lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCC(=Cc2nc3cc(Cl)ccc3[nH]2)CC1
InChIKey: LZFIKFXIHTZOJR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: Displacement of [3H]granisetron from human 5-HT3AR expressed in HEK293 cells after 24 hrs by liquid scintillation counting
Measurement: Ki = 1.585 nM (pChEMBL 8.800000190734863)
Descriptors: MW 261.76, ALogP 3.33, HBA 2, HBD 1, PSA 31.92, QED 0.85
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: QIXXUKXLULSIND-REMOFRLVSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst2 receptor in CCL39 cells after 2 hrs by autoradiography
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 1614.87
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: QIXXUKXLULSIND-TTZRXDBLSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst2 receptor in CCL39 cells after 2 hrs by autoradiography
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 1614.87
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: PPMRXEMNCQTEFU-DQMVLKBGSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst2 receptor in CCL39 cells after 2 hrs by autoradiography
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 1648.93
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: PPMRXEMNCQTEFU-RPZSHQLJSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst2 receptor in CCL39 cells after 2 hrs by autoradiography
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 1648.93
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2cn(Cc3ccccc3)cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: PCOKLAQIKLJNCC-TUQJLTHMSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst2 receptor in CCL39 cells after 2 hrs by autoradiography
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1678.96
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2cn(Cc3ccccc3)cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: PCOKLAQIKLJNCC-PPQOTRBLSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst2 receptor in CCL39 cells after 2 hrs by autoradiography
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 1678.96
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: PJRZZHKHLDKTKL-VJLATZRLSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Partial agonist activity at human sst3 receptor expressed in CCL39 cells after 5 hrs by luciferase reporter gene assay
Measurement: EC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 1079.32
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: ZWDCQOWLWNRGRH-LWNGEPAASA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst2 receptor in CCL39 cells after 2 hrs by autoradiography
Measurement: IC50 = 173 nM (pChEMBL 6.760000228881836)
Descriptors: MW 1090.34
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2cn(Cc3ccccc3)cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: QGPLCSNQORHDTQ-UVDDJNJYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst2 receptor in CCL39 cells after 2 hrs by autoradiography
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1120.37
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2cn(Cc3ccccc3)cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: QGPLCSNQORHDTQ-VQFDOSOCSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst2 receptor in CCL39 cells after 2 hrs by autoradiography
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1120.37
Compound (SMILES): COc1cc2ncnc(Nc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: RECOBLXZEHQJJF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 462.51, ALogP 5.32, HBA 8, HBD 3, PSA 123.43, QED 0.35
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: FJUMAPNPNSYMAU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 463.49, ALogP 5.37, HBA 8, HBD 2, PSA 120.63, QED 0.39
