lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1N1CCc2nc(Nc3ccc(C(=O)N4CCN(C)CC4)nc3)ncc2C1
InChIKey: NNMZLFIDOZESFR-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 630.68, ALogP 5.15, HBA 8, HBD 2, PSA 106.59, QED 0.3
Compound (SMILES): Cc1ccc(NC(=O)c2cc(C(F)(F)F)ccn2)cc1N1CCc2nc(Nc3ccc(N4CCN(C)CC4)cc3)ncc2C1
InChIKey: PJPZHMVRKXWUJC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 602.67, ALogP 5.51, HBA 8, HBD 2, PSA 89.52, QED 0.3
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1N1CCc2nc(Nc3ccc(C(=O)NC4CCN(C)CC4)nc3)ncc2C1
InChIKey: QRCADIJQEQMSLL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 644.7, ALogP 5.58, HBA 8, HBD 3, PSA 115.38, QED 0.24
Compound (SMILES): Cc1ccc(NC(=O)CC(C)C(F)(F)F)cc1N1CCc2nc(Nc3ccc(OCCN4CCCC4)cc3)ncc2C1
InChIKey: CEINQDWSZHAZSK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 582.67, ALogP 6.09, HBA 7, HBD 2, PSA 82.62, QED 0.3
Compound (SMILES): Cc1ccc(NC(=O)CC(C)C(F)(F)F)cc1N1CCc2nc(Nc3ccc(OCCN4CCN(C)CC4)cc3)ncc2C1
InChIKey: UZICUOYVCKOCLZ-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 611.71, ALogP 5.24, HBA 8, HBD 2, PSA 85.86, QED 0.32
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(n3)CCN(c3cc(NC(=O)c5cccc(C(F)(F)F)c5)ccc3Cl)C4=O)cc2)CC1
InChIKey: SGLDXZLAQLSXFP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 636.08, ALogP 6.1, HBA 7, HBD 2, PSA 93.7, QED 0.26
Compound (SMILES): Cc1ccc(NC(=O)CCC(F)(F)F)cc1N1CCc2nc(Nc3ccc(C(=O)N4CCN(C)CC4)cc3)ncc2C1
InChIKey: NEKBJPNERWJTIC-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 581.64, ALogP 4.76, HBA 7, HBD 2, PSA 93.7, QED 0.42
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1N1CCc2nc(Nc3ccc(S(=O)(=O)NC4CC4)cc3)ncc2C1
InChIKey: SCDTVQOOFJOJPO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 622.67, ALogP 5.8, HBA 7, HBD 3, PSA 116.32, QED 0.23
Compound (SMILES): Cc1ccc(NC(=O)c2cc(C(F)(F)F)ccn2)cc1N1CCc2nc(Nc3ccc(N4CCN(C)CC4)cc3)ncc2C1=O
InChIKey: JCYJCYDKQAEPJA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 616.65, ALogP 5.15, HBA 8, HBD 2, PSA 106.59, QED 0.31
Compound (SMILES): Cc1ccc(NC(=O)c2cc(C(F)(F)F)ccn2)cc1N1CCc2nc(Nc3ccc(C(=O)N4CCN(C)CC4)cc3)ncc2C1
InChIKey: RPKWQQFQJOCDPR-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 630.68, ALogP 5.15, HBA 8, HBD 2, PSA 106.59, QED 0.3
Compound (SMILES): Cc1cc(Nc2ncc3c(n2)CCN(c2cc(NC(=O)c4cccc(C(F)(F)F)c4)ccc2Cl)C3=O)ccc1N1CCN(C)CC1
InChIKey: LCIAAEMZZHAWAG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 650.11, ALogP 6.41, HBA 7, HBD 2, PSA 93.7, QED 0.25
Compound (SMILES): CNC(=O)c1ccc(Nc2ncc3c(n2)CCN(c2cc(NC(=O)c4cccc(C(F)(F)F)c4)ccc2Cl)C3)cc1
InChIKey: KFKOANBFFZCCOA-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 581, ALogP 6.07, HBA 6, HBD 3, PSA 99.25, QED 0.26
Compound (SMILES): CNC(=O)c1ccc(Nc2ncc3c(n2)CCN(c2cc(NC(=O)c4cc(F)cc(C(F)(F)F)c4)ccc2Cl)C3)cc1
