lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)CNC(=O)c1nc(-c2cccc3ncccc23)ccc1O
InChIKey: DIURAOCBPHFCPT-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of human KDM4C preincubated for 15 mins followed by substrate addition and measured after 15 mins using H3(1-21)K9Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 323.31, ALogP 1.82, HBA 5, HBD 3, PSA 112.41, QED 0.67
Compound (SMILES): O=C(O)CNC(=O)c1nc(Nc2ccc([N+](=O)[O-])cn2)ccc1O
InChIKey: AUTPWJQNUXXRBG-UHFFFAOYSA-N
Target: Lysine-specific demethylase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4C1
Assay: Inhibition of human KDM3A preincubated for 15 mins followed by substrate addition and measured after 5 mins using H3(1-21)K9Me2-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 41900 nM (pChEMBL 4.380000114440918)
Descriptors: MW 333.26, ALogP 0.65, HBA 8, HBD 4, PSA 167.58, QED 0.44
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2ccc3ccncc3c2)[nH]1
InChIKey: LFKMEUIGEGSJAQ-SXOMAYOGSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 515.7, ALogP 5.83, HBA 5, HBD 2, PSA 90.98, QED 0.3
Compound (SMILES): Nc1ncnc2c1c(-c1cc3cc(O)ccc3[nH]1)nn2C1CCOCC1
InChIKey: BSAIWOVMAFXWGG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition Assay: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110Î´/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 ug/ml). Reactions are initiated by the addition of ATP containing 10 uCi of γ-32P-ATP to a final concentration 10 or 100 uM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 ul 1N HCl followed by 160 ul CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen (Storm, Amersham), and quantitated. For each compound, kinase activity is measured at 10-12 inhibitor concentrations representing two-fold dilutions from the highest concentration tested (typically, 200 uM).
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 350.38, ALogP 2.61, HBA 7, HBD 3, PSA 114.87, QED 0.51
Compound (SMILES): Nc1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)nc1
InChIKey: VHRHISVDVXQRMH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of human KDM5B preincubated for 15 mins followed by substrate addition and measured after 20 mins using H3(1-21)K4Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 39800 nM (pChEMBL 4.400000095367432)
Descriptors: MW 303.28, ALogP 0.32, HBA 7, HBD 5, PSA 150.46, QED 0.53
Compound (SMILES): CC(=O)N1CCC(n2nc(-c3cc4cc(O)cc(Cl)c4[nH]3)c3c(N)ncnc32)CC1
InChIKey: FDJSQHVHCVOQLN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PI3Kalpha preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 425.88, ALogP 3.1, HBA 7, HBD 3, PSA 125.95, QED 0.45
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccc(C)nc3cc2F)[nH]1
InChIKey: ANZQYGJNTXEGBA-RSXGOPAZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 533.69, ALogP 5.89, HBA 5, HBD 2, PSA 90.98, QED 0.3
Compound (SMILES): CN(C)C(=O)c1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)cc1
InChIKey: ZBMILIUDWNGSSH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4C1
Assay: Inhibition of human KDM3A preincubated for 15 mins followed by substrate addition and measured after 5 mins using H3(1-21)K9Me2-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 358.35, ALogP 1.05, HBA 6, HBD 4, PSA 131.86, QED 0.61
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccc(C)nc3cc2CC)[nH]1
InChIKey: MZCMRPRNHRPNAJ-IZLXSDGUSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 543.76, ALogP 6.31, HBA 5, HBD 2, PSA 90.98, QED 0.26
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccc(C)nc3cc2OC)o1
InChIKey: VMWGQRJJRHORGQ-FTJBHMTQSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 34000 nM (pChEMBL 4.46999979019165)
Descriptors: MW 546.71, ALogP 6.03, HBA 7, HBD 1, PSA 97.56, QED 0.28
Compound (SMILES): C[C@@H](Oc1cc(NC(=O)c2cn(CCN3CCOCC3)c3cc(Br)c(C=O)nc23)ncc1C#N)c1c(Cl)cncc1Cl
