br)ccc2C)c2ccc(-c3cnc(C)nc3)cc12
InChIKey: JJHWHEJTQMJEMU-CWYPTGNGSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Factor D Assay: Human Factor D (purified from human serum, Complement Technology, Inc.) at 80 nM final concentration is incubated with test compound at various concentrations for 5 min at room temperature in 50 mM Tris, 1M NaCl, pH 7.5. A synthetic substrate Z-L-Lys-SBz and DTNB (Ellman's reagent) are added to final concentrations of 100 μM each. Absorbance at 405 nm (A405) is recorded at 30 second intervals for 30 min using a microplate spectrophotometer. IC50 values are calculated by nonlinear regression of complement Factor D reaction rates as a function of test compound concentration.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 616.52, ALogP 4.88, HBA 8, HBD 1, PSA 122.97, QED 0.24
Compound (SMILES): COc1cc(C(=O)O)cc2sc(N3[C@@H]4CC[C@@]3(C)C[C@H](OC(=O)c3c(C56CCC(CC5)CC6)noc3C3CC3)C4)nc12.O
InChIKey: SDICVDPCRIORDL-HCZGFJFQSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Ligand Binding Assay: The affinity of FXR ligands for the ligand binding domain of FXR was determined using a commercially available human FXR ligand binding assay (LanthaScreen, Thermofisher Cat #PV4833). The purified ligand binding domain of human FXR tagged with GST (glutathiones-S-transferase) is incubated with a terbium labelled anti-GLT antibody and a fluorescein-labelled SRC2-2 peptide (LKEKHKILHRLLQDSSSPV (SEQ ID No.: 1)). Binding of FXR ligands to the FXR ligand binding domain promotes binding of the fluorescein-labelled SRC2-2 peptide. This causes a FRET signal between the terbium-labelled anti-GST antibody and the fluorescein-labelled SRC peptide which are both bound to the FXR ligand binding domain.Test compounds are dissolved in DMSO and a 3-fold serial dilution series is generated, then further diluted into assay buffer. The compounds are mixed with 5 nM GST-tagged FXR ligand binding domain, 5 nM Tb-labelled anti-GST antibody and 500 nM fluorcscein-labelled SRC2-2 peptide in a pH 7.4 buffer. The reaction is incubated at room temperature for 1 hour, then the FRET signal is measured as the ratio of the 520 nm/495 nm emission following excitation at 340 nm.
Measurement: EC50 < 31623 nM (pChEMBL 4.5)
Descriptors: MW 591.73, ALogP 6.84, HBA 9, HBD 1, PSA 114.99, QED 0.29
Compound (SMILES): CC(=O)NS(=O)(=O)c1ccc(N2[C@@H]3CC[C@H]2C[C@@H](OC(=O)c2c(-c4c(Cl)cccc4Cl)noc2C2CC2)C3)cc1
InChIKey: AEPMWSVQQSWTMF-PMOLBWCYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Ligand Binding Assay: The affinity of FXR ligands for the ligand binding domain of FXR was determined using a commercially available human FXR ligand binding assay (LanthaScreen, Thermofisher Cat #PV4833). The purified ligand binding domain of human FXR tagged with GST (glutathiones-S-transferase) is incubated with a terbium labelled anti-GLT antibody and a fluorescein-labelled SRC2-2 peptide (LKEKHKILHRLLQDSSSPV (SEQ ID No.: 1)). Binding of FXR ligands to the FXR ligand binding domain promotes binding of the fluorescein-labelled SRC2-2 peptide. This causes a FRET signal between the terbium-labelled anti-GST antibody and the fluorescein-labelled SRC peptide which are both bound to the FXR ligand binding domain.Test compounds are dissolved in DMSO and a 3-fold serial dilution series is generated, then further diluted into assay buffer. The compounds are mixed with 5 nM GST-tagged FXR ligand binding domain, 5 nM Tb-labelled anti-GST antibody and 500 nM fluorcscein-labelled SRC2-2 peptide in a pH 7.4 buffer. The reaction is incubated at room temperature for 1 hour, then the FRET signal is measured as the ratio of the 520 nm/495 nm emission following excitation at 340 nm.