Compound (SMILES): COc1cc2ncnc(Sc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: FFLVHWGDEYLFKE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 479.56, ALogP 5.73, HBA 8, HBD 2, PSA 111.4, QED 0.34
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cccc(C(F)(F)F)c4)c3)c2cc1OC
InChIKey: QPJTXOPHNPRKOS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 1664 nM (pChEMBL 5.78000020980835)
Descriptors: MW 484.43, ALogP 6.1, HBA 6, HBD 2, PSA 94.6, QED 0.34
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cccc(C(C)(C)C)c4)c3)c2cc1OC
InChIKey: XLDWUSQMDJOMMX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 333 nM (pChEMBL 6.480000019073486)
Descriptors: MW 472.55, ALogP 6.38, HBA 6, HBD 2, PSA 94.6, QED 0.34
Compound (SMILES): COc1cccc(NC(=O)Nc2cccc(Oc3ncnc4cc(OC)c(OC)cc34)c2)c1
InChIKey: ILRHFINBZIHVAO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 446.46, ALogP 5.09, HBA 7, HBD 2, PSA 103.83, QED 0.41
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4ccc(Cl)cc4)c3)c2cc1OC
InChIKey: SUAVWHXDRSHRAU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 1850 nM (pChEMBL 5.730000019073486)
Descriptors: MW 450.88, ALogP 5.74, HBA 6, HBD 2, PSA 94.6, QED 0.39
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4ccc(C(C)(C)C)cc4)c3)c2cc1OC
InChIKey: BWKRBEKNGFHQLO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 472.55, ALogP 6.38, HBA 6, HBD 2, PSA 94.6, QED 0.34
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4ccc(Cl)c(C(F)(F)F)c4)c3)c2cc1OC
InChIKey: LFWLHYKPWIJSBE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 696 nM (pChEMBL 6.159999847412109)
Descriptors: MW 518.88, ALogP 6.76, HBA 6, HBD 2, PSA 94.6, QED 0.29
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3C)c2cc1OC
InChIKey: QLLMCJODYDQMKE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 179 nM (pChEMBL 6.75)
Descriptors: MW 477.52, ALogP 5.68, HBA 8, HBD 2, PSA 120.63, QED 0.36
Compound (SMILES): COc1cc2ncnc(Oc3ccc(F)c(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: BFGHWVXEBAHITM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 481.48, ALogP 5.51, HBA 8, HBD 2, PSA 120.63, QED 0.37
Compound (SMILES): COc1cc2ncnc(Oc3ccc(Cl)c(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: SOSHULPZORWFMN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 497.94, ALogP 6.02, HBA 8, HBD 2, PSA 120.63, QED 0.33
Compound (SMILES): CN1C(=O)C(c2cccc(-c3cncnc3)c2)(c2cnn(C)c2)N=C1N
InChIKey: CORGHEXKCNZSJU-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 347.38, ALogP 0.91, HBA 7, HBD 1, PSA 102.29, QED 0.76
Compound (SMILES): CCn1cc(C2(c3cccc(-c4cncnc4)c3)N=C(N)N(C)C2=O)cn1
InChIKey: DNDFMOOQRXKYQL-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 1470 nM (pChEMBL 5.829999923706055)
Descriptors: MW 361.41, ALogP 1.39, HBA 7, HBD 1, PSA 102.29, QED 0.76
Compound (SMILES): CCn1cc(C2(c3ccc(F)c(-c4cncnc4)c3)N=C(N)N(C)C2=O)cn1
InChIKey: QFKPRVADZPYBNW-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 379.4, ALogP 1.53, HBA 7, HBD 1, PSA 102.29, QED 0.74
Compound (SMILES): CN1C(=O)C(c2ccc(F)c(-c3cncnc3)c2)(c2cnn(CC(F)(F)F)c2)N=C1N
InChIKey: FCWFCMGXLUBIQD-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 433.37, ALogP 2.07, HBA 7, HBD 1, PSA 102.29, QED 0.64
Compound (SMILES): CC(C)n1cc(C2(c3ccc(F)c(-c4cncnc4)c3)N=C(N)N(C)C2=O)cn1
InChIKey: VGIXLLYAMZATOQ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 393.43, ALogP 2.09, HBA 7, HBD 1, PSA 102.29, QED 0.73
Compound (SMILES): CC(C)Cn1cc(C2(c3cccc(-c4cncnc4)c3)N=C(N)N(C)C2=O)cn1
InChIKey: GJCACXYIYRCVKX-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 389.46, ALogP 2.03, HBA 7, HBD 1, PSA 102.29, QED 0.72