InChIKey: SBVIPGRXWKGSTR-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 598.99, ALogP 6.21, HBA 6, HBD 3, PSA 99.25, QED 0.23
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1N1CCc2nc(Nc3ccc(N4CCNCC4)cc3)ncc2C1=O
InChIKey: OULJVONSBCUARX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 601.63, ALogP 5.41, HBA 7, HBD 3, PSA 102.49, QED 0.27
Compound (SMILES): CNC(=O)c1ccc(Nc2ncc3c(n2)CCN(c2cc(NC(=O)c4cc(C(F)(F)F)ccn4)ccc2Cl)C3)cc1
InChIKey: FLJSOYXRJCMRAE-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 581.99, ALogP 5.46, HBA 7, HBD 3, PSA 112.14, QED 0.28
Compound (SMILES): CCCc1cnc(N2CC[C@@H](Oc3ccc([C@H](C)NC(C)=O)cc3)C2)nc1
InChIKey: ZDPYDAFWMQLOPF-MGPUTAFESA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00763
Assay: Spectrophotometric 384 Well Assay: Malonyl CoA formation by acetyl CoA carboxylases is stoichometrically linked to the consumption of ATP. ACC2 activity is measured in a NADH-linked kinetic method measuring ADP generated during the ACC reaction using a coupled lactate dehydrogenase/pyruvate kinase reaction.For biological testing, a human ACC2 construct which lacks the 128 amino acids at the N-terminus for increased solubility (nt 385-6966 in Genbank entry AJ575592) is cloned. The protein is then expressed in insect cells using a baculoviral expression system. Protein purification is performed by anion exchange.All compounds are dissolved in dimethyl sulfoxide (DMSO) to a concentration of 10 mM.Assay reactions are then carried out in 384-well plates, with hACC2 in an appropriate dilution and at final assay concentrations (f.c.) of 100 mM Tris (pH 7.5), 10 mM trisodium citrate, 25 mM KHCO3, 10 mM MgCl2, 0.5 mg/ml BSA, 3.75 mM reduced L-glutathione, 15 U/ml lactate dehydrogenase, 0.5 mM phosphoenolpyruvate.
Measurement: IC50 = 714 nM (pChEMBL 6.150000095367432)
Descriptors: MW 368.48, ALogP 3.28, HBA 5, HBD 1, PSA 67.35, QED 0.81
Compound (SMILES): C[C@]12CCC3C4CCC(=O)C=C4CCC3C1C1CC1[C@@]21CCC(=O)O1
InChIKey: KAVBXXNJZQGZIT-CFCWNOQOSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding Assay: The test was carried out as in 1, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.The results of the binding tests and the ratio of the competition factors CF(PR) and CR(MR) are shown in Table 1, which for comparison also shows receptor binding values of drospirenone as reference substance A.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 340.46, ALogP 4.06, HBA 3, HBD 0, PSA 43.37, QED 0.62
Compound (SMILES): CC1CC2=CC(=O)CCC2C2CC[C@@]3(C)C(C4CC4[C@@]34CCC(=O)O4)C12
InChIKey: BBPIYWKWDHEGML-GMYFBYKVSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding Assay: The test was carried out as in 1, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.The results of the binding tests and the ratio of the competition factors CF(PR) and CR(MR) are shown in Table 1, which for comparison also shows receptor binding values of drospirenone as reference substance A.