Measurement: EC50 = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 604.51, ALogP 5.71, HBA 8, HBD 1, PSA 118.81, QED 0.34
Compound (SMILES): CC(=O)NS(=O)(=O)CCCCc1ccc(N2[C@@H]3CC[C@H]2C[C@@H](OC(=O)c2c(-c4c(Cl)cccc4Cl)noc2C2CC2)C3)cc1
InChIKey: YJVPOKXHKSOUOF-LNWKWYTESA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Ligand Binding Assay: The affinity of FXR ligands for the ligand binding domain of FXR was determined using a commercially available human FXR ligand binding assay (LanthaScreen, Thermofisher Cat #PV4833). The purified ligand binding domain of human FXR tagged with GST (glutathiones-S-transferase) is incubated with a terbium labelled anti-GLT antibody and a fluorescein-labelled SRC2-2 peptide (LKEKHKILHRLLQDSSSPV (SEQ ID No.: 1)). Binding of FXR ligands to the FXR ligand binding domain promotes binding of the fluorescein-labelled SRC2-2 peptide. This causes a FRET signal between the terbium-labelled anti-GST antibody and the fluorescein-labelled SRC peptide which are both bound to the FXR ligand binding domain.Test compounds are dissolved in DMSO and a 3-fold serial dilution series is generated, then further diluted into assay buffer. The compounds are mixed with 5 nM GST-tagged FXR ligand binding domain, 5 nM Tb-labelled anti-GST antibody and 500 nM fluorcscein-labelled SRC2-2 peptide in a pH 7.4 buffer. The reaction is incubated at room temperature for 1 hour, then the FRET signal is measured as the ratio of the 520 nm/495 nm emission following excitation at 340 nm.
Measurement: EC50 = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 660.62, ALogP 6.67, HBA 8, HBD 1, PSA 118.81, QED 0.18
Compound (SMILES): Nc1cc(C(CCNC23CCC(c4ccccc4)(CC2)[C@H](O)C3)c2ccn(CCc3cccc(O)c3)n2)c2nn[nH]c2n1
InChIKey: SHINZIHSTQIJTL-HMWCFRPGSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: MPO Peroxidation Assay (Amplex Red Assay): MPO peroxidation activity was measured in 100 mM KPi (pH 7.4) by utilizing the non-fluorescent reagent Amplex Red (Invitrogen Cat. #A12222) which can be oxidized to the highly fluorescent resorufin. Amplex Red is oxidized by the peroxidase action of MPO to resorufin. Reactions were carried out in 50 μL total volume by adding a 25 μL mixture of 200 pM myeloperoxidase and 40 nM H2O2(Sigma #349887) to 100 nL inhibitor in 100% DMSO in a 384 well Perkin Elmer Optiplate. Enzyme and compound were preincubated for ten minutes at rt.After the ten minute preincubation, 25 μL of an Amplex Red mixture containing 200 μM Amplex Red and 10 mM H2O2 was added to the plate. Kinetic determinations were carried out immediately on a Perkin Elmer Envision (15 minute kinetic read, Ex: 535 nm, Em: 590 nm).IC50 values were calculated by determining the slope of the linear portion of the kinetic trace (180-540 secs), and using that calculated slope to determine % inhibition occurring at each concentration of inhibitor using the following equation:Y = A + B - A 1 + ( C / x ) Dwhere A=minimal Y value (activity level of inhibited sample), B=maximal Y value (activity level of uninhibited sample), C=Log IC50, D=Hill Slope, x=concentration of inhibitor.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 578.72, ALogP 4.21, HBA 9, HBD 5, PSA 150.79, QED 0.17
Compound (SMILES): COCCN(CCC(c1ccn(Cc2cccc(O)c2)n1)c1cc(N)nc2[nH]nnc12)C12CCC(c3ccccc3)(CC1)[C@H](O)C2
InChIKey: NKBAFYPBBNMNSJ-XQSHTXJCSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: MPO Peroxidation Assay (Amplex Red Assay): MPO peroxidation activity was measured in 100 mM KPi (pH 7.4) by utilizing the non-fluorescent reagent Amplex Red (Invitrogen Cat. #A12222) which can be oxidized to the highly fluorescent resorufin. Amplex Red is oxidized by the peroxidase action of MPO to resorufin. Reactions were carried out in 50 μL total volume by adding a 25 μL mixture of 200 pM myeloperoxidase and 40 nM H2O2(Sigma #349887) to 100 nL inhibitor in 100% DMSO in a 384 well Perkin Elmer Optiplate. Enzyme and compound were preincubated for ten minutes at rt.After the ten minute preincubation, 25 μL of an