Compound (SMILES): CC(C)CCn1cc(C2(c3cccc(-c4cncnc4)c3)N=C(N)N(C)C2=O)cn1
InChIKey: DUYKHVPWTFUMKA-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 by FRET assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 403.49, ALogP 2.42, HBA 7, HBD 1, PSA 102.29, QED 0.68
Compound (SMILES): CN1C(=O)C(c2cccc(-c3cncnc3)c2)(c2cnn(CCC(C)(C)C)c2)N=C1N
InChIKey: AMYWYRFRJYJRAM-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 417.52, ALogP 2.81, HBA 7, HBD 1, PSA 102.29, QED 0.69
Compound (SMILES): CCCCn1cc(C2(c3cccc(-c4cncnc4)c3)N=C(N)N(C)C2=O)cn1
InChIKey: CRGYAUNBGVFARQ-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 389.46, ALogP 2.17, HBA 7, HBD 1, PSA 102.29, QED 0.7
Compound (SMILES): CN1C(=O)C(c2cccc(-c3cncnc3)c2)(c2cnn(C3CCCC3)c2)N=C1N
InChIKey: RSBLHFREHLCSDX-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 401.47, ALogP 2.49, HBA 7, HBD 1, PSA 102.29, QED 0.72
Compound (SMILES): CN1C(=O)C(c2cccc(-c3cncnc3)c2)(c2cnn(CCC3CCCCC3)c2)N=C1N
InChIKey: IMPSJODCGOEHNO-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 443.56, ALogP 3.34, HBA 7, HBD 1, PSA 102.29, QED 0.63
Compound (SMILES): CCn1cc(C2(c3cccc(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cn1
InChIKey: IKJXVRPWMOVIMY-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 378.41, ALogP 2.13, HBA 6, HBD 1, PSA 89.4, QED 0.7
Compound (SMILES): CCn1cc([C@]2(c3cccc(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cn1
InChIKey: IKJXVRPWMOVIMY-FQEVSTJZSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 378.41, ALogP 2.13, HBA 6, HBD 1, PSA 89.4, QED 0.7
Compound (SMILES): Cc1cccc(Oc2ccc3c4c(cccc24)C2=NC(=O)C(C#N)=C23)c1
InChIKey: JECDGNOBGBDIPY-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FAM-Bid peptide from human Mcl-1 after 30 mins by competitive fluorescence polarization assay
Measurement: Ki = 445 nM (pChEMBL 6.349999904632568)
Descriptors: MW 336.35, ALogP 4.56, HBA 3, HBD 0, PSA 62.45, QED 0.69
Compound (SMILES): Cc1ccccc1Oc1ccc2c3c(cccc13)C1=NC(=O)C(C#N)=C12
InChIKey: WJGYEKOJLFTYIV-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FAM-Bid peptide from human Mcl-1 after 30 mins by competitive fluorescence polarization assay
Measurement: Ki = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 336.35, ALogP 4.56, HBA 3, HBD 0, PSA 62.45, QED 0.69
Compound (SMILES): COc1ccccc1Oc1ccc2c3c(cccc13)C1=NC(=O)C(C#N)=C12
InChIKey: PRNJUJSNFAYRNO-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FAM-Bid peptide from human Mcl-1 after 30 mins by competitive fluorescence polarization assay
Measurement: Ki = 149 nM (pChEMBL 6.829999923706055)
Descriptors: MW 352.35, ALogP 4.26, HBA 4, HBD 0, PSA 71.68, QED 0.71
Compound (SMILES): COc1cccc(Oc2ccc3c4c(cccc24)C2=NC(=O)C(C#N)=C23)c1
InChIKey: DJPQAPIYCYUTLR-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FAM-Bid peptide from human Mcl-1 after 30 mins by competitive fluorescence polarization assay
Measurement: Ki = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 352.35, ALogP 4.26, HBA 4, HBD 0, PSA 71.68, QED 0.71
Compound (SMILES): CCC(C)c1ccc(Oc2ccc3c4c(cccc24)C2=NC(=O)C(C#N)=C23)cc1
InChIKey: VTYCCCCZIPADRN-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FAM-Bid peptide from human Mcl-1 after 30 mins by competitive fluorescence polarization assay
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 378.43, ALogP 5.77, HBA 3, HBD 0, PSA 62.45, QED 0.58
Compound (SMILES): Cc1cccc(-c2nn(CC(=O)Nc3ccccc3)cc2-c2ccc3nccnc3c2)n1
InChIKey: SICGTEGXKUZSHU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of human recombinant p38alpha expressed in Escherichia coli using ATF2 as substrate by radiometric kinase assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 420.48, ALogP 4.5, HBA 6, HBD 1, PSA 85.59, QED 0.45