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 354.49, ALogP 4.31, HBA 3, HBD 0, PSA 43.37, QED 0.61
Compound (SMILES): CCC1CC2=CC(=O)CCC2C2CC[C@@]3(C)C(C4CC4[C@@]34CCC(=O)O4)C12
InChIKey: OCKLEWKOKFDMHP-WUHVDZIJSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding Assay: The test was carried out as in 1, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.The results of the binding tests and the ratio of the competition factors CF(PR) and CR(MR) are shown in Table 1, which for comparison also shows receptor binding values of drospirenone as reference substance A.
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 368.52, ALogP 4.7, HBA 3, HBD 0, PSA 43.37, QED 0.63
Compound (SMILES): C=CC1CC2=CC(=O)CCC2C2CC[C@@]3(C)C(C4CC4[C@@]34CCC(=O)O4)C12
InChIKey: FBRSRKWFLZVSLF-WUHVDZIJSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding Assay: The test was carried out as in 1, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.The results of the binding tests and the ratio of the competition factors CF(PR) and CR(MR) are shown in Table 1, which for comparison also shows receptor binding values of drospirenone as reference substance A.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 366.5, ALogP 4.47, HBA 3, HBD 0, PSA 43.37, QED 0.51
Compound (SMILES): C[C@]12CCC3C4CCC(=O)C=C4CC(C4CC4)C3C1C1CC1[C@@]21CCC(=O)O1
InChIKey: KZGODNLSXIAMIQ-WKKHHKSOSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding Assay: The test was carried out as in 1, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.The results of the binding tests and the ratio of the competition factors CF(PR) and CR(MR) are shown in Table 1, which for comparison also shows receptor binding values of drospirenone as reference substance A.
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 380.53, ALogP 4.7, HBA 3, HBD 0, PSA 43.37, QED 0.62
Compound (SMILES): C[C@]12CCC3C4CCC(=O)C=C4[C@H](CO)CC3C1C1CC1[C@@]21CCC(=O)O1
InChIKey: CGXAYJDPWPSYLD-GYCQOJBWSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding Assay: The test was carried out as in 1, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.The results of the binding tests and the ratio of the competition factors CF(PR) and CR(MR) are shown in Table 1, which for comparison also shows receptor binding values of drospirenone as reference substance A.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 370.49, ALogP 3.28, HBA 4, HBD 1, PSA 63.6, QED 0.72
Compound (SMILES): C[C@]12CCC3C4CCC(=O)C=C4C4(CC4)CC3C1C1CC1[C@@]21CCC(=O)O1
InChIKey: NEYLJRNOSBUARA-DUAPPZKWSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding Assay: The test was carried out as in 1, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.The results of the binding tests and the ratio of the competition factors CF(PR) and CR(MR) are shown in Table 1, which for comparison also shows receptor binding values of drospirenone as reference substance A.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 366.5, ALogP 4.45, HBA 3, HBD 0, PSA 43.37, QED 0.59
Compound (SMILES): C[C@]12CCC3C4CCC(=O)C=C4C4CC4C3C1C1CC1[C@@]21CCC(=O)O1
InChIKey: WAORTEATHIIKSN-COBLQOHFSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding Assay: The test was carried out as in 1, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.The results of the binding tests and the ratio of the competition factors CF(PR) and CR(MR) are shown in Table 1, which for comparison also shows receptor binding values of drospirenone as reference substance A.