InChIKey: CGZXQBNAWSMHFF-MRXNPFEDSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam and testosterone as substrate in presence NADPH regenerating system
Measurement: IC50 = 2710 nM (pChEMBL 5.570000171661377)
Descriptors: MW 673.36, ALogP 5.3, HBA 10, HBD 1, PSA 135.26, QED 0.23
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccc(C)nc3cc2F)o1
InChIKey: OTDRPXYPNVACGD-RSXGOPAZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 534.68, ALogP 6.16, HBA 6, HBD 1, PSA 88.33, QED 0.3
Compound (SMILES): Nc1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)cc1
InChIKey: JCSJQUCGCIEKPQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4C1
Assay: Inhibition of human KDM3A preincubated for 15 mins followed by substrate addition and measured after 5 mins using H3(1-21)K9Me2-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 52000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 302.29, ALogP 0.93, HBA 6, HBD 5, PSA 137.57, QED 0.52
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(N)(CCC3CC3)c3ccncc3)ccc2F)c1
InChIKey: AGVFYPDLNPHKER-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as substrate measured after 5 mins by microplate reader analysis
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 552.58, ALogP 5.53, HBA 6, HBD 3, PSA 111.85, QED 0.24
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3ccc(=O)n(C)c3cc2OC)o1
InChIKey: UWIASJNPIIGSRX-FTJBHMTQSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 576.74, ALogP 5.41, HBA 8, HBD 1, PSA 106.67, QED 0.27
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3nccnc3cc2OC)[nH]1
InChIKey: MDGXAKPJTXGCJJ-RPWUZVMVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 546.72, ALogP 5.24, HBA 7, HBD 2, PSA 113.1, QED 0.28
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccc3nc(N4CCCC4)ccc3c2)[nH]1
InChIKey: BPGNCVTVTQPXKS-PXJZQJOASA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 570.78, ALogP 6.04, HBA 6, HBD 2, PSA 94.22, QED 0.26
Compound (SMILES): COc1cc2c(cc1OC)[C@@H](C)C(=O)N(C)C=C2
InChIKey: DIOZLEANHAFFJH-SECBINFHSA-N
Target: C-C motif chemokine 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P13500
Assay: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 247.29, ALogP 2.25, HBA 3, HBD 0, PSA 38.77, QED 0.8
Compound (SMILES): COc1cccc(N2CCN(Cc3nc(N)nc(Nc4ccc(C)c(C)c4)n3)CC2)c1
InChIKey: STKSULQULJWEMU-UHFFFAOYSA-N
Target: NADPH oxidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPH5
Assay: Nox4 Assay: Cells: HEK (CJ Nox4) stably expressing Nox4 was purchased from Redoxis AB (Lund). The adherent cells were cultivated in RPMI 1640 with L-Glutamine were supplemented with FBS (10%), penicillin (10 U/ml) streptomycin (100 μg/ml) and neomycin (200 μg/ml) at 37° C. in air with 5% CO2.Hydrogen peroxide produced by Nox4 was measured (fluorescence emission: 590 and excitation: 544) using Amplex red (Molecular Probes) in Fluorescan Ascent plate reader Type 374. Cells were collected from cultures by Trypsin mediated detachment of adherent cells. Cells were seeded in 96-well plates at a density of 50 000 cells in 200 l assay volume. Inhibitors were added for 30 min (37° C.) and then reagents was added to give a final concentration of Amplex Red 35 mM and 0.17 U/ml horseradish peroxidase. Nox4 activity was measured up to 100 min with readings every minute. Inhibition curves of different Nox4 inhibitors were evaluated at 50% inhibition (IC50) in comparison to cell control without inhibitor present. Y-axes: turnover of hydrogen peroxide; x-axes: concentration of inhibitor. Inhibitors were diluted in a compound plate in DMSO (100%) then transferred to Hanks buffer solution and in assay plate DMSO were 2% in all the wells.Compounds (Nox inhibitors) were diluted at 3× working concentration and titrated from 200 μM to 0.003 μM in 11 steps.