Compound (SMILES): Cc1cccc(-c2nn(CC(=O)Nc3ccccc3)cc2-c2ccc3nc(C)c(C)nc3c2)n1
InChIKey: STWGGWFROPAXHA-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of human recombinant p38alpha expressed in Escherichia coli using ATF2 as substrate by radiometric kinase assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 448.53, ALogP 5.12, HBA 6, HBD 1, PSA 85.59, QED 0.4
Compound (SMILES): c1nc(CC2CCCCC2)c[nH]1
InChIKey: RWBFCYZFACUBIZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: Displacement of [3H]granisetron from human 5-HT3AR expressed in HEK293 cells after 24 hrs by liquid scintillation counting
Measurement: Ki = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 164.25, ALogP 2.53, HBA 1, HBD 1, PSA 28.68, QED 0.71
Compound (SMILES): CN(C)[C@H]1CC[C@@H](c2ccc(OCCCN3CCCCC3)cc2)CC1
InChIKey: NBCFVKKQKAXINS-TYKWCNGQSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 344.54, ALogP 4.53, HBA 3, HBD 0, PSA 15.71, QED 0.68
Compound (SMILES): CN(C)[C@H]1CC[C@H](c2ccc(OCCCN3CCCCC3)cc2)CC1
InChIKey: NBCFVKKQKAXINS-XUTJKUGGSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 344.54, ALogP 4.53, HBA 3, HBD 0, PSA 15.71, QED 0.68
Compound (SMILES): c1cc([C@H]2CC[C@H](N3CCC3)CC2)ccc1OCCCN1CCCCC1
InChIKey: BUPDKQVYUKWVSM-AQYVVDRMSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 356.55, ALogP 4.67, HBA 3, HBD 0, PSA 15.71, QED 0.66
Compound (SMILES): c1cc([C@H]2CC[C@@H](N3CCCC3)CC2)ccc1OCCCN1CCCCC1
InChIKey: IIGOTHGDDVVXRO-DKXQDJALSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 370.58, ALogP 5.06, HBA 3, HBD 0, PSA 15.71, QED 0.62
Compound (SMILES): c1cc([C@H]2CC[C@H](N3CCCC3)CC2)ccc1OCCCN1CCCCC1
InChIKey: IIGOTHGDDVVXRO-AFARHQOCSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 370.58, ALogP 5.06, HBA 3, HBD 0, PSA 15.71, QED 0.62
Compound (SMILES): c1cc([C@H]2CC[C@H](N3CCCCC3)CC2)ccc1OCCCN1CCCCC1
InChIKey: DQDIOQCBDIFEQD-HCGLCNNCSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.64 nM (pChEMBL 9.1899995803833)
Descriptors: MW 384.61, ALogP 5.45, HBA 3, HBD 0, PSA 15.71, QED 0.58
Compound (SMILES): CN1CCN([C@H]2CC[C@H](c3ccc(OCCCN4CCCCC4)cc3)CC2)CC1
InChIKey: CAGJHEKGANXSNK-HCGLCNNCSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.32 nM (pChEMBL 9.489999771118164)
Descriptors: MW 399.62, ALogP 4.22, HBA 4, HBD 0, PSA 18.95, QED 0.64
Compound (SMILES): c1cc([C@H]2CC[C@H](N3CCOCC3)CC2)ccc1OCCCN1CCCCC1
InChIKey: NFMCJKWXWBIFGH-AFARHQOCSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 386.58, ALogP 4.3, HBA 4, HBD 0, PSA 24.94, QED 0.65
Compound (SMILES): c1ccc2c(c1)CN([C@H]1CC[C@H](c3ccc(OCCCN4CCCCC4)cc3)CC1)C2
InChIKey: IEPREURIPCPAKP-JIBACQESSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 418.63, ALogP 5.98, HBA 3, HBD 0, PSA 15.71, QED 0.51
Compound (SMILES): c1ccc(CN[C@H]2CC[C@H](c3ccc(OCCCN4CCCCC4)cc3)CC2)cc1
InChIKey: MYSZKGRXICYNIZ-YOCNBXQISA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P58406
Assay: Displacement of [125I]Iodoproxyfan from mouse brain cortex histamine H3 receptor after 60 mins
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 406.61, ALogP 5.76, HBA 3, HBD 1, PSA 24.5, QED 0.54
Compound (SMILES): CCCCN[C@H]1CC[C@@H](c2ccc(OCCCN3CCCCC3)cc2)CC1
InChIKey: YSFJQETUBNXLQX-DKXQDJALSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.53 nM (pChEMBL 9.279999732971191)
Descriptors: MW 372.6, ALogP 5.36, HBA 3, HBD 1, PSA 24.5, QED 0.56
Compound (SMILES): CCCCN[C@H]1CC[C@H](c2ccc(OCCCN3CCCCC3)cc2)CC1
InChIKey: YSFJQETUBNXLQX-AFARHQOCSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.64 nM (pChEMBL 9.1899995803833)
Descriptors: MW 372.6, ALogP 5.36, HBA 3, HBD 1, PSA 24.5, QED 0.56
Compound (SMILES): Cc1ccc(C)c(-c2ccc(C(=O)Nc3c(C)cccc3C)s2)c1