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 352.47, ALogP 3.92, HBA 3, HBD 0, PSA 43.37, QED 0.62
Compound (SMILES): COc1cccc(F)c1CN1C[C@H](NC(=O)c2ccc3[nH]nc(-c4ccnc(C)c4)c3c2)CC[C@H]1C(=O)N1CC(O[Si](C)(C)C(C)(C)C)CO1
InChIKey: MNMHDWDMZWIGLI-SURJGROGSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP Assay : Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 144.1 nM (pChEMBL 6.840000152587891)
Descriptors: MW 702.9
Compound (SMILES): CC(c1cc(C(=O)N2CCC(O)CC2)cc2c(=O)cc(N3CCOCC3)oc12)N(C)c1cc(F)cc(F)c1
InChIKey: UOZWDNWNBWHNIU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Enzyme Inhibition Assay: The inhibition of PI3Kβ, PI3Kα, PI3Kγ and PI3Kδ was evaluated in a Kinase Glo based enzyme activity assay using human recombinant enzymes. The assay measures depletion of ATP after incubation with enzyme, PIP2 and ATP plus compound. ATP at the end of the reaction is detected by addition of Kinase Glo reagent, in this the Ultra Glo luciferase (Promega) uses the ATP as a substrate to catalyze the mono-oxygenation of luciferin and the generation of light. A direct relationship exists between the luminescence measured with the Kinase-Glo Plus Reagent and the amount of ATP remaining in a completed kinase reaction and luminescence is inversely related to kinase activity.
Measurement: IC50 = 4315 nM (pChEMBL 5.369999885559082)
Descriptors: MW 527.57, ALogP 3.7, HBA 7, HBD 1, PSA 86.46, QED 0.54
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of recombinant human full-length N-terminal His-tagged CDK6/cyclinD3 expressed in baculovirus infected Sf9 insect cells using histone H1 as substrate measured after 60 mins by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): OCCOc1cc(CC2CCN(CCc3ccc4c(c3)C(O)CCO4)CC2)ccc1Br
InChIKey: HZCQCGLFELVCGS-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: Procedure:  1. A 10 mM solution of a test drug in DMSO was serially diluted with DMSO at four 5-fold dilutions to prepare 10, 2, 0.4 and 0.08 mM DMSO solutions.  2. Each test drug solution of step 1 or DMSO was diluted 160-fold with the human liver microsome solution and dispensed at a concentration of 80 uL/well to a microplate.  3. 10 uL of the substrate solution and 10 uL of the beta-NADPH solution were added to each well of step 2, and the mixture was incubated at 37C. for 10 min.  4. The reaction was terminated by the addition of 300 uL of methanol.  5. The reaction mixture was filtered and analyzed by LC-MS/MS.  3-4 Quantification and CalculationThe amount of 1'-hydroxybufuralol formed was determined by LC-MS/MS, and this value was used as the metabolic activity value of CYP2D6 in each well. The residual activity of each sample-supplemented group was determined by comparison with the activity in the well containing DMSO used as a test drug.
Measurement: IC50 = 40700 nM (pChEMBL 4.389999866485596)
Descriptors: MW 490.44, ALogP 4.13, HBA 5, HBD 2, PSA 62.16, QED 0.58
Compound (SMILES): O=C1c2cc(CCN3CCC(Cc4ccc(Br)c(OCCO)c4)CC3)ccc2OCC1O
InChIKey: ACJLTODAAAIJTN-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: Procedure:  1. A 10 mM solution of a test drug in DMSO was serially diluted with DMSO at four 5-fold dilutions to prepare 10, 2, 0.4 and 0.08 mM DMSO solutions.  2. Each test drug solution of step 1 or DMSO was diluted 160-fold with the human liver microsome solution and dispensed at a concentration of 80 uL/well to a microplate.  3. 10 uL of the substrate solution and 10 uL of the beta-NADPH solution were added to each well of step 2, and the mixture was incubated at 37C. for 10 min.  4. The reaction was terminated by the addition of 300 uL of methanol.  5. The reaction mixture was filtered and analyzed by LC-MS/MS.  3-4 Quantification and CalculationThe amount of 1'-hydroxybufuralol formed was determined by LC-MS/MS, and this value was used as the metabolic activity value of CYP2D6 in each well. The residual activity of each sample-supplemented group was determined by comparison with the activity in the well containing DMSO used as a test drug.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 504.42, ALogP 3.25, HBA 6, HBD 2, PSA 79.23, QED 0.58