Measurement: IC50 = 1680 nM (pChEMBL 5.78000020980835)
Descriptors: MW 419.53, ALogP 3.15, HBA 8, HBD 2, PSA 92.43, QED 0.63
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3cccnc3nc2OC)o1
InChIKey: SPRMKKWNBGDRLB-RPBOFIJWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 547.7, ALogP 5.5, HBA 8, HBD 1, PSA 110.45, QED 0.28
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccc3nc(-n4cccn4)ccc3c2)[nH]1
InChIKey: LGSKPPYSKWOZRH-IAPPQJPRSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 567.74, ALogP 5.63, HBA 7, HBD 2, PSA 108.8, QED 0.21
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(C2=CC3SC=NC3C=C2)[nH]1
InChIKey: DAYIQZXDBBYZNJ-HNMULJTMSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 509.72, ALogP 4.69, HBA 6, HBD 2, PSA 90.45, QED 0.42
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccccc3[nH]c2=O)[nH]1
InChIKey: SVRMBDNTAIBTAK-NOZRDPDXSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 517.67, ALogP 4.74, HBA 5, HBD 3, PSA 110.95, QED 0.32
Compound (SMILES): COc1cccc2cc(-c3nn(C4CCOCC4)c4ncnc(N)c34)[nH]c12
InChIKey: ZEKMMWTXUQTYFE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 364.41, ALogP 2.92, HBA 7, HBD 2, PSA 103.87, QED 0.58
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3ccc(C)nc3cc2OC)[nH]1
InChIKey: BBRYNDYUWCVFAV-SXOMAYOGSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
Descriptors: MW 559.76, ALogP 6.15, HBA 6, HBD 2, PSA 100.21, QED 0.24
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3ccc(=O)n(C)c3cc2OC)[nH]1
InChIKey: LPSGBWOQABTCDV-FTJBHMTQSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 575.75, ALogP 5.15, HBA 7, HBD 2, PSA 109.32, QED 0.27
Compound (SMILES): CC(C)n1nc(-c2cc3cccc(O)c3[nH]2)c2c(N)ncnc21
InChIKey: DWMSSWRQJCJQFL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of human PI3Kbeta preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 308.35, ALogP 2.84, HBA 6, HBD 3, PSA 105.64, QED 0.53
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(C2=CC3OC=NC3C=C2)[nH]1
InChIKey: PTTHXWHSGFRYLP-HNMULJTMSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 58000 nM (pChEMBL 4.239999771118164)
Descriptors: MW 493.65, ALogP 3.98, HBA 6, HBD 2, PSA 99.68, QED 0.45
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3cn(C)nc3cc2OC)[nH]1
InChIKey: LVBJLNXVNGDXNM-RPBOFIJWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 548.73, ALogP 5.18, HBA 7, HBD 2, PSA 105.14, QED 0.29
Compound (SMILES): O=C(O)CNC(=O)c1nc(-c2ccccc2-c2ccccc2)ccc1O
InChIKey: CWMDDHZCTORRMW-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of human KDM5B preincubated for 15 mins followed by substrate addition and measured after 20 mins using H3(1-21)K4Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 88800 nM (pChEMBL 4.050000190734863)
Descriptors: MW 348.36, ALogP 2.94, HBA 4, HBD 3, PSA 99.52, QED 0.66
Compound (SMILES): Cc1c(Br)cc(NC(=O)CS(=O)(=O)O)cc1Br
InChIKey: PGYFUNHIFMBZCB-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 387.05, ALogP 2.35, HBA 3, HBD 2, PSA 83.47, QED 0.78
Compound (SMILES): COc1cccc2ccc(-c3cc(-c4ccc5cccc(OC)c5c4O)c4cccc(OC)c4c3O)c(O)c12
InChIKey: QNSPJOAEPRYOBU-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Agonist activity at RXRalpha-LBD (unknown origin) assessed as transactivation by measuring increase in fluorescein-labelled coactivator PGC-1alpha peptide recruitment by Lanthascreen TR-FRET
Measurement: EC50 = 52900 nM (pChEMBL 4.28000020980835)
Descriptors: MW 518.57, ALogP 7.62, HBA 6, HBD 3, PSA 88.38, QED 0.22
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(O)(CCC3CC3)c3ccccn3)ccc2F)c1
InChIKey: XXMBQXWQIGCREG-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as substrate measured after 5 mins by microplate reader analysis