InChIKey: GEJJRBDCCFHTMM-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Antagonist activity at S1P2 receptor
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 335.47, ALogP 5.9, HBA 2, HBD 1, PSA 29.1, QED 0.63
Compound (SMILES): COc1ccc2nc(-c3ccc(OCC(O)CNC(C)C)cc3)n(C)c(=O)c2c1
InChIKey: RNFBBRXRAZCIBZ-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [125I]-Iodopindolol from beta2-adrenergic receptor after 1.5 hrs by liquid scintillation counting
Measurement: Ki = 7700 nM (pChEMBL 5.110000133514404)
Descriptors: MW 397.48, ALogP 2.35, HBA 7, HBD 2, PSA 85.61, QED 0.61
Compound (SMILES): COc1ccc2nc(-c3ccc(OCC(O)CNC(C)CF)cc3)n(C)c(=O)c2c1
InChIKey: YZOOQGDAWJWLBX-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [125I]-Iodopindolol from beta2-adrenergic receptor after 1.5 hrs by liquid scintillation counting
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 415.47, ALogP 2.3, HBA 7, HBD 2, PSA 85.61, QED 0.56
Compound (SMILES): COc1ccc2nc(-c3ccc(OC[C@@H](O)CNC(C)CF)cc3)n(C)c(=O)c2c1
InChIKey: YZOOQGDAWJWLBX-WMCAAGNKSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [125I]-Iodopindolol from beta2-adrenergic receptor after 1.5 hrs by liquid scintillation counting
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 415.47, ALogP 2.3, HBA 7, HBD 2, PSA 85.61, QED 0.56
Compound (SMILES): CCCCCCCCCC(=O)N(CCN(C)C)CC1(C)Cc2ccccc2C(=O)N1
InChIKey: WGLUNLJVYNJMBU-UHFFFAOYSA-N
Target: G-protein coupled receptor homolog US28 (SINGLE PROTEIN), Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5)
UniProt: P69332
Assay: Allosteric modulatory activity at FLAG-tagged wild type human cytomegalovirus US28 receptor expressed in HEK293T cells by PathDetectElk1 assay
Measurement: EC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 415.62, ALogP 4.26, HBA 3, HBD 1, PSA 52.65, QED 0.49
Compound (SMILES): CC1(CO)Cc2ccccc2C(=O)N1c1ccccc1
InChIKey: MVUSOTSFFHMLDG-UHFFFAOYSA-N
Target: G-protein coupled receptor homolog US28 (SINGLE PROTEIN), Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5)
UniProt: P69332
Assay: Allosteric modulatory activity at FLAG-tagged wild type human cytomegalovirus US28 receptor expressed in HEK293T cells by PathDetectElk1 assay
Measurement: EC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 267.33, ALogP 2.64, HBA 2, HBD 1, PSA 40.54, QED 0.91
Compound (SMILES): CC1(CCO)Cc2ccccc2C(=O)N1c1ccccc1
InChIKey: CFGKUTDIZRYWRK-UHFFFAOYSA-N
Target: G-protein coupled receptor homolog US28 (SINGLE PROTEIN), Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5)
UniProt: P69332
Assay: Allosteric modulatory activity at FLAG-tagged wild type human cytomegalovirus US28 receptor expressed in HEK293T cells by PathDetectElk1 assay
Measurement: EC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 281.36, ALogP 3.03, HBA 2, HBD 1, PSA 40.54, QED 0.94
Compound (SMILES): CC1(COC(=O)Cc2ccccc2)Cc2ccccc2CN1C(=O)Cc1ccccc1
InChIKey: YPOSMQPBVIXZBM-UHFFFAOYSA-N
Target: G-protein coupled receptor homolog US28 (SINGLE PROTEIN), Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5)
UniProt: P69332
Assay: Allosteric modulatory activity at FLAG-tagged wild type human cytomegalovirus US28 receptor expressed in HEK293T cells by PathDetectElk1 assay
Measurement: EC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 413.52, ALogP 4.36, HBA 3, HBD 0, PSA 46.61, QED 0.56
Compound (SMILES): COc1cc2ncnc(Oc3cc(NC(=O)Nc4cc(C(C)(C)C)on4)ccc3F)c2cc1OC
InChIKey: OGUYROQAJPQEKG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 481.48, ALogP 5.51, HBA 8, HBD 2, PSA 120.63, QED 0.37
Compound (SMILES): COc1cc2ncnc(Oc3cc(NC(=O)Nc4cc(C(C)(C)C)on4)c(F)cc3F)c2cc1OC
InChIKey: SFLLFLVJFIUHDF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 499.47, ALogP 5.65, HBA 8, HBD 2, PSA 120.63, QED 0.35
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1O
InChIKey: VNEQWXQWPCTJQW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 449.47, ALogP 5.07, HBA 8, HBD 3, PSA 131.63, QED 0.38
Compound (SMILES): CCOc1cc2c(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)ncnc2cc1OC
InChIKey: AKMAIIKLSOGYGK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 477.52, ALogP 5.76, HBA 8, HBD 2, PSA 120.63, QED 0.34
Compound (SMILES): COCCOc1cc2c(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)ncnc2cc1OC
InChIKey: XKLFSXPPAPEOGH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 507.55, ALogP 5.39, HBA 9, HBD 2, PSA 129.86, QED 0.29
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OCCN1CCOCC1
InChIKey: UQEPJKKNAAEZLH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 562.63, ALogP 5.07, HBA 10, HBD 2, PSA 133.1, QED 0.28
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OCCCN1CCOCC1
InChIKey: NGUMRLVFPOPNSX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 576.65, ALogP 5.46, HBA 10, HBD 2, PSA 133.1, QED 0.23
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OCCN1CCCCC1
InChIKey: QPBHVADABCSTRU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 293 nM (pChEMBL 6.53000020980835)
Descriptors: MW 560.66, ALogP 6.22, HBA 9, HBD 2, PSA 123.87, QED 0.25
Compound (SMILES): COc1cc2c(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)ncnc2cc1O
InChIKey: VDHMQOXOGNLSNW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 449.47, ALogP 5.07, HBA 8, HBD 3, PSA 131.63, QED 0.38
Compound (SMILES): CCOc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: KYTCFLQYKXNBGM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd > 1000 nM (pChEMBL 6)
Descriptors: MW 477.52, ALogP 5.76, HBA 8, HBD 2, PSA 120.63, QED 0.34
Compound (SMILES): COCCOc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: HUPBPZKRSLMDLD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 507.55, ALogP 5.39, HBA 9, HBD 2, PSA 129.86, QED 0.29
Compound (SMILES): COc1cc2c(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)ncnc2cc1OCCN1CCOCC1
InChIKey: GTDRCAMYCRTQHC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 165 nM (pChEMBL 6.78000020980835)
Descriptors: MW 562.63, ALogP 5.07, HBA 10, HBD 2, PSA 133.1, QED 0.28
Compound (SMILES): COc1cc2c(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)ncnc2cc1OCCCN1CCOCC1
InChIKey: JSMHVUFIIHPEDP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 576.65, ALogP 5.46, HBA 10, HBD 2, PSA 133.1, QED 0.23
Compound (SMILES): CCn1cc([C@@]2(c3cccc(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cn1
InChIKey: IKJXVRPWMOVIMY-HXUWFJFHSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 378.41, ALogP 2.13, HBA 6, HBD 1, PSA 89.4, QED 0.7
Compound (SMILES): CCn1cc(C2(c3ccc(F)c(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cn1
InChIKey: XLKFXPAKZSTNHX-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 396.4, ALogP 2.27, HBA 6, HBD 1, PSA 89.4, QED 0.69
Compound (SMILES): CN1C(=O)C(c2cccc(-c3cccnc3F)c2)(c2cnn(CCF)c2)N=C1N
InChIKey: WTRPZTMQYKOUOO-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 396.4, ALogP 2.08, HBA 6, HBD 1, PSA 89.4, QED 0.67
Compound (SMILES): CN1C(=O)[C@](c2cccc(-c3cccnc3F)c2)(c2cnn(CC(F)(F)F)c2)N=C1N
InChIKey: FLYFOUIVIYZLRH-FQEVSTJZSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 432.38, ALogP 2.68, HBA 6, HBD 1, PSA 89.4, QED 0.51
Compound (SMILES): CC(C)n1cc(C2(c3ccc(F)c(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cn1
InChIKey: HNEPKJNWZLGKMM-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 410.43, ALogP 2.83, HBA 6, HBD 1, PSA 89.4, QED 0.67
Compound (SMILES): CC(C)Cn1cc(C2(c3cccc(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cn1
InChIKey: FCODAEYPNNQDQH-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 406.47, ALogP 2.77, HBA 6, HBD 1, PSA 89.4, QED 0.66
Compound (SMILES): CC(C)CCn1cc(C2(c3cccc(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cn1
InChIKey: KBZBWMIJRAOKSO-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 420.49, ALogP 3.16, HBA 6, HBD 1, PSA 89.4, QED 0.62
Compound (SMILES): CN1C(=O)C(c2cccc(-c3cccnc3F)c2)(c2cnn(CCC(C)(C)C)c2)N=C1N
InChIKey: PKUREZXQXDANPA-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 434.52, ALogP 3.55, HBA 6, HBD 1, PSA 89.4, QED 0.62
Compound (SMILES): CCC(CC)Cn1cc(C2(c3cccc(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cn1
InChIKey: YZUUNTCUAMHFQT-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 434.52, ALogP 3.55, HBA 6, HBD 1, PSA 89.4, QED 0.58
Compound (SMILES): CCCCn1cc(C2(c3cccc(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cn1
InChIKey: FSNVWNQXKNFHPF-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 406.47, ALogP 2.91, HBA 6, HBD 1, PSA 89.4, QED 0.64
Compound (SMILES): CN1C(=O)C(c2cccc(-c3cccnc3F)c2)(c2cnn(C3CCCC3)c2)N=C1N
InChIKey: APLGTNIWHISFNN-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 418.48, ALogP 3.23, HBA 6, HBD 1, PSA 89.4, QED 0.66
Compound (SMILES): CN1C(=O)C(c2ccsc2)(c2cccc(-c3cncnc3)c2)N=C1N
InChIKey: GCIHPVGAAJVLEF-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 349.42, ALogP 2.24, HBA 6, HBD 1, PSA 84.47, QED 0.79
Compound (SMILES): Cc1cc(C2(c3cccc(-c4cncnc4)c3)N=C(N)N(C)C2=O)cs1
InChIKey: UDYLXYFIJLPZAV-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 363.45, ALogP 2.54, HBA 6, HBD 1, PSA 84.47, QED 0.77
Compound (SMILES): Cc1sccc1C1(c2cccc(-c3cncnc3)c2)N=C(N)N(C)C1=O
InChIKey: AWSZXXRYNSNVQU-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 363.45, ALogP 2.54, HBA 6, HBD 1, PSA 84.47, QED 0.77
Compound (SMILES): CCc1cc(C2(c3cccc(-c4cncnc4)c3)N=C(N)N(C)C2=O)cs1
InChIKey: GAYCZOAOOLHOPO-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 377.47, ALogP 2.8, HBA 6, HBD 1, PSA 84.47, QED 0.76
Compound (SMILES): CCc1cc(C2(c3cccc(-c4cncnc4)c3)N=C(N)N(C)C2=O)c(C)s1
InChIKey: VLFTWHOZHAMTTE-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 391.5, ALogP 3.11, HBA 6, HBD 1, PSA 84.47, QED 0.74
Compound (SMILES): CN1C(=O)C(c2cccc(-c3cncnc3)c2)(c2csc(Cl)c2)N=C1N
InChIKey: ABAOMGTVATUZIR-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 383.86, ALogP 2.89, HBA 6, HBD 1, PSA 84.47, QED 0.75
Compound (SMILES): Cc1cc(C2(c3cccc(-c4cncnc4)c3)N=C(N)N(C)C2=O)c(Cl)s1
InChIKey: ZWXIWSLPGZVVNP-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 1150 nM (pChEMBL 5.940000057220459)
Descriptors: MW 397.89, ALogP 3.2, HBA 6, HBD 1, PSA 84.47, QED 0.74
Compound (SMILES): CCC(=O)c1cc(C2(c3cccc(-c4cncnc4)c3)N=C(N)N(C)C2=O)cs1
InChIKey: QKCQMQCRKHZUPK-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 405.48, ALogP 2.83, HBA 7, HBD 1, PSA 101.54, QED 0.66
Compound (SMILES): CN1C(=O)C(c2ccsc2)(c2cccc(-c3cccnc3)c2)N=C1N
InChIKey: AOGBXAFIKRFUPJ-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 by FRET assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 348.43, ALogP 2.84, HBA 5, HBD 1, PSA 71.58, QED 0.79
Compound (SMILES): CN1C(=O)C(c2ccsc2)(c2cccc(-c3cccnc3F)c2)N=C1N
InChIKey: VCKGJRZFNMIOEB-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 expressed in CHO cells expressing wild type human APP assessed as inhibition of amyloid beta-40 or 42 production by ELISA assay
Measurement: EC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 366.42, ALogP 2.98, HBA 5, HBD 1, PSA 71.58, QED 0.72