lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1noc(C)c1-c1cc(C(N)=O)c2c3ccc(C(C)(C)O)cc3n(Cc3ccccc3)c2c1
InChIKey: CPMHHQADTDWUSX-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from human his-tagged BRD4 bromodomain1 (44 to 168 residues) after 60 mins by TR-FRET assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 453.54, ALogP 5.44, HBA 5, HBD 2, PSA 94.28, QED 0.37
Compound (SMILES): Cc1ccc2ncccc2c1-c1cc(-c2c(C)noc2C)cc2[nH]c(=O)[nH]c12
InChIKey: VRLSARGDMZKGFM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from his-tagged BRD4 bromodomain1 (unknown origin) incubated for 60 mins by Alphascreen assay
Measurement: IC50 < 14 nM (pChEMBL 7.854000091552734)
Descriptors: MW 370.41, ALogP 4.65, HBA 4, HBD 2, PSA 87.57, QED 0.47
Compound (SMILES): Cc1noc(C)c1-c1cnc2c(c1)nc(NC1CCOCC1)n2CC1CCCC1
InChIKey: XKIQFHHUYFCKPM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from his-tagged BRD4 bromodomain1 (unknown origin) expressed in Escherichia coli incubated for 2 hrs by HTRF assay
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 395.51, ALogP 4.48, HBA 7, HBD 1, PSA 78, QED 0.69
Compound (SMILES): Cc1noc(C)c1-c1cnc2c(-c3ccc(N)nc3)cn(CC3CCC(F)(F)CC3)c2c1
InChIKey: CDTZIRGMAPZYPZ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from his-tagged BRD4 bromodomain1 (unknown origin) expressed in Escherichia coli incubated for 2 hrs by HTRF assay
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 437.49, ALogP 5.78, HBA 6, HBD 1, PSA 82.76, QED 0.44
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(c1)C(c1ccsc1)(N1CCC[C@H](N)C1)C(=O)N2
InChIKey: REVXYXMYDPWVSB-LBOXEOMUSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from human his-tagged BRD4 bromodomain1 (1 to 477 residues) expressed in Escherichia coli incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 408.53, ALogP 3.64, HBA 6, HBD 2, PSA 84.39, QED 0.69
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(c1)C(C)(c1ccccc1)N(C)C(=O)N2
InChIKey: HPNKVGAQIXCTBD-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from His-tagged BRD4 bromodomain1 (42 to 168 residues) (unknown origin) incubated for 30 mins by Alphascreen assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 347.42, ALogP 4.7, HBA 3, HBD 1, PSA 58.37, QED 0.73
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(=O)n(C)n3c2c1OCC3c1cccnc1
InChIKey: JIWZXZCQZJYFQM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from human his-tagged BRD4 bromodomain1 after 75 mins by Alphascreen assay
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 362.39, ALogP 2.99, HBA 7, HBD 0, PSA 75.08, QED 0.55
Compound (SMILES): CCS(=O)(=O)c1ccc(OC2CCCCC2)c(-c2cn(C)c(=O)c3[nH]c(-c4cnn(C5CCNCC5)c4)cc23)c1
InChIKey: DKGDSOBOFUOPQW-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from human his-tagged BRD4 bromodomain1 (57 to 168 residues) incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 563.72, ALogP 4.83, HBA 8, HBD 2, PSA 111.01, QED 0.33
Compound (SMILES): CCS(=O)(=O)c1ccc2c(c1)-c1cn(C)c(=O)cc1OCCCCc1cc(F)ccc1O2
InChIKey: QJMMNZCQRUNWFU-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to His-tagged BRD4 bromodomain1 (unknown origin) incubated for 1 hr in presence of Europium Cryptate-labeled streptavidin by TR-FRET assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 457.52, ALogP 4.49, HBA 6, HBD 0, PSA 74.6, QED 0.57
Compound (SMILES): Cn1cc2c3c(c[nH]c3c1=O)CN(c1ncc(F)cc1F)c1ccc(CS(C)(=O)=O)cc1-2
InChIKey: YEKPMJJEOSAZID-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to His-tagged BRD4 bromodomain1 (unknown origin) incubated for 1 hr in presence of Europium Cryptate-labeled streptavidin by TR-FRET assay
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 456.47, ALogP 3.4, HBA 6, HBD 1, PSA 88.06, QED 0.51