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 553.56, ALogP 5.56, HBA 6, HBD 3, PSA 106.06, QED 0.24
Compound (SMILES): CC(C)n1nc(-c2cc3cc(O)cc(F)c3[nH]2)c2c(N)ncnc21
InChIKey: LUKIMGGLSGHDAN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human PI3Kgamma preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 326.34, ALogP 2.98, HBA 6, HBD 3, PSA 105.64, QED 0.52
Compound (SMILES): Nc1ncnc2c1c(-c1cc3cccc(O)c3[nH]1)nn2C1CCOCC1
InChIKey: FPBHABZEDHGIJO-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 350.38, ALogP 2.61, HBA 7, HBD 3, PSA 114.87, QED 0.51
Compound (SMILES): CN[C@@H]1COc2c(S(=O)(=O)NC(=O)Nc3c4c(cc5c3CCC5)CCC4)cnn2C1
InChIKey: NDRARVKETDZHBS-AWEZNQCLSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in LPS-stimulated human monocyte-derived macrophage assessed as reduction in ILbeta secretion in presence of ATP
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 431.52, ALogP 1.35, HBA 7, HBD 3, PSA 114.35, QED 0.67
Compound (SMILES): O=C(O)CNC(=O)c1nc(Nc2ccc([N+](=O)[O-])cc2)ccc1O
InChIKey: ITMKUXMZMOBJES-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of human KDM4C preincubated for 15 mins followed by substrate addition and measured after 15 mins using H3(1-21)K9Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 332.27, ALogP 1.25, HBA 7, HBD 4, PSA 154.69, QED 0.45
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H]2NC(=O)[C@H](NC(=O)CN)CSSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(=O)O)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)c(I)c1)C(=O)N[C@@H](CCCN)C(=O)N[C@H](C(=O)N[C@H](CC(=O)N[C@@H](CCCNC(=N)N)C(=O)O)Cc1ccc(O)cc1)CSSC2(C)C
InChIKey: PREQDDPQCXZODC-TZHKBYJCSA-N
Target: Neuronal acetylcholine receptor; alpha2/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12392
Assay: Inhibition of rat alpha2beta4 nAChR expressed in xenopus oocytes assessed as inhibition of Ach- induced response at -70 mV holding potential and measured for 1 to 5 days in presence of Ach stimulation by voltage-clamp based electrophysiological method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1873.97
Compound (SMILES): O=C(O)CNC(=O)c1nc(-c2cccc3ncccc23)ccc1O
InChIKey: DIURAOCBPHFCPT-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of human KDM5B preincubated for 15 mins followed by substrate addition and measured after 20 mins using H3(1-21)K4Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 40500 nM (pChEMBL 4.389999866485596)
Descriptors: MW 323.31, ALogP 1.82, HBA 5, HBD 3, PSA 112.41, QED 0.67
Compound (SMILES): O=C(O)CNC(=O)c1nc(Nc2ccc([N+](=O)[O-])cn2)ccc1O
InChIKey: AUTPWJQNUXXRBG-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of human KDM4C preincubated for 15 mins followed by substrate addition and measured after 15 mins using H3(1-21)K9Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 44400 nM (pChEMBL 4.349999904632568)
Descriptors: MW 333.26, ALogP 0.65, HBA 8, HBD 4, PSA 167.58, QED 0.44
Compound (SMILES): Nc1ncnc2c1c(-c1cc3cc(O)ccc3[nH]1)nn2C1CCOCC1
InChIKey: BSAIWOVMAFXWGG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00750
Assay: Inhibition Assay: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110Î´/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 ug/ml). Reactions are initiated by the addition of ATP containing 10 uCi of γ-32P-ATP to a final concentration 10 or 100 uM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 ul 1N HCl followed by 160 ul CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen (Storm, Amersham), and quantitated. For each compound, kinase activity is measured at 10-12 inhibitor concentrations representing two-fold dilutions from the highest concentration tested (typically, 200 uM).