Amplex Red mixture containing 200 μM Amplex Red and 10 mM H2O2 was added to the plate. Kinetic determinations were carried out immediately on a Perkin Elmer Envision (15 minute kinetic read, Ex: 535 nm, Em: 590 nm).IC50 values were calculated by determining the slope of the linear portion of the kinetic trace (180-540 secs), and using that calculated slope to determine % inhibition occurring at each concentration of inhibitor using the following equation:Y = A + B - A 1 + ( C / x ) Dwhere A=minimal Y value (activity level of inhibited sample), B=maximal Y value (activity level of uninhibited sample), C=Log IC50, D=Hill Slope, x=concentration of inhibitor.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 622.77, ALogP 4.37, HBA 10, HBD 4, PSA 151.23, QED 0.16
Compound (SMILES): Nc1cc(C(CCN(CNC=O)C23CCC(c4ccccc4)(CC2)[C@H](O)C3)c2ccn(Cc3cccc(O)c3)n2)c2nn[nH]c2n1
InChIKey: WLGZKPBTLDVNEY-ZKJKZDHBSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: MPO Peroxidation Assay (Amplex Red Assay): MPO peroxidation activity was measured in 100 mM KPi (pH 7.4) by utilizing the non-fluorescent reagent Amplex Red (Invitrogen Cat. #A12222) which can be oxidized to the highly fluorescent resorufin. Amplex Red is oxidized by the peroxidase action of MPO to resorufin. Reactions were carried out in 50 μL total volume by adding a 25 μL mixture of 200 pM myeloperoxidase and 40 nM H2O2(Sigma #349887) to 100 nL inhibitor in 100% DMSO in a 384 well Perkin Elmer Optiplate. Enzyme and compound were preincubated for ten minutes at rt.After the ten minute preincubation, 25 μL of an Amplex Red mixture containing 200 μM Amplex Red and 10 mM H2O2 was added to the plate. Kinetic determinations were carried out immediately on a Perkin Elmer Envision (15 minute kinetic read, Ex: 535 nm, Em: 590 nm).IC50 values were calculated by determining the slope of the linear portion of the kinetic trace (180-540 secs), and using that calculated slope to determine % inhibition occurring at each concentration of inhibitor using the following equation:Y = A + B - A 1 + ( C / x ) Dwhere A=minimal Y value (activity level of inhibited sample), B=maximal Y value (activity level of uninhibited sample), C=Log IC50, D=Hill Slope, x=concentration of inhibitor.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 621.75, ALogP 3.43, HBA 10, HBD 5, PSA 171.1, QED 0.1
Compound (SMILES): O=C(O)[C@@H]1[C@@H]2CC[C@@H](CC2OCc2ccccc2)N1C(=O)C(c1ccccc1)c1ccccc1
InChIKey: BDWLJWPALGCSPZ-QUDVPHRHSA-N
Target: Type-2 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P50052
Assay: Biological Assay: Measurement of Inhibitory Activity on AT1 Receptor (AT4R)/AT2 Receptor (AT2R)Through the following steps, the inhibitory activity of the compound on AT1R/AT2R (IC50 value) was determined:1) An appropriate amount of 1×TLB (Tag-lite Buffer) was prepared and well mixed for use.2) The compound was diluted by 10 times with ddH2O or DMSO. The compound was then dilute to 4 times of the working concentration with 1×TLB and mixed well for use.3) 8600 nM Tag-lite angiotensin receptor red agonist was diluted to 12 nM (4×Kd) with 1×TLB.4) 5 ml 1×TLB was taken into a 15 ml centrifuge tube.5) After thawing 1 tube of Tb-labeled AT1R/AT2R cells in a 37° C. water bath, the cells were quickly transferred to the 1×TLB in step 4), mixed gently, and centrifuged at 1200 g for 5 minutes at room temperature.6) The supernatant was aspirated gently, and the cells were resuspended and mixed in 2.7 ml 1×TLB, and then placed at room temperature until use.7) 10 μl cells were added to all test wells, and 5 μl 4× working solution of the compound from step 2) was added to the corresponding test wells. 5 μl 4× Tag-lite angiotensin receptor red agonist well diluted in step 3) was added to all test wells.8) After leaving the reaction plate at room temperature for 1 h, data were measured and analyzed using Envision HTRF Reader, and the half inhibitory concentration (IC50) of the compound on AT1R/AT2R was calculated with the GraphPad Prism four-parameter equation.