Compound (SMILES): Cn1cc2c3c(c[nH]c(=O)c31)CN(c1ccccn1)c1ccc(CS(C)(=O)=O)cc1-2
InChIKey: KODRSHGSDLNFGJ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to His-tagged BRD4 bromodomain1 (unknown origin) (57 to 168 residues) incubated for 1 hr in presence of Europium Cryptate-labeled streptavidin by TR-FRET assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 420.49, ALogP 3.12, HBA 6, HBD 1, PSA 88.06, QED 0.55
Compound (SMILES): Cc1[nH]c(-c2cc(S(C)(=O)=O)ccc2Oc2ccc(F)cc2F)c2c1C(=O)NCC2
InChIKey: QNOJAPBYTXGBLX-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to His-tagged BRD4 bromodomain1 (unknown origin) (57 to 168 residues) incubated for 1 hr in presence of Europium Cryptate-labeled streptavidin by TR-FRET assay
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 432.45, ALogP 3.75, HBA 4, HBD 2, PSA 88.26, QED 0.66
Compound (SMILES): Cc1cn(C)c2c1C(=O)N(c1cc(Cl)c(=O)n(C)c1)[C@@H]2c1ccc(Cl)cc1
InChIKey: YGJASOUKNQFBMB-QGZVFWFLSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from his-tagged BRD4 bromodomain1 (44 to 477 residues) (unknown origin) incubated for 35 mins by TR-FRET assay
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 402.28, ALogP 4.09, HBA 4, HBD 0, PSA 47.24, QED 0.65
Compound (SMILES): Cc1cc(-c2nc3cnc(C4CCOCC4)cc3n2[C@@H](C)c2ccccc2)nn(C)c1=O
InChIKey: QNFGQQDKBYVNAS-KRWDZBQOSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from His-tagged BRD4 bromodomain1 (42 to 168 residues) (unknown origin) incubated for 30 mins by Alphascreen assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 429.52, ALogP 4, HBA 7, HBD 0, PSA 74.83, QED 0.49
Compound (SMILES): CCOc1ccc(S(=O)(=O)CC)cc1-c1cn(C)c(=O)c2ccc(-c3cnn(C)c3)cc12
InChIKey: XRQXPDFUZRIANE-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: In Vitro Enzyme Inhibition Assay: Determination of the IC50 for the heterocyclic derivative BRD4 inhibitors disclosed herein was performed as follows. His-tagged BRD4 was cloned, expressed and purified to homogeneity. Filipakopoulos et al., Nature 468:1067 (2010). BRD4 binding and inhibition was assessed by monitoring the interaction of biotinylated H4-tetraacetyl peptide (AnaSpec, H4K5/8/12/16(Ac), biotin-labeled) with the target using the AlphaScreen technology (Life Technologies). In a 384-well ProxiPlate BRD4(BD1) (2 nM final) was combined with peptide (15 nM final) in 50 mM HEPES (pH 7.3), 10 mM NaCl, 0.25 mM TCEP, 0.1% (w/v) BSA, and 0.005% (w/v) Brij-35 either in the presence of DMSO (final 0.4% DMSO) or compound dilution series in DMSO. After 20 min incubation at room temp, Alpha streptavidin donor beads and Nickel Chelate acceptor beads were added to a final concentration of 5 μg/mL. After 2 hr of equilibration, plates were read on an Envision instrument and the IC50 was calculated using a four parameter non-linear curve fit. Chemistry Example 1 (2-methyl-4-phenylisoquinolin-1-one) had an IC50 of 2.782 μM in this assay format.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 451.55, ALogP 3.8, HBA 7, HBD 0, PSA 83.19, QED 0.45
Compound (SMILES): O=C1Nc2ccc(NS(=O)(=O)C3CCCCC3)cc2C12CCC2
InChIKey: WRTGOYFDSFVHMV-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from his-tagged BRD4 bromodomain1 (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 < 150 nM (pChEMBL 6.823999881744385)
Descriptors: MW 334.44, ALogP 3.13, HBA 3, HBD 2, PSA 75.27, QED 0.89
Compound (SMILES): COc1ccc(OC(=O)N2C[C@H](C)N(C(C)=O)c3ccc(-c4cnn(C5COC5)c4)cc32)cc1
InChIKey: VFTULYRACYCIMX-INIZCTEOSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from human his-tagged BRD4 bromodomain1 (44 to 168 residues) (unknown origin) after 60 mins by Alphascreen assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 462.51, ALogP 3.89, HBA 7, HBD 0, PSA 86.13, QED 0.58