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 350.38, ALogP 2.61, HBA 7, HBD 3, PSA 114.87, QED 0.51
Compound (SMILES): Nc1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)nc1
InChIKey: VHRHISVDVXQRMH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of human KDM2A preincubated for 15 mins followed by substrate addition and measured after 30 mins using Biotin-H3(28-48)K36Me2 peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 81000 nM (pChEMBL 4.090000152587891)
Descriptors: MW 303.28, ALogP 0.32, HBA 7, HBD 5, PSA 150.46, QED 0.53
Compound (SMILES): CC(=O)N1CCC(n2nc(-c3cc4cc(O)cc(Cl)c4[nH]3)c3c(N)ncnc32)CC1
InChIKey: FDJSQHVHCVOQLN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of human PI3Kbeta preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 425.88, ALogP 3.1, HBA 7, HBD 3, PSA 125.95, QED 0.45
Compound (SMILES): CN(C)C(=O)c1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)cc1
InChIKey: ZBMILIUDWNGSSH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of human KDM4C preincubated for 15 mins followed by substrate addition and measured after 15 mins using H3(1-21)K9Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 358.35, ALogP 1.05, HBA 6, HBD 4, PSA 131.86, QED 0.61
Compound (SMILES): C[C@@H](Oc1cc(NC(=O)c2cn(CCN3CCOCC3)c3cc(Br)c(C=O)nc23)ncc1C#N)c1c(Cl)cncc1Cl
InChIKey: CGZXQBNAWSMHFF-MRXNPFEDSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate in presence NADPH regenerating system
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 673.36, ALogP 5.3, HBA 10, HBD 1, PSA 135.26, QED 0.23
Compound (SMILES): Nc1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)cc1
InChIKey: JCSJQUCGCIEKPQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of human KDM4C preincubated for 15 mins followed by substrate addition and measured after 15 mins using H3(1-21)K9Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 302.29, ALogP 0.93, HBA 6, HBD 5, PSA 137.57, QED 0.52
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(N)(CCC3CC3)c3ccncc3)ccc2F)c1
InChIKey: AGVFYPDLNPHKER-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as substrate measured after 5 mins by microplate reader analysis
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 552.58, ALogP 5.53, HBA 6, HBD 3, PSA 111.85, QED 0.24
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(N)(CCC3CC3)c3ccccn3)ccc2F)c1
InChIKey: IFWBAIGKQKRJGJ-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader.
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 552.58, ALogP 5.53, HBA 6, HBD 3, PSA 111.85, QED 0.24
Compound (SMILES): COc1cccc2cc(-c3nn(C4CCOCC4)c4ncnc(N)c34)[nH]c12
InChIKey: ZEKMMWTXUQTYFE-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00459
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 364.41, ALogP 2.92, HBA 7, HBD 2, PSA 103.87, QED 0.58
Compound (SMILES): CC(C)n1nc(-c2cc3cccc(O)c3[nH]2)c2c(N)ncnc21
InChIKey: DWMSSWRQJCJQFL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human PI3Kgamma preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 308.35, ALogP 2.84, HBA 6, HBD 3, PSA 105.64, QED 0.53
Compound (SMILES): O=C(O)CNC(=O)c1nc(-c2ccccc2-c2ccccc2)ccc1O
InChIKey: CWMDDHZCTORRMW-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of human KDM2A preincubated for 15 mins followed by substrate addition and measured after 30 mins using Biotin-H3(28-48)K36Me2 peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 50200 nM (pChEMBL 4.300000190734863)
Descriptors: MW 348.36, ALogP 2.94, HBA 4, HBD 3, PSA 99.52, QED 0.66
Compound (SMILES): Cc1c(Br)cc(NC(=O)CS(=O)(=O)O)cc1Br
InChIKey: PGYFUNHIFMBZCB-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 387.05, ALogP 2.35, HBA 3, HBD 2, PSA 83.47, QED 0.78
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(O)(CCC3CC3)c3ccccn3)ccc2F)c1
InChIKey: XXMBQXWQIGCREG-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as substrate measured after 5 mins by microplate reader analysis
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 553.56, ALogP 5.56, HBA 6, HBD 3, PSA 106.06, QED 0.24
Compound (SMILES): CC(C)n1nc(-c2cc3cc(O)cc(F)c3[nH]2)c2c(N)ncnc21