Measurement: IC50 = 46.3 nM (pChEMBL 7.329999923706055)
Descriptors: MW 455.55, ALogP 4.87, HBA 3, HBD 1, PSA 66.84, QED 0.55
Compound (SMILES): O=C(O)[C@@H]1[C@@H]2CC[C@@H](CC2Oc2ccc([N+](=O)[O-])cc2)N1C(=O)C(c1ccccc1)c1ccccc1
InChIKey: PHEOIFAHGSIIBF-FURIKZCYSA-N
Target: Type-2 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P50052
Assay: Biological Assay: Measurement of Inhibitory Activity on AT1 Receptor (AT4R)/AT2 Receptor (AT2R)Through the following steps, the inhibitory activity of the compound on AT1R/AT2R (IC50 value) was determined:1) An appropriate amount of 1×TLB (Tag-lite Buffer) was prepared and well mixed for use.2) The compound was diluted by 10 times with ddH2O or DMSO. The compound was then dilute to 4 times of the working concentration with 1×TLB and mixed well for use.3) 8600 nM Tag-lite angiotensin receptor red agonist was diluted to 12 nM (4×Kd) with 1×TLB.4) 5 ml 1×TLB was taken into a 15 ml centrifuge tube.5) After thawing 1 tube of Tb-labeled AT1R/AT2R cells in a 37° C. water bath, the cells were quickly transferred to the 1×TLB in step 4), mixed gently, and centrifuged at 1200 g for 5 minutes at room temperature.6) The supernatant was aspirated gently, and the cells were resuspended and mixed in 2.7 ml 1×TLB, and then placed at room temperature until use.7) 10 μl cells were added to all test wells, and 5 μl 4× working solution of the compound from step 2) was added to the corresponding test wells. 5 μl 4× Tag-lite angiotensin receptor red agonist well diluted in step 3) was added to all test wells.8) After leaving the reaction plate at room temperature for 1 h, data were measured and analyzed using Envision HTRF Reader, and the half inhibitory concentration (IC50) of the compound on AT1R/AT2R was calculated with the GraphPad Prism four-parameter equation.
Measurement: IC50 = 561 nM (pChEMBL 6.25)
Descriptors: MW 486.52, ALogP 4.64, HBA 5, HBD 1, PSA 109.98, QED 0.38
Compound (SMILES): O=C(O)[C@@H]1[C@@H]2CC[C@@H](CC2OCc2cccc(Cl)c2)N1C(=O)C(c1ccccc1)c1ccccc1
InChIKey: QMYCZRJLUXBMFV-QUDVPHRHSA-N
Target: Type-2 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P50052
Assay: Biological Assay: Measurement of Inhibitory Activity on AT1 Receptor (AT4R)/AT2 Receptor (AT2R)Through the following steps, the inhibitory activity of the compound on AT1R/AT2R (IC50 value) was determined:1) An appropriate amount of 1×TLB (Tag-lite Buffer) was prepared and well mixed for use.2) The compound was diluted by 10 times with ddH2O or DMSO. The compound was then dilute to 4 times of the working concentration with 1×TLB and mixed well for use.3) 8600 nM Tag-lite angiotensin receptor red agonist was diluted to 12 nM (4×Kd) with 1×TLB.4) 5 ml 1×TLB was taken into a 15 ml centrifuge tube.5) After thawing 1 tube of Tb-labeled AT1R/AT2R cells in a 37° C. water bath, the cells were quickly transferred to the 1×TLB in step 4), mixed gently, and centrifuged at 1200 g for 5 minutes at room temperature.6) The supernatant was aspirated gently, and the cells were resuspended and mixed in 2.7 ml 1×TLB, and then placed at room temperature until use.7) 10 μl cells were added to all test wells, and 5 μl 4× working solution of the compound from step 2) was added to the corresponding test wells. 5 μl 4× Tag-lite angiotensin receptor red agonist well diluted in step 3) was added to all test wells.8) After leaving the reaction plate at room temperature for 1 h, data were measured and analyzed using Envision HTRF Reader, and the half inhibitory concentration (IC50) of the compound on AT1R/AT2R was calculated with the GraphPad Prism four-parameter equation.