Compound (SMILES): CNC(=O)N1N=C(c2ccc(N3CC4(CCS4(=O)=O)C3)cc2)c2cc(OC)c(OC)cc2CC1C
InChIKey: PSIDZHBBFPTUGA-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated tetra-acetylated histone H4 from his-tagged BRD4 bromodomain1 (67 to 152 residues) (unknown origin) incubated for 1 hr at 22 degC followed by overnight incubation at 4degC by TR-FRET assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 498.61, ALogP 2.42, HBA 7, HBD 1, PSA 100.54, QED 0.7
Compound (SMILES): Cc1[nH]c(-c2ccccc2NC2C3CC4CC(C3)CC2C4)cc1C(N)=O
InChIKey: YKOVCVLNIAAKKI-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to His-tagged BRD4 bromodomain1 (unknown origin) incubated for 1 hr in presence of Europium Cryptate-labeled streptavidin by TR-FRET assay
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 349.48, ALogP 4.33, HBA 2, HBD 3, PSA 70.91, QED 0.77
Compound (SMILES): CC1=C(Nc2ccc(C(=O)Nc3ccccc3C)cc2Cl)CCC1=O
InChIKey: CCGXMPICFYXVTO-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of FITC-labeled MS417 from BRD4 bromodomain 1 (unknown origin) after 1 hr by fluorescence anisotropy
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 354.84, ALogP 4.95, HBA 3, HBD 2, PSA 58.2, QED 0.82
Compound (SMILES): CCCS(=O)(=O)c1nc(NC2CC2)cc(-c2ccc3c(ccn3C3CC(C)(C)NC(C)(C)C3)c2)n1
InChIKey: XVECNLUKQDKOST-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Binding affinity to CECR2 (unknown origin) by isothermal titration calorimetry
Measurement: Kd = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 495.69, ALogP 5.34, HBA 7, HBD 2, PSA 88.91, QED 0.43
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1
InChIKey: CZNFQLDDPKKPMX-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged JARID1A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 203.2, ALogP 1.18, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): COc1ccc(-c2c(-c3cc(C(=O)O)ccn3)ncn2C)cc1
InChIKey: XGBOARWPNSLLHZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 309.33, ALogP 2.86, HBA 5, HBD 1, PSA 77.24, QED 0.8
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1ccc(OCC2CC2)cc1
InChIKey: MWJQMQXBUJYTHO-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 349.39, ALogP 3.64, HBA 5, HBD 1, PSA 77.24, QED 0.74
Compound (SMILES): Cn1cnc(-c2cc(-c3nnn[nH]3)ccn2)c1
InChIKey: JYEUQFOUZAUNTD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 227.23, ALogP 0.66, HBA 6, HBD 1, PSA 85.17, QED 0.69
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(Cl)cc2)c1
InChIKey: SMXDPQZYSIFABV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 329.74, ALogP 3.2, HBA 5, HBD 1, PSA 77.24, QED 0.78
Compound (SMILES): COC(=O)c1ccnc(-n2nccc2OCc2ccc(Cl)cc2)c1
InChIKey: CDSIWRGJSKHJRV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of KDM5A in human ZR-75-1 cells assessed as reduction in H3K4me3 demethylation incubated for 72 hrs by fluorometric immunoassay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 343.77, ALogP 3.29, HBA 6, HBD 0, PSA 66.24, QED 0.66
Compound (SMILES): Cc1cc(Cl)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: PSOBPHXKKHPWMU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 343.77, ALogP 3.51, HBA 5, HBD 1, PSA 77.24, QED 0.77
Compound (SMILES): O=C(O)c1ccnc(-n2ncc(CCO)c2OCc2ccc(F)cc2)c1
InChIKey: MAYCQAAYKTWJKJ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged JARID1A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 357.34, ALogP 2.22, HBA 6, HBD 2, PSA 97.47, QED 0.67
Compound (SMILES): O=C(O)c1ccncc1NCC1CCCc2cc(Oc3ccccc3)ccc21
InChIKey: RUIDTLFWDJICDV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET): The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 min, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hr incubation at rt.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 374.44, ALogP 5.1, HBA 4, HBD 2, PSA 71.45, QED 0.63