InChIKey: LUKIMGGLSGHDAN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 326.34, ALogP 2.98, HBA 6, HBD 3, PSA 105.64, QED 0.52
Compound (SMILES): Nc1ncnc2c1c(-c1cc3cccc(O)c3[nH]1)nn2C1CCOCC1
InChIKey: FPBHABZEDHGIJO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 350.38, ALogP 2.61, HBA 7, HBD 3, PSA 114.87, QED 0.51
Compound (SMILES): CN[C@@H]1COc2c(S(=O)(=O)NC(=O)Nc3c4c(cc5c3CCC5)CCC4)cnn2C1
InChIKey: NDRARVKETDZHBS-AWEZNQCLSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q8R4B8
Assay: Inhibition of NLRP3 inflammasome activation in LPS and ATP-stimulated mouse whole blood assessed as reduction in IL-1beta release preincubated for 3 hrs followed by ATP stimulation and measured after 1 hr
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 431.52, ALogP 1.35, HBA 7, HBD 3, PSA 114.35, QED 0.67
Compound (SMILES): O=C(O)CNC(=O)c1nc(Nc2ccc([N+](=O)[O-])cc2)ccc1O
InChIKey: ITMKUXMZMOBJES-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of human KDM5B preincubated for 15 mins followed by substrate addition and measured after 20 mins using H3(1-21)K4Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 46300 nM (pChEMBL 4.329999923706055)
Descriptors: MW 332.27, ALogP 1.25, HBA 7, HBD 4, PSA 154.69, QED 0.45
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H]2NC(=O)[C@H](NC(=O)CN)CSSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(=O)O)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)c(I)c1)C(=O)N[C@@H](CCCN)C(=O)N[C@H](C(=O)N[C@H](CC(=O)N[C@@H](CCCNC(=N)N)C(=O)O)Cc1ccc(O)cc1)CSSC2(C)C
InChIKey: PREQDDPQCXZODC-TZHKBYJCSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Inhibition of human alpha3beta2 nAChR expressed in xenopus oocytes assessed as inhibition of Ach- induced response at -70 mV holding potential and measured for 1 to 5 days in presence of Ach stimulation by voltage-clamp based electrophysiological method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1873.97
Compound (SMILES): O=C(O)CNC(=O)c1nc(-c2cccc3ncccc23)ccc1O
InChIKey: DIURAOCBPHFCPT-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of human KDM2A preincubated for 15 mins followed by substrate addition and measured after 30 mins using Biotin-H3(28-48)K36Me2 peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 84000 nM (pChEMBL 4.079999923706055)
Descriptors: MW 323.31, ALogP 1.82, HBA 5, HBD 3, PSA 112.41, QED 0.67
Compound (SMILES): O=C(O)CNC(=O)c1nc(Nc2ccc([N+](=O)[O-])cn2)ccc1O
InChIKey: AUTPWJQNUXXRBG-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of human KDM5B preincubated for 15 mins followed by substrate addition and measured after 20 mins using H3(1-21)K4Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 87800 nM (pChEMBL 4.059999942779541)
Descriptors: MW 333.26, ALogP 0.65, HBA 8, HBD 4, PSA 167.58, QED 0.44
Compound (SMILES): Nc1ncnc2c1c(-c1cc3cc(O)ccc3[nH]1)nn2C1CCOCC1
InChIKey: BSAIWOVMAFXWGG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110Î´/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 ug/ml). Reactions are initiated by the addition of ATP containing 10 uCi of γ-32P-ATP to a final concentration 10 or 100 uM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 ul 1N HCl followed by 160 ul CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen (Storm, Amersham), and quantitated. For each compound, kinase activity is measured at 10-12 inhibitor concentrations representing two-fold dilutions from the highest concentration tested (typically, 200 uM).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 350.38, ALogP 2.61, HBA 7, HBD 3, PSA 114.87, QED 0.51
Compound (SMILES): CC(=O)N1CCC(n2nc(-c3cc4cc(O)cc(Cl)c4[nH]3)c3c(N)ncnc32)CC1
InChIKey: FDJSQHVHCVOQLN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human PI3Kgamma preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 425.88, ALogP 3.1, HBA 7, HBD 3, PSA 125.95, QED 0.45
Compound (SMILES): CN(C)C(=O)c1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)cc1
InChIKey: ZBMILIUDWNGSSH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of human KDM5B preincubated for 15 mins followed by substrate addition and measured after 20 mins using H3(1-21)K4Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 53400 nM (pChEMBL 4.269999980926514)
Descriptors: MW 358.35, ALogP 1.05, HBA 6, HBD 4, PSA 131.86, QED 0.61
Compound (SMILES): C[C@@H](Oc1cc(NC(=O)c2cn(CCN3CCOCC3)c3cc(Br)c(C=O)nc23)ncc1C#N)c1c(Cl)cncc1Cl
InChIKey: CGZXQBNAWSMHFF-MRXNPFEDSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate in presence NADPH regenerating system
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 673.36, ALogP 5.3, HBA 10, HBD 1, PSA 135.26, QED 0.23
Compound (SMILES): Nc1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)cc1
InChIKey: JCSJQUCGCIEKPQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of human KDM5B preincubated for 15 mins followed by substrate addition and measured after 20 mins using H3(1-21)K4Me3-GGK-Biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 63100 nM (pChEMBL 4.199999809265137)
Descriptors: MW 302.29, ALogP 0.93, HBA 6, HBD 5, PSA 137.57, QED 0.52
Compound (SMILES): COc1cccc2cc(-c3nn(C4CCOCC4)c4ncnc(N)c34)[nH]c12
InChIKey: ZEKMMWTXUQTYFE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition Assay: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110Î´/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 ug/ml). Reactions are initiated by the addition of ATP containing 10 uCi of γ-32P-ATP to a final concentration 10 or 100 uM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 ul 1N HCl followed by 160 ul CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen (Storm, Amersham), and quantitated. For each compound, kinase activity is measured at 10-12 inhibitor concentrations representing two-fold dilutions from the highest concentration tested (typically, 200 uM).
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 364.41, ALogP 2.92, HBA 7, HBD 2, PSA 103.87, QED 0.58
Compound (SMILES): CC(C)n1nc(-c2cc3cccc(O)c3[nH]2)c2c(N)ncnc21
InChIKey: DWMSSWRQJCJQFL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 308.35, ALogP 2.84, HBA 6, HBD 3, PSA 105.64, QED 0.53
Compound (SMILES): Cc1c(Br)cc(NC(=O)CS(=O)(=O)O)cc1Br
InChIKey: PGYFUNHIFMBZCB-UHFFFAOYSA-N
Target: Low molecular weight phosphotyrosine protein phosphatase (SINGLE PROTEIN), Mus musculus
UniProt: Q9D358
Assay: Inhibition of N-terminal His-tagged full length mouse LMW-PTP expressed in Escherichia coli BL21(DE3) by SDS PAGE based mass spectrometry analysis
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 387.05, ALogP 2.35, HBA 3, HBD 2, PSA 83.47, QED 0.78
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(O)(CCC3CC3)c3ccccn3)ccc2F)c1
InChIKey: XXMBQXWQIGCREG-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as substrate measured after 5 mins by microplate reader analysis
Measurement: IC50 = 433 nM (pChEMBL 6.360000133514404)
Descriptors: MW 553.56, ALogP 5.56, HBA 6, HBD 3, PSA 106.06, QED 0.24
Compound (SMILES): CC(C)n1nc(-c2cc3cc(O)cc(F)c3[nH]2)c2c(N)ncnc21
InChIKey: LUKIMGGLSGHDAN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 326.34, ALogP 2.98, HBA 6, HBD 3, PSA 105.64, QED 0.52
Compound (SMILES): Nc1ncnc2c1c(-c1cc3cccc(O)c3[nH]1)nn2C1CCOCC1
InChIKey: FPBHABZEDHGIJO-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00459
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 350.38, ALogP 2.61, HBA 7, HBD 3, PSA 114.87, QED 0.51
Compound (SMILES): CN[C@@H]1COc2c(S(=O)(=O)NC(=O)Nc3c4c(cc5c3CCC5)CCC4)cnn2C1
InChIKey: NDRARVKETDZHBS-AWEZNQCLSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in LPS-stimulated human whole blood assessed as reduction in ILbeta secretion in presence of monosodium urate
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 431.52, ALogP 1.35, HBA 7, HBD 3, PSA 114.35, QED 0.67
Compound (SMILES): O=C(O)CNC(=O)c1nc(Nc2ccc([N+](=O)[O-])cc2)ccc1O
InChIKey: ITMKUXMZMOBJES-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of human KDM2A preincubated for 15 mins followed by substrate addition and measured after 30 mins using Biotin-H3(28-48)K36Me2 peptide as substrate by AlphaScreen-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 332.27, ALogP 1.25, HBA 7, HBD 4, PSA 154.69, QED 0.45