Compound (SMILES): O=C1c2cc(CCN3CCC(Cc4ccc(Br)c(O)c4)CC3)ccc2OCC1O
InChIKey: CDQNHZRQGKLBDW-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: Procedure:  1. A 10 mM solution of a test drug in DMSO was serially diluted with DMSO at four 5-fold dilutions to prepare 10, 2, 0.4 and 0.08 mM DMSO solutions.  2. Each test drug solution of step 1 or DMSO was diluted 160-fold with the human liver microsome solution and dispensed at a concentration of 80 uL/well to a microplate.  3. 10 uL of the substrate solution and 10 uL of the beta-NADPH solution were added to each well of step 2, and the mixture was incubated at 37C. for 10 min.  4. The reaction was terminated by the addition of 300 uL of methanol.  5. The reaction mixture was filtered and analyzed by LC-MS/MS.  3-4 Quantification and CalculationThe amount of 1'-hydroxybufuralol formed was determined by LC-MS/MS, and this value was used as the metabolic activity value of CYP2D6 in each well. The residual activity of each sample-supplemented group was determined by comparison with the activity in the well containing DMSO used as a test drug.
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 460.37, ALogP 3.59, HBA 5, HBD 2, PSA 70, QED 0.71
Compound (SMILES): O=C1CCOc2ccc(CCN3CCC(Cc4ccc(Br)c(O)c4)CC3)cc21
InChIKey: QLWVACLCPWJPFS-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: Procedure:  1. A 10 mM solution of a test drug in DMSO was serially diluted with DMSO at four 5-fold dilutions to prepare 10, 2, 0.4 and 0.08 mM DMSO solutions.  2. Each test drug solution of step 1 or DMSO was diluted 160-fold with the human liver microsome solution and dispensed at a concentration of 80 uL/well to a microplate.  3. 10 uL of the substrate solution and 10 uL of the beta-NADPH solution were added to each well of step 2, and the mixture was incubated at 37C. for 10 min.  4. The reaction was terminated by the addition of 300 uL of methanol.  5. The reaction mixture was filtered and analyzed by LC-MS/MS.  3-4 Quantification and CalculationThe amount of 1'-hydroxybufuralol formed was determined by LC-MS/MS, and this value was used as the metabolic activity value of CYP2D6 in each well. The residual activity of each sample-supplemented group was determined by comparison with the activity in the well containing DMSO used as a test drug.
Measurement: IC50 = 9900 nM (pChEMBL 5)
Descriptors: MW 444.37, ALogP 4.62, HBA 4, HBD 1, PSA 49.77, QED 0.73
Compound (SMILES): O=c1ccoc2ccc(CCN3CCC(Cc4ccc(Br)c(O)c4)CC3)cc12
InChIKey: DOWPQDSKPOAVOT-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: Procedure:  1. A 10 mM solution of a test drug in DMSO was serially diluted with DMSO at four 5-fold dilutions to prepare 10, 2, 0.4 and 0.08 mM DMSO solutions.  2. Each test drug solution of step 1 or DMSO was diluted 160-fold with the human liver microsome solution and dispensed at a concentration of 80 uL/well to a microplate.  3. 10 uL of the substrate solution and 10 uL of the beta-NADPH solution were added to each well of step 2, and the mixture was incubated at 37C. for 10 min.  4. The reaction was terminated by the addition of 300 uL of methanol.  5. The reaction mixture was filtered and analyzed by LC-MS/MS.  3-4 Quantification and CalculationThe amount of 1'-hydroxybufuralol formed was determined by LC-MS/MS, and this value was used as the metabolic activity value of CYP2D6 in each well. The residual activity of each sample-supplemented group was determined by comparison with the activity in the well containing DMSO used as a test drug.