Compound (SMILES): O=C(O)c1ccncc1NCC12CC3CC(CC(C3)C1)C2
InChIKey: TUXVCHDESZTZON-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Enzymatic Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 286.38, ALogP 3.41, HBA 3, HBD 2, PSA 62.22, QED 0.89
Compound (SMILES): O=C(O)c1ccncc1Nc1nn(C2CCCC2)c2ccc(F)cc12
InChIKey: LJHFNRZRNINLGH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 340.36, ALogP 4.13, HBA 5, HBD 2, PSA 80.04, QED 0.75
Compound (SMILES): Cn1nc(Nc2cnccc2C(=O)O)c2cccnc21
InChIKey: ZNABVSMDKOBVOS-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 269.26, ALogP 1.81, HBA 6, HBD 2, PSA 92.93, QED 0.75
Compound (SMILES): CC(C)Cn1nc(Nc2cnccc2C(=O)NC#N)c2cc(F)ccc21
InChIKey: HHHITATYTCPWBZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 352.37, ALogP 3.18, HBA 6, HBD 2, PSA 95.63, QED 0.54
Compound (SMILES): COc1cc(COc2cc3nccc(C(=O)O)c3[nH]2)ccc1Cl
InChIKey: VTUTUCVVSXMISL-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 332.74, ALogP 3.5, HBA 4, HBD 2, PSA 84.44, QED 0.75
Compound (SMILES): O=C(O)c1ccnc2cc(OCc3ccc(Cl)c(OCC4CC4)c3)[nH]c12
InChIKey: RHPSPIUSPOTEGT-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 372.81, ALogP 4.28, HBA 4, HBD 2, PSA 84.44, QED 0.65
Compound (SMILES): O=C(O)c1ccnc2cc(OCc3ccc(Cl)c(OC(F)(F)F)c3)[nH]c12
InChIKey: ZMBZYRJHWCFIQA-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected sf9 cells using biotin-H3K4me3 substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 386.71, ALogP 4.39, HBA 4, HBD 2, PSA 84.44, QED 0.68
Compound (SMILES): Cn1cnc(-c2nccc3c(O)nc(OCCCC(F)(F)F)nc23)c1
InChIKey: GVIVKUKLHYWHES-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of KDM5A (unknown origin)
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 353.3, ALogP 2.85, HBA 7, HBD 1, PSA 85.95, QED 0.71
Compound (SMILES): O=C(N[C@@H](CCCCN[C@@H]1C[C@H]1c1ccc(F)cc1)C(=O)NCc1ccc(F)cc1)c1ccccc1
InChIKey: ITKLCEURKLAMKI-GMQQYTKMSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant KDM1A using H3 (1 to 21 residues)-K4me2 peptide substrate by fluorescence coupling enzyme assay
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 491.58, ALogP 4.7, HBA 3, HBD 3, PSA 70.23, QED 0.32
Compound (SMILES): Cc1ncc(NC(=O)c2cccc([C@@H]3C[C@H]3NC3CCOCC3)c2)s1
InChIKey: JSKGRNMNSFBKJQ-DLBZAZTESA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of MAO-A (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins by MAO-Glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 357.48, ALogP 3.33, HBA 5, HBD 2, PSA 63.25, QED 0.86
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3ccc([C@@H]4C[C@]4(N)CCc4ccccc4)cc3)cc2)CC1
InChIKey: VNZUIBQXPADFGI-LMSSTIIKSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant KDM1A expressed in Escherichia coli using H3K4me peptide substrate preincubated for 15 mins followed substrate addition measured after 12 mins by peroxidase coupled enzyme assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 454.62, ALogP 4.51, HBA 4, HBD 2, PSA 61.6, QED 0.55
Compound (SMILES): CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(OC(=O)OC(C)(C)C)cc1
InChIKey: VVFYDJJSFHIMKO-LSDHHAIUSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of KDM1A (unknown origin) by cell based assay
Measurement: IC50 = 21250 nM (pChEMBL 4.670000076293945)
Descriptors: MW 349.43, ALogP 4.38, HBA 5, HBD 1, PSA 73.86, QED 0.65
Compound (SMILES): CC(C)S(=O)(=O)Nc1cccc(-c2ccc([C@H]3C[C@@H]3N)cc2)c1
InChIKey: UNMUJLUQVFHXSH-MSOLQXFVSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant human N-terminal GST-tagged KDM1A expressed in Escherichia coli using H3K4me2 as substrate preincubated for 15 mins followed by substrate addition measured after 1 hr by peroxidase coupled enzyme assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 330.45, ALogP 3.32, HBA 3, HBD 2, PSA 72.19, QED 0.88