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H]2NC(=O)[C@H](NC(=O)CN)CSSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(=O)O)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)c(I)c1)C(=O)N[C@@H](CCCN)C(=O)N[C@H](C(=O)N[C@H](CC(=O)N[C@@H](CCCNC(=N)N)C(=O)O)Cc1ccc(O)cc1)CSSC2(C)C
InChIKey: PREQDDPQCXZODC-TZHKBYJCSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Inhibition of human alpha3beta4 nAChR expressed in xenopus oocytes assessed as inhibition of Ach- induced response at -70 mV holding potential and measured for 1 to 5 days in presence of Ach stimulation by voltage-clamp based electrophysiological method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1873.97
Compound (SMILES): O=C(O)CNC(=O)c1nc(Nc2ccc([N+](=O)[O-])cn2)ccc1O
InChIKey: AUTPWJQNUXXRBG-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of human KDM2A preincubated for 15 mins followed by substrate addition and measured after 30 mins using Biotin-H3(28-48)K36Me2 peptide as substrate by AlphaScreen-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 333.26, ALogP 0.65, HBA 8, HBD 4, PSA 167.58, QED 0.44
Compound (SMILES): CC(=O)N1CCC(n2nc(-c3cc4cc(O)cc(Cl)c4[nH]3)c3c(N)ncnc32)CC1
InChIKey: FDJSQHVHCVOQLN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 425.88, ALogP 3.1, HBA 7, HBD 3, PSA 125.95, QED 0.45
Compound (SMILES): CN(C)C(=O)c1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)cc1
InChIKey: ZBMILIUDWNGSSH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of human KDM2A preincubated for 15 mins followed by substrate addition and measured after 30 mins using Biotin-H3(28-48)K36Me2 peptide as substrate by AlphaScreen-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 358.35, ALogP 1.05, HBA 6, HBD 4, PSA 131.86, QED 0.61
Compound (SMILES): Nc1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)cc1
InChIKey: JCSJQUCGCIEKPQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of human KDM2A preincubated for 15 mins followed by substrate addition and measured after 30 mins using Biotin-H3(28-48)K36Me2 peptide as substrate by AlphaScreen-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 302.29, ALogP 0.93, HBA 6, HBD 5, PSA 137.57, QED 0.52
Compound (SMILES): COc1cccc2cc(-c3nn(C4CCOCC4)c4ncnc(N)c34)[nH]c12
InChIKey: ZEKMMWTXUQTYFE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00750
Assay: Inhibition Assay: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110Î´/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 ug/ml). Reactions are initiated by the addition of ATP containing 10 uCi of γ-32P-ATP to a final concentration 10 or 100 uM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 ul 1N HCl followed by 160 ul CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen (Storm, Amersham), and quantitated. For each compound, kinase activity is measured at 10-12 inhibitor concentrations representing two-fold dilutions from the highest concentration tested (typically, 200 uM).
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 364.41, ALogP 2.92, HBA 7, HBD 2, PSA 103.87, QED 0.58
Compound (SMILES): CC(C)n1nc(-c2cc3cccc(O)c3[nH]2)c2c(N)ncnc21
InChIKey: DWMSSWRQJCJQFL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 308.35, ALogP 2.84, HBA 6, HBD 3, PSA 105.64, QED 0.53
Compound (SMILES): Cc1c(Br)cc(NC(=O)CS(=O)(=O)O)cc1Br
InChIKey: PGYFUNHIFMBZCB-UHFFFAOYSA-N
Target: Low molecular weight phosphotyrosine protein phosphatase (SINGLE PROTEIN), Homo sapiens
UniProt: P24666
Assay: Inhibition of His-tagged human LMW-PTP expressed in Escherichia coli BL21 using pNPP as substrate incubated for 10 mins by microplate reader based spectrophotometric analysis
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 387.05, ALogP 2.35, HBA 3, HBD 2, PSA 83.47, QED 0.78
Compound (SMILES): CC(C)n1nc(-c2cc3cc(O)cc(F)c3[nH]2)c2c(N)ncnc21
InChIKey: LUKIMGGLSGHDAN-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00459
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 326.34, ALogP 2.98, HBA 6, HBD 3, PSA 105.64, QED 0.52