Measurement: IC50 = 16800 nM (pChEMBL 4.78000020980835)
Descriptors: MW 442.35, ALogP 4.76, HBA 4, HBD 1, PSA 53.68, QED 0.62
Compound (SMILES): COCCOc1cc(CC2CCN(CCc3ccc4c(c3)C(=O)CC(O)O4)CC2)ccc1Br
InChIKey: QVPKMBDEMNWGPO-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: Procedure:  1. A 10 mM solution of a test drug in DMSO was serially diluted with DMSO at four 5-fold dilutions to prepare 10, 2, 0.4 and 0.08 mM DMSO solutions.  2. Each test drug solution of step 1 or DMSO was diluted 160-fold with the human liver microsome solution and dispensed at a concentration of 80 uL/well to a microplate.  3. 10 uL of the substrate solution and 10 uL of the beta-NADPH solution were added to each well of step 2, and the mixture was incubated at 37C. for 10 min.  4. The reaction was terminated by the addition of 300 uL of methanol.  5. The reaction mixture was filtered and analyzed by LC-MS/MS.  3-4 Quantification and CalculationThe amount of 1'-hydroxybufuralol formed was determined by LC-MS/MS, and this value was used as the metabolic activity value of CYP2D6 in each well. The residual activity of each sample-supplemented group was determined by comparison with the activity in the well containing DMSO used as a test drug.
Measurement: IC50 = 44900 nM (pChEMBL 4.349999904632568)
Descriptors: MW 518.45, ALogP 4.26, HBA 6, HBD 1, PSA 68.23, QED 0.5
Compound (SMILES): COCCOc1cc(CC2CCN(CCc3ccc4occ(O)c(=O)c4c3)CC2)ccc1Br
InChIKey: RYTARPUUWKIZPO-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: Procedure:  1. A 10 mM solution of a test drug in DMSO was serially diluted with DMSO at four 5-fold dilutions to prepare 10, 2, 0.4 and 0.08 mM DMSO solutions.  2. Each test drug solution of step 1 or DMSO was diluted 160-fold with the human liver microsome solution and dispensed at a concentration of 80 uL/well to a microplate.  3. 10 uL of the substrate solution and 10 uL of the beta-NADPH solution were added to each well of step 2, and the mixture was incubated at 37C. for 10 min.  4. The reaction was terminated by the addition of 300 uL of methanol.  5. The reaction mixture was filtered and analyzed by LC-MS/MS.  3-4 Quantification and CalculationThe amount of 1'-hydroxybufuralol formed was determined by LC-MS/MS, and this value was used as the metabolic activity value of CYP2D6 in each well. The residual activity of each sample-supplemented group was determined by comparison with the activity in the well containing DMSO used as a test drug.
Measurement: IC50 = 37600 nM (pChEMBL 4.420000076293945)
Descriptors: MW 516.43, ALogP 4.78, HBA 6, HBD 1, PSA 72.14, QED 0.41
Compound (SMILES): Oc1cc(CC2CCN(CCc3ccc4c(c3)C(O)CCO4)CC2)ccc1Br
InChIKey: WWMCHEJDFWDIKR-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: Procedure:  1. A 10 mM solution of a test drug in DMSO was serially diluted with DMSO at four 5-fold dilutions to prepare 10, 2, 0.4 and 0.08 mM DMSO solutions.  2. Each test drug solution of step 1 or DMSO was diluted 160-fold with the human liver microsome solution and dispensed at a concentration of 80 uL/well to a microplate.  3. 10 uL of the substrate solution and 10 uL of the beta-NADPH solution were added to each well of step 2, and the mixture was incubated at 37C. for 10 min.  4. The reaction was terminated by the addition of 300 uL of methanol.  5. The reaction mixture was filtered and analyzed by LC-MS/MS.  3-4 Quantification and CalculationThe amount of 1'-hydroxybufuralol formed was determined by LC-MS/MS, and this value was used as the metabolic activity value of CYP2D6 in each well. The residual activity of each sample-supplemented group was determined by comparison with the activity in the well containing DMSO used as a test drug.
Measurement: IC50 = 40300 nM (pChEMBL 4.389999866485596)
Descriptors: MW 446.39, ALogP 4.47, HBA 4, HBD 2, PSA 52.93, QED 0.71
Compound (SMILES): COc1ncc(-c2nc3c(n2C(C)C)C(c2ccc(Cl)cc2)N(c2cc(Cl)cn(C)c2=O)C3=O)c(OC)n1
InChIKey: AGBSXNCBIWWLHD-UHFFFAOYSA-N
Target: Protein Mdm4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15151
Assay: Binding affinity to human MDM4 assessed as inhibition constant
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 555.42, ALogP 4.69, HBA 9, HBD 0, PSA 104.37, QED 0.34
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2cccc3c2C(=O)CC3)n1
InChIKey: QUSSZSMDFABHLI-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of human PTK2 (411-689 residues) expressed in Hi-5 cells
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 555.56, ALogP 4.99, HBA 8, HBD 2, PSA 105.68, QED 0.42
Compound (SMILES): CCc1cc(C#N)cc(-c2ccc3c(c2)C2(N=C(C)C(N)=N2)[C@]2(CC[C@H](OC)CC2)C3)c1
InChIKey: MZMGBLWHPUKZKF-HAOYJSTOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Diluted TR-FRET Assay: TR-FRET AssayThe beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes.
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 426.56, ALogP 4.9, HBA 5, HBD 1, PSA 83.76, QED 0.76
Compound (SMILES): COCc1cc(C#N)cc(-c2ccc3c(c2)C2(N=C(C)C(N)=N2)[C@]2(CC[C@H](OC)CC2)C3)c1
InChIKey: WXWZQOAPXMLOGN-HAOYJSTOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Diluted TR-FRET Assay: TR-FRET AssayThe beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes.
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 442.56, ALogP 4.49, HBA 6, HBD 1, PSA 92.99, QED 0.76
Compound (SMILES): CC1=NC2(N=C1N)c1cc(-c3cncc(C(F)(F)F)c3)ccc1C[C@]21CC[C@@H](OC(F)F)CC1
InChIKey: VABJLQOQMZEOHJ-VYNBAUGJSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 478.46, ALogP 5.48, HBA 5, HBD 1, PSA 72.86, QED 0.59
Compound (SMILES): CC1=NC2(N=C1N)c1cc(-c3cc(Cl)cc(C#N)c3)ccc1C[C@]21CC[C@@H](OC(F)F)CC1
InChIKey: XHPVFJGGOWNHQR-QXONTCKQSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Diluted TR-FRET Assay: TR-FRET AssayThe beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 468.94, ALogP 5.59, HBA 5, HBD 1, PSA 83.76, QED 0.64
Compound (SMILES): CC1=NC2(N=C1N)c1cc(-c3cc(F)cc(F)c3)ccc1C[C@]21CC[C@@H](OC(F)F)CC1
InChIKey: KGNLPACQRCXMGM-AHLJTMJASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 445.46, ALogP 5.34, HBA 4, HBD 1, PSA 59.97, QED 0.65
Compound (SMILES): COc1cc(-c2ccc3c(c2)C2(N=C(C)C(N)=N2)[C@]2(CC[C@H](OC(F)F)CC2)C3)cc(C#N)c1F
InChIKey: GBNJNJPEBSZUOQ-GKDSVWLLSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 482.51, ALogP 5.08, HBA 6, HBD 1, PSA 92.99, QED 0.66
Compound (SMILES): CC1=NC2(N=C1N)c1cc(Br)ccc1CC21CCC(C(F)(F)F)CC1
InChIKey: NTHHXIKGFGHHJO-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 19300 nM (pChEMBL 4.710000038146973)
Descriptors: MW 414.27, ALogP 4.73, HBA 3, HBD 1, PSA 50.74, QED 0.66
Compound (SMILES): COCc1cc(-c2ccc3c(c2)C2(N=C(C)C(N)=N2)[C@]2(CC[C@H](OC)CC2)C3)cc(C#N)c1F
InChIKey: XWRREAIVFZDEEK-JZGZJDTKSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 460.55, ALogP 4.63, HBA 6, HBD 1, PSA 92.99, QED 0.72
Compound (SMILES): CC1=NC2(N=C1N)c1cc(-c3cncc(Cl)c3)ccc1CC21CCC(C(F)F)CC1
InChIKey: YGKQMZYHQKDGRZ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 748 nM (pChEMBL 6.130000114440918)
Descriptors: MW 428.91, ALogP 5.38, HBA 4, HBD 1, PSA 63.63, QED 0.7
Compound (SMILES): CC1=NC2(CCOc3ccc(-c4cccc(F)c4F)cc32)N=C1N
InChIKey: NMPGDLCHDFBBBC-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: FRET Assay: The enzyme (truncated form) was diluted to 6 μg/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 μM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 μl) was added to the plate then 1 μl of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 μl) was then added, mixed and the reaction proceeded for 15 minutes at r.t. The reaction was stopped with the addition of Stop solution (7 μl, NaAcetate, pH 9). The fluorescence of the product was measured on a Victor II plate reader with an excitation wavelength of 340 nm and an emission wavelength of 615 nm. The assay was performed in a Costar 384 well round bottom, low volume, non-binding surface plate (Corning #3676). The final concentration of the enzyme was 2.7 μg/ml; the final concentration of substrate was 100 nM (Km of 250 nM). The dimethylsulphoxide control, instead of test compound, defined the 100% activity level and 0% activity was defined by wells lacking enzyme (replaced with reaction buffer). A control inhibitor was also used in dose response assays and had an 1050 of 150 nM.
Measurement: IC50 = 6710 nM (pChEMBL 5.170000076293945)
Descriptors: MW 327.33, ALogP 3.4, HBA 4, HBD 1, PSA 59.97, QED 0.87
Compound (SMILES): COc1cccc(-c2ccc3c(c2)C2(CCO3)N=C(C)C(N)=N2)c1F
InChIKey: HZUBJQJZQJTUIS-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: TR-FRET Assay: The β-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human β-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc 10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in −80° C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 μg/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 μM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 μl) was added to the plate then 1 μl of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 μl) was then added, mixed and the reaction proceeded for 15 minutes at r.t. The reaction was stopped with the addition of Stop solution (7 μl, NaAcetate, pH 9). The fluorescence of the product was measured on a Victor II plate reader with an excitation wavelength of 340 nm and an emission wavelength of 615 nm. The assay was performed in a Costar 384 well round bottom, low volume, non-binding surface plate (Corning #3676). The final concentration of the enzyme was 2.7 g/ml; the final concentration of substrate was 100 nM (Km of 250 nM). The dimethylsulphoxide control, instead of test compound, defined the 100% activity level and 0% activity was defined by wells lacking enzyme (replaced with reaction buffer). A control inhibitor was also used in dose response assays and had an IC50 of 150 nM.
Measurement: IC50 = 6850 nM (pChEMBL 5.159999847412109)
Descriptors: MW 339.37, ALogP 3.27, HBA 5, HBD 1, PSA 69.2, QED 0.91
Compound (SMILES): COc1cc(F)c(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: CZRMENLRCXEIFA-GSBZAIBZSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin)
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 741.58, ALogP 10.63, HBA 4, HBD 1, PSA 76.07, QED 0.2
Compound (SMILES): COc1ncc(-c2ccc(C(=O)O)cc2C)cc1-c1ncc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: SVVFIIYREHMBTN-UNCTUWKVSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 725.56, ALogP 9.28, HBA 6, HBD 1, PSA 101.85, QED 0.2