Compound (SMILES): O=S(=O)(c1ccc2[nH]c(Nc3cc(Cl)ccc3O)nc2c1)N1CCOCC1
InChIKey: BFCHTJAXNSVMOE-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of Histone Demethylase Activity: Inhibition of LSD activity can be determined by a variety of both in vitro and in vivo methods known to one skilled in the art. For example, enzymatic activity can be determined in in vitro enzyme assay systems. In various embodiments, the enzymatic activity of LSD1 can be determined in a spectrophometric assay. Briefly, the assay is based on the multistep enzymatic reaction in which LSD1 first produces H2O2 during the demethylation of lysine 4 on a peptide corresponding to the first 21 amino acids of the N-terminal tail of histone H3. In the presence of horseradish peroxidase, the H2O2 produced reacts with ADHP to produce the highly fluorescent compound resorufin that can be analyzed with an excitation wavelength of 530-540 nm and an emission wavelength of 585-595 nm. The assay requires a source of LSD1 enzyme, either purified from natural sources (e.g. a tissue or cultured cells), isolated as a recombinantly expressed protein, or as a unpurified protein in whole cell extracts. In one embodiment, the disclosed compounds exhibit inhibition of LSD protein activity with an IC50 in an EMSA assay of less than about 300 mM, less than about 100 mM, less than about 50 mM, less than about 10 mM, less than about 1 mM, less than about 500 nM, or of less than about 100 nM. In another embodiment, the disclosed compounds exhibit inhibition of LSD1 protein activity with an IC50 in an EMSA assay of less than about 300 mM, less than about 100 mM, less than about 50 mM, less than about 10 mM, less than about 1 mM, less than about 500 nM, or of less than about 100 nM. In another embodiment, the disclosed compounds exhibit inhibition of LSD2 protein activity with an IC50 in an EMSA assay of less than about 300 mM, less than about 100 mM, less than about 50 mM, less than about 10 mM, less than about 1 mM, less than about 500 nM, or of less than about 100 nM.
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 408.87, ALogP 2.69, HBA 6, HBD 3, PSA 107.55, QED 0.57
Compound (SMILES): Cc1ccc(-c2cnc(NC[C@H]3CCNC3)nc2-c2ccc(C#N)cc2)cc1
InChIKey: YCCRZPBTSZSNQO-SFHVURJKSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of full length human KDM1A expressed in Escherichia coli using biotin-H3K4me1 as substrate incubated for 1 hr by TR-FRET assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 369.47, ALogP 4.01, HBA 5, HBD 2, PSA 73.63, QED 0.71
Compound (SMILES): Cc1ccc(NC(=O)CCC(=O)OCC(=O)c2ccc(-c3ccccc3)cc2)cc1Cl
InChIKey: UTUPQHXDVDJNQY-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human N-terminal KDM1A (151 to 852 residues) using H3 (l to 21 residues)-K4me2 peptide substrate preincubated for 15 mins followed by substrate addition measured after 1 hr by peroxidase coupled enzyme assay
Measurement: IC50 = 2410 nM (pChEMBL 5.619999885559082)
Descriptors: MW 435.91, ALogP 5.46, HBA 4, HBD 1, PSA 72.47, QED 0.38
Compound (SMILES): CSCCc1nc(-c2cc(N)ccc2Cl)oc1C
InChIKey: MMICNUMTHQLBEV-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant KDM1A using H3K4me2 and ADHP substrate assessed as inhibition of resorufin formation by peroxidase coupled enzyme assay
Measurement: IC50 = 10100 nM (pChEMBL 5)
Descriptors: MW 282.8, ALogP 3.79, HBA 4, HBD 1, PSA 52.05, QED 0.87
Compound (SMILES): C/C(=C\CC/C(C)=C/C(=O)O)CC/C=C(\C)CCCC(C)C
InChIKey: LKLFDSRDWOXLRH-OZFNKYQOSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant KDM1A using H3K4me2 and ADHP substrate assessed as inhibition of resorufin formation by peroxidase coupled enzyme assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 306.49, ALogP 6.3, HBA 1, HBD 1, PSA 37.3, QED 0.36