Measurement: IC50 = 765 nM (pChEMBL 6.119999885559082)
Descriptors: MW 490, ALogP 5.52, HBA 3, HBD 1, PSA 66.84, QED 0.47
Compound (SMILES): O=C(O)[C@@H]1[C@@H]2CC[C@@H](CC2OCc2ccccc2Cl)N1C(=O)C(c1ccccc1)c1ccccc1
InChIKey: SIJMAKSIEUGZBG-JYVSNMONSA-N
Target: Type-2 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P50052
Assay: Biological Assay: Measurement of Inhibitory Activity on AT1 Receptor (AT4R)/AT2 Receptor (AT2R)Through the following steps, the inhibitory activity of the compound on AT1R/AT2R (IC50 value) was determined:1) An appropriate amount of 1×TLB (Tag-lite Buffer) was prepared and well mixed for use.2) The compound was diluted by 10 times with ddH2O or DMSO. The compound was then dilute to 4 times of the working concentration with 1×TLB and mixed well for use.3) 8600 nM Tag-lite angiotensin receptor red agonist was diluted to 12 nM (4×Kd) with 1×TLB.4) 5 ml 1×TLB was taken into a 15 ml centrifuge tube.5) After thawing 1 tube of Tb-labeled AT1R/AT2R cells in a 37° C. water bath, the cells were quickly transferred to the 1×TLB in step 4), mixed gently, and centrifuged at 1200 g for 5 minutes at room temperature.6) The supernatant was aspirated gently, and the cells were resuspended and mixed in 2.7 ml 1×TLB, and then placed at room temperature until use.7) 10 μl cells were added to all test wells, and 5 μl 4× working solution of the compound from step 2) was added to the corresponding test wells. 5 μl 4× Tag-lite angiotensin receptor red agonist well diluted in step 3) was added to all test wells.8) After leaving the reaction plate at room temperature for 1 h, data were measured and analyzed using Envision HTRF Reader, and the half inhibitory concentration (IC50) of the compound on AT1R/AT2R was calculated with the GraphPad Prism four-parameter equation.
Measurement: IC50 = 666 nM (pChEMBL 6.179999828338623)
Descriptors: MW 490, ALogP 5.52, HBA 3, HBD 1, PSA 66.84, QED 0.47
Compound (SMILES): CN1CC[C@]23CCCC[C@@H]2[C@@H]1Cc1ccc(O)cc13
InChIKey: JAQUASYNZVUNQP-HYVNUMGLSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Receptor Binding Assay: In vitro binding assays for the phencyclidine site of NMDA-type glutamate receptors, and for sigma-1 receptors, both of which are known to be bound by DM, were conducted by Sekisui Medical Co., Ltd. of Ibaraki, Japan. In these assays, DM acts as an antagonist at NMDA receptors, which are excitatory in their effects, thereby allowing DM to reduce, calm, and modulate unwanted neuronal activity in neuronal networks that are activated by glutamate agonist activity at NMDA receptors. DM acts as an agonist at sigma-1 receptors, which are inhibitory receptors, thereby allowing DM to reduce unwanted neuronal activity by a second mechanism.
Measurement: IC50 = 259 nM (pChEMBL 6.590000152587891)
Descriptors: MW 257.38, ALogP 3.08, HBA 2, HBD 1, PSA 23.47, QED 0.77
Compound (SMILES): Cc1ccc2c(c1)[C@@]13CCCC[C@@H]1[C@H](C2)N(C)CC3
InChIKey: KBEZZLAAKIIPFK-BPQIPLTHSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Receptor Binding Assay: In vitro binding assays for the phencyclidine site of NMDA-type glutamate receptors, and for sigma-1 receptors, both of which are known to be bound by DM, were conducted by Sekisui Medical Co., Ltd. of Ibaraki, Japan. In these assays, DM acts as an antagonist at NMDA receptors, which are excitatory in their effects, thereby allowing DM to reduce, calm, and modulate unwanted neuronal activity in neuronal networks that are activated by glutamate agonist activity at NMDA receptors. DM acts as an agonist at sigma-1 receptors, which are inhibitory receptors, thereby allowing DM to reduce unwanted neuronal activity by a second mechanism.
Measurement: IC50 = 527 nM (pChEMBL 6.28000020980835)
Descriptors: MW 255.41, ALogP 3.68, HBA 1, HBD 0, PSA 3.24, QED 0.68
Compound (SMILES): CN1CC[C@]23CCCCC2C1Cc1ccc(OCC(F)F)c(Br)c13
InChIKey: QORYGWRVEPVZNI-SVGDTCPJSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Receptor Binding Assay: In vitro binding assays for the phencyclidine site of NMDA-type glutamate receptors, and for sigma-1 receptors, both of which are known to be bound by DM, were conducted by Sekisui Medical Co., Ltd. of Ibaraki, Japan. In these assays, DM acts as an antagonist at NMDA receptors, which are excitatory in their effects, thereby allowing DM to reduce, calm, and modulate unwanted neuronal activity in neuronal networks that are activated by glutamate agonist activity at NMDA receptors. DM acts as an agonist at sigma-1 receptors, which are inhibitory receptors, thereby allowing DM to reduce unwanted neuronal activity by a second mechanism.
Measurement: IC50 = 21.8 nM (pChEMBL 7.659999847412109)
Descriptors: MW 400.31, ALogP 4.78, HBA 2, HBD 0, PSA 12.47, QED 0.72
Compound (SMILES): COc1cc(-c2c3c(nn2C)[C@H]2CCCC(C3)N2C(=O)c2nn(C)c3ncccc23)cc(F)c1F
InChIKey: IKMHRABILAXCIT-XPKAQORNSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: In Vitro Activity Assay: The assay used to measure the in vitro activity of MGL is adapted from the assay used for another serine hydrolase (FAAH) described in Wilson et al., 2003 (A high-throughput-compatible assay for determining the activity of fatty acid amide hydrolase. Wilson S J, Lovenberg T W, Barbier A J. Anal Biochem. 2003 Jul. 15; 318(2):270-5). The assay consists of combining endogenously expressed MGL from HeLa cells with test compounds, adding [glycerol-1,3-3H]-oleoyl glycerol, incubating for one hour, and then measuring the amount of cleaved [1,3-3H]-glycerol that passes through an activated carbon filter. The amount of cleaved, tritiated glycerol passing through the carbon filter is proportional to the activity of the MGL enzyme in a particular well/test condition. Standard conditions for this assay combine 300 nM [Glycerol-1,3-3H]-oleoyl glycerol with human MGL from HeLa cells and test compounds for one hour, after which the reaction is filtered through activated carbon and tritium is measured in the flow through. The test compound concentration in screening mode is 10 uM, while the highest compound concentration in IC50 assays is determined empirically.
Measurement: IC50 = 20.8 nM (pChEMBL 7.679999828338623)
Descriptors: MW 478.5, ALogP 3.95, HBA 7, HBD 0, PSA 78.07, QED 0.45
Compound (SMILES): CCOc1cc(-c2ccc(N3C[C@@H]4C[C@](C)(C3)[C@H]4Nc3ccc(OC)nc3)nc2)c2c(C#N)cnn2c1
InChIKey: JYZNSJOMZOUNDR-LVRGLSNDSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: RET Enzyme Assay: Compounds of Formula I were screened for their ability to inhibit wildtype and V804M mutant RET kinase using CisBio's HTRF® KinEASE-TK assay technology. Briefly, N-terminal GST tagged recombinant human RET cytoplasmic domain (aa 658-end) from Eurofins (0.25 nM RET; Catalog No. 14-570M) or N-terminal GST tagged recombinant human V804M mutant RET cytoplasmic domain (aa 658-end) from Millipore (0.25 nM enzyme; Catalog No. 14-760) was incubated with 250 nM TK-substrate biotin (CisBio, part of Catalog No. 62TK0PEC) and 1 mM ATP along with test compound in a buffer consisting of 25 mM HEPES pH 7.4, 10 mM MgCl2, 0.01% Triton X-100, and 2% DMSO in a volume of 8 μL. Compounds were typically prepared in a threefold serial dilution in DMSO and added to the assay to give the appropriate final concentration. After a 30-minute incubation at 22° C., the reaction was quenched by adding 8 μL of quench solution containing 31.25 nM Sa-XL665 and 1× TK-ab-Cryptate in HTRF detection buffer (all from CisBio, part of Cat. No. 62TK0PEC). After a 1 hour incubation at 22° C., the extent of reaction was determined using a PerkinElmer EnVision multimode plate reader via HTRF dual wavelength detection, and the percent of control (POC) was calculated using a ratiometric emission factor. 100 POC was determined using no test compounds and 0 POC was determined using pre-quenched control reactions. The POC values were fit to a 4 parameter logistic curve, and the IC50 is defined as the concentration of inhibitor at which the POC equals 50 for the fitted curve. The IC50.
Measurement: IC50 = 69.9 nM (pChEMBL 7.159999847412109)
Descriptors: MW 495.59, ALogP 4.4, HBA 9, HBD 1, PSA 100.6, QED 0.4
Compound (SMILES): N#CCCN(C(=O)CCl)c1ccc2c(c1)OCCN2CC(=O)N1CCC(C(=O)Nc2ccc(C(=O)NCCCCCCC(=O)NO)cc2)CC1.O=C(O)C(F)(F)F
InChIKey: CHCZCWWFRWSTTR-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using ZMAL (Z-(Ac)Lys-AMC) as substrate incubated for 90 mins by fluorescence based assay
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 710.23, ALogP 3.43, HBA 9, HBD 4, PSA 184.41, QED 0.09
Compound (SMILES): S=C(N/N=C/c1ccccc1)Nc1c2ccccc2nc2ccccc12
InChIKey: FWJRWXDDRODYHP-HYARGMPZSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 2470 nM (pChEMBL 5.610000133514404)
Descriptors: MW 356.45, ALogP 4.71, HBA 3, HBD 2, PSA 49.31, QED 0.24
Compound (SMILES): CC(C)C(=O)Nc1ccnc(C#Cc2ccc(Nc3ncc(-c4ccccn4)c(N[C@H]4CC[C@H](O)CC4)n3)cc2)c1
InChIKey: VAOGIOMRWIEXDW-JIBACQESSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin)
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 547.66, ALogP 5.39, HBA 8, HBD 4, PSA 124.95, QED 0.23
Compound (SMILES): CS(=O)(=O)N1CCC(N[C@H]2CCCOc3c2nn(-c2ccccc2Cl)c3-c2ccc(Cl)cc2)CC1
InChIKey: MCMCBMDPIAFAGY-NRFANRHFSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP-55940 from human CB1R stably transfected in HEK293 cell membrane by beta-counter analysis
Measurement: Ki = 9.09 nM (pChEMBL 8.039999961853027)
Descriptors: MW 535.5, ALogP 5.07, HBA 6, HBD 1, PSA 76.46, QED 0.49
Compound (SMILES): O=S(=O)(F)N1CCC(c2cc(-c3ccnc4[nH]ccc34)[nH]n2)CC1
InChIKey: APMLNYNBZGITSU-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of ROCK2 (unknown origin) incubated for 40 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 329 nM (pChEMBL 6.480000019073486)
Descriptors: MW 349.39, ALogP 2.35, HBA 4, HBD 2, PSA 94.74, QED 0.71
Compound (SMILES): O=C(C1CCC1)N1CCC(c2cc(-c3ccnc4[nH]ccc34)[nH]n2)CC1
InChIKey: HJVLEZFVQDNSHT-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of ROCK2 (unknown origin) incubated for 40 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 1054 nM (pChEMBL 5.980000019073486)
Descriptors: MW 349.44, ALogP 3.46, HBA 3, HBD 2, PSA 77.67, QED 0.76
Compound (SMILES): Cc1c(N2CCCC2=O)cccc1S(=O)(=O)N[C@@H](CNC(=O)c1ccc(Cl)s1)C(=O)OCCS(C)(=O)=O
InChIKey: CJXHOHJDCJCNHI-HNNXBMFYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human factor Xa in Tris buffer using Boc-Ile-Glu-GlyArg-AMC as substrate preincubated for 30 mins followed by substrate addition measured after 30 mins
Measurement: IC50 = 0.49 nM (pChEMBL 9.3100004196167)
Descriptors: MW 592.12, ALogP 1.5, HBA 9, HBD 2, PSA 156.02, QED 0.37
Compound (SMILES): CN(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc3nonc3nc2Nc2ccc(Cl)cc2Cl)c1O
InChIKey: BFLDLMVRUDWWSV-UHFFFAOYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Antagonist activity at CCR2 in human U87.CD4.CCR2 cells assessed as inhibition of CCL2-induced intracellular calcium flux preincubated with compound for 1 mins and measured after 10 mins by FLIPR calcium-6 assay
Measurement: IC50 = 30970 nM (pChEMBL 4.510000228881836)
Descriptors: MW 530.78, ALogP 4.42, HBA 10, HBD 3, PSA 146.37, QED 0.31
Compound (SMILES): CN(C)[C@H]1CN(c2ccc(-n3cnc(Nc4cnc(C#N)cn4)c3)cc2)C[C@H]1F
InChIKey: PBVZVDPWVOBICR-MSOLQXFVSA-N
Target: Serine/threonine-protein kinase Chk2 (SINGLE PROTEIN), Homo sapiens
UniProt: O96017
Assay: Inhibition of N-terminal GST-fused human full length CHK2 (1 to 543 residues) expressed in baculovirus-infected Sf21 cells using STK1 S1 as substrate preincubated for 30 mins in presence of ATP followed by MgCl2 addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 3190 nM (pChEMBL 5.5)
Descriptors: MW 392.44, ALogP 2.37, HBA 8, HBD 1, PSA 85.9, QED 0.71
Compound (SMILES): Cc1c([C@@H](C)Nc2nc3c(c4cc(=O)n(C5CCOCC5)cc24)CC(C)(O)CC3)cccc1C(F)(F)F
InChIKey: GPOJYJQKHGETEU-MOJDWNGGSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Binding affinity to recombinant human His10-tagged SOS1 (564 to 1049 residues) assessed as inhibition of GST-tagged human KRAS G12C mutant (1 to 169 residues) interaction with SOS1 preincubated for 15 mins followed by KRAS addition and measured after 2 hrs by FRET assay
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 515.58, ALogP 5.49, HBA 6, HBD 2, PSA 76.38, QED 0.48
Compound (SMILES): C[C@H](Nc1ncnc2[nH]ccc12)C1CC1
InChIKey: XQRISGIOBNQKET-ZETCQYMHSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of LRRK2 G2019S mutant (unknown origin) purified from baculovirus infected Sf9 cells assessed as autophosphorylation using RLGAWRFYTLRRARQGNTKQ peptide substrate incubated for 30 mins by liquid scintillation count analysis
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 202.26, ALogP 2.17, HBA 3, HBD 2, PSA 53.6, QED 0.8
Compound (SMILES): O=C(Nc1ccc(C(F)(F)F)cc1)c1nc(-c2ccc(F)cc2)cs1
InChIKey: RXMZAXFKOIATNR-UHFFFAOYSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of human recombinant CYP1A1 using 7-ethoxyresorufin as substrate incubated under dark condition for 15 mins in presence of NADPH by EROD fluorescence assay
Measurement: IC50 = 346.3 nM (pChEMBL 6.460000038146973)
Descriptors: MW 366.34, ALogP 5.22, HBA 3, HBD 1, PSA 41.99, QED 0.65
Compound (SMILES): O=C(NC1CC1)c1cccc(C#Cc2ccc(Nc3ncc(-c4ccccn4)c(N[C@H]4CC[C@H](O)CC4)n3)cc2)c1
InChIKey: RABLJBYNPYCYJV-FCMXBYMOSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin)
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 544.66, ALogP 5.29, HBA 7, HBD 4, PSA 112.06, QED 0.23
Compound (SMILES): CCn1c2c(c(=O)[nH]c1=O)C1C(=C(C)N2)C(=O)OCc2ccccc2OCCOc2cc1ccc2C
InChIKey: YEMAZXQMCPPNBM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to N-terminal hexa histidine-tagged human BRD4 BD1 extracted from Escherichia coli BL21 (DE3) cells assessed as inhibition constant incubated for 1 hrs by fluorescence polarization assay
Measurement: Ki = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 489.53, ALogP 3.21, HBA 8, HBD 2, PSA 111.65, QED 0.51
Compound (SMILES): CCOC(=O)/C=C/c1c(-c2c(-c3cccc(C)n3)nn3c2CCC3)ccc2ncnn12
InChIKey: DWHMCMQAVFIWGA-ZRDIBKRKSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of p38alpha (unknown origin) measured after 40 mins in presence of [gamma-33P]ATP by microbeta liquid scintillation counting analysis
Measurement: IC50 = 5910 nM (pChEMBL 5.230000019073486)
Descriptors: MW 414.47, ALogP 3.49, HBA 8, HBD 0, PSA 87.2, QED 0.37