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)N)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](C)C(N)=O
InChIKey: SOENCYTZSABTHN-LSFKTUMCSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant KDM1A expressed in Escherichia coli using H3K4me as substrate by peroxidase coupled enzyme assay
Measurement: Ki = 1800 nM (pChEMBL 5.75)
Descriptors: MW 2253.65
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)O)C(C)C
InChIKey: IFBOJZGYDJWXEX-NVTBKHRPSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant His-tagged KDM1A (171 to 836 residues) using H3K4me2 as substrate by peroxidase coupled enzyme assay
Measurement: Ki = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 2386.71
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CCCCCCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: JRPNOMILURHFKV-KWUOZLKKSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of S0586[K4]hpp from human NPY4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ by flow cytometric analysis
Measurement: Ki = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 1676.01
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CCCN/C(N)=N/C(=O)NCCCCN)NC(=O)[C@@H](N)CC(=O)O)C(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: APPMXIIOSPZAMH-HJYQNBTFSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Agonist activity at human AT1 receptor transfected in CHO cells co-expressing Galpha16-mtAEQ assessed as induction of intracellular Ca2+ mobilization by bioluminescence assay
Measurement: EC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 1160.35
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CCCN/C(N)=N/C(=O)NCCOCCOCCN)NC(=O)[C@@H](N)CC(=O)O)C(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: TVCTVZBYROZMPQ-NHMPIGKUSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Agonist activity at human AT1 receptor transfected in CHO cells co-expressing Galpha16-mtAEQ assessed as induction of intracellular Ca2+ mobilization by bioluminescence assay
Measurement: EC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 1220.4
Compound (SMILES): CCOC(=O)C1=C(C)NC(=O)CC1c1ccco1
InChIKey: KQWVICMSFKEFBG-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 2536 nM (pChEMBL 5.599999904632568)
Descriptors: MW 249.27, ALogP 1.72, HBA 4, HBD 1, PSA 68.54, QED 0.83
Compound (SMILES): CCOC(=O)C1=C(C)Nc2nccn2C1c1ccco1
InChIKey: MUUZJZYBLWYVIJ-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 273.29, ALogP 2.33, HBA 6, HBD 1, PSA 69.29, QED 0.87
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2ccco2)n2ccnc2N1
InChIKey: XSFNZYDKVKNNMU-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 85.6 nM (pChEMBL 7.070000171661377)
Descriptors: MW 287.32, ALogP 2.72, HBA 6, HBD 1, PSA 69.29, QED 0.88
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2ccoc2)n2ccnc2N1
InChIKey: DSMIPQLMUFQGPC-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 276.9 nM (pChEMBL 6.559999942779541)
Descriptors: MW 287.32, ALogP 2.72, HBA 6, HBD 1, PSA 69.29, QED 0.88
Compound (SMILES): CCOC(=O)C1=C(C)Nc2nccn2C1c1cccs1
InChIKey: BQKSFNGEGLUOBZ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]NECA from human Adenosine A3 receptor expressed in HeLa cells after 30 mins
Measurement: Ki = 4611 nM (pChEMBL 5.340000152587891)
Descriptors: MW 289.36, ALogP 2.8, HBA 6, HBD 1, PSA 56.15, QED 0.88
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2cccs2)n2ccnc2N1
InChIKey: DMYPCQZAJQVUOT-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 728.1 nM (pChEMBL 6.139999866485596)
Descriptors: MW 303.39, ALogP 3.19, HBA 6, HBD 1, PSA 56.15, QED 0.88
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2ccsc2)n2ccnc2N1
InChIKey: HVEXNSRVAXILPN-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 847.3 nM (pChEMBL 6.070000171661377)
Descriptors: MW 303.39, ALogP 3.19, HBA 6, HBD 1, PSA 56.15, QED 0.88
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2ccco2)n2ncnc2N1
InChIKey: OGERYLQRXYIBML-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 55.6 nM (pChEMBL 7.25)
Descriptors: MW 288.31, ALogP 2.11, HBA 7, HBD 1, PSA 82.18, QED 0.87
Compound (SMILES): CCOC(=O)C1=C(C)Nc2ncnn2C1c1ccoc1
InChIKey: SLWSHEZJGFQJLF-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 602.4 nM (pChEMBL 6.21999979019165)
Descriptors: MW 274.28, ALogP 1.72, HBA 7, HBD 1, PSA 82.18, QED 0.86
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2ccoc2)n2ncnc2N1
InChIKey: SJJQXWXECZMAGT-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 350.5 nM (pChEMBL 6.460000038146973)
Descriptors: MW 288.31, ALogP 2.11, HBA 7, HBD 1, PSA 82.18, QED 0.87
Compound (SMILES): CCOC(=O)C1=C(C)Nc2ncnn2C1c1ccsc1
InChIKey: XMSGHXKBLXWENB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 699.2 nM (pChEMBL 6.159999847412109)
Descriptors: MW 290.35, ALogP 2.19, HBA 7, HBD 1, PSA 69.04, QED 0.88
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2ccsc2)n2ncnc2N1
InChIKey: DVHQDGGSQYSMJK-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 816.7 nM (pChEMBL 6.090000152587891)
Descriptors: MW 304.38, ALogP 2.58, HBA 7, HBD 1, PSA 69.04, QED 0.88
Compound (SMILES): CCOC(=O)C1=C(C)Nc2nc3ccccc3n2C1c1ccco1
InChIKey: YAACPROIKGSQEL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 12.03 nM (pChEMBL 7.920000076293945)
Descriptors: MW 323.35, ALogP 3.48, HBA 6, HBD 1, PSA 69.29, QED 0.75
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2ccco2)n2c(nc3ccccc32)N1
InChIKey: NYHLRBMDXQBOIB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 3.49 nM (pChEMBL 8.460000038146973)
Descriptors: MW 337.38, ALogP 3.87, HBA 6, HBD 1, PSA 69.29, QED 0.73
Compound (SMILES): CCOC(=O)C1=C(C)Nc2nc3ccccc3n2C1c1ccoc1
InChIKey: YDWNLPRFWUXVCV-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 20.6 nM (pChEMBL 7.690000057220459)
Descriptors: MW 323.35, ALogP 3.48, HBA 6, HBD 1, PSA 69.29, QED 0.75
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2ccoc2)n2c(nc3ccccc32)N1
InChIKey: CVPPUYGSPNIDQH-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) expressed in insect cell microsomes using dibenzylfluorescein substrate by fluorescence based assay
Measurement: IC50 = 2680 nM (pChEMBL 5.570000171661377)
Descriptors: MW 337.38, ALogP 3.87, HBA 6, HBD 1, PSA 69.29, QED 0.73
Compound (SMILES): CCOC(=O)C1=C(C)Nc2nc3ccccc3n2C1c1cccs1
InChIKey: DWNFGSHYXMLWFM-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 484.6 nM (pChEMBL 6.320000171661377)
Descriptors: MW 339.42, ALogP 3.95, HBA 6, HBD 1, PSA 56.15, QED 0.73
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2cccs2)n2c(nc3ccccc32)N1
InChIKey: DUINPKHJLSSVHN-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 371.2 nM (pChEMBL 6.429999828338623)
Descriptors: MW 353.45, ALogP 4.34, HBA 6, HBD 1, PSA 56.15, QED 0.71
Compound (SMILES): CCOC(=O)C1=C(C)Nc2nc3ccccc3n2C1c1ccsc1
InChIKey: FRCVFFDEURQUBC-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 29.71 nM (pChEMBL 7.53000020980835)
Descriptors: MW 339.42, ALogP 3.95, HBA 6, HBD 1, PSA 56.15, QED 0.73
Compound (SMILES): CC1=C(C(=O)OC(C)C)C(c2ccsc2)n2c(nc3ccccc32)N1
InChIKey: FLDPOALIHQWAGV-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human Adenosine A2B receptor expressed in HEK293 cells after 30 mins
Measurement: Ki = 29.34 nM (pChEMBL 7.53000020980835)
Descriptors: MW 353.45, ALogP 4.34, HBA 6, HBD 1, PSA 56.15, QED 0.71
Compound (SMILES): O=C(N[C@H]1COc2ccccc2NC1=O)c1cc(Cc2ccccc2)on1
InChIKey: HMBAEAQKWTXBHE-KRWDZBQOSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIP1 in human U937 cells assessed as inhibition of TNF/zVAD.fmk induced necroptosis after 24 hrs by Cell titer-Glo luminescence assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 363.37, ALogP 2.39, HBA 5, HBD 2, PSA 93.46, QED 0.74
Compound (SMILES): O=C(N[C@H]1COc2ccccc2NC1=O)c1cccc(Oc2ccccc2)c1
InChIKey: AWXYMMISTIIAIH-IBGZPJMESA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIP1 in human U937 cells assessed as inhibition of TNF/zVAD.fmk induced necroptosis after 24 hrs by Cell titer-Glo luminescence assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 374.4, ALogP 3.61, HBA 4, HBD 2, PSA 76.66, QED 0.73
Compound (SMILES): CCCCCc1cc(C(=O)N[C@H]2COc3ccccc3NC2=O)n[nH]1
InChIKey: KSXXLKPPWYRQCT-HNNXBMFYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIP1 in human U937 cells assessed as inhibition of TNF/zVAD.fmk induced necroptosis after 24 hrs by Cell titer-Glo luminescence assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 342.4, ALogP 2.27, HBA 4, HBD 3, PSA 96.11, QED 0.7
Compound (SMILES): O=C(N[C@@H]1COc2ccccc2NC1=O)c1cc(Cc2ccccc2)on1
InChIKey: HMBAEAQKWTXBHE-QGZVFWFLSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIP1 in human U937 cells assessed as inhibition of TNF/zVAD.fmk induced necroptosis after 24 hrs by Cell titer-Glo luminescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 363.37, ALogP 2.39, HBA 5, HBD 2, PSA 93.46, QED 0.74
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2cc(Cc3ccccc3)on2)COc2ccccc21
InChIKey: KNOUWGGQMADIBV-KRWDZBQOSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Competitive inhibition of human RIP1 (1 to 375 residues) in presence of increasing ATP by ADP-Glo reagent based assay
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 377.4, ALogP 2.42, HBA 5, HBD 1, PSA 84.67, QED 0.75
Compound (SMILES): O=C(N[C@H]1CS(=O)(=O)c2ccccc2NC1=O)c1cc(Cc2ccccc2)on1
InChIKey: GCXSDJBPWVZLCU-KRWDZBQOSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIP1 (1 to 375 residues) after 4 hrs by ADP-Glo reagent based assay
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 411.44, ALogP 1.79, HBA 6, HBD 2, PSA 118.37, QED 0.68
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2cc(Cc3ccccc3)on2)CSc2ccccc21
InChIKey: KXBWKWXLJDJUTG-KRWDZBQOSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIP1 (1 to 375 residues) after 4 hrs by ADP-Glo reagent based assay
Measurement: IC50 = 0.94 nM (pChEMBL 9.029999732971191)
Descriptors: MW 393.47, ALogP 3.13, HBA 5, HBD 1, PSA 75.44, QED 0.74
Compound (SMILES): O=C(N[C@H]1CNc2ccccc2NC1=O)c1cc(Cc2ccccc2)on1
InChIKey: XLSNJTZNUHLDQC-SFHVURJKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIP1 (1 to 375 residues) after 4 hrs by ADP-Glo reagent based assay
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 362.39, ALogP 2.43, HBA 5, HBD 3, PSA 96.26, QED 0.66
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2cc(Cc3ccccc3)on2)CNc2ccccc21
InChIKey: FILOHPAPJRJFDF-SFHVURJKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q60855
Assay: Binding affinity to mouse RIP1 (1 to 378 residues) preincubated for 10 mins measured after 20 mins by fluorescence polarization assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 376.42, ALogP 2.45, HBA 5, HBD 2, PSA 87.47, QED 0.73
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2cc(Cc3cccc(C4(C(F)(F)F)N=N4)c3)[nH]n2)COc2ccccc21
InChIKey: ZMNTWFPENWVBQI-KRWDZBQOSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Binding affinity to Flag-tagged human RIP1 (1 to 324 residues) at 10 uM after 30 mins by fluorescence polarization assay
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 484.44, ALogP 3.34, HBA 6, HBD 2, PSA 112.04, QED 0.58
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2cc(Cc3ccccc3)on2)CCc2cc(C3(C(F)(F)F)N=N3)ccc21
InChIKey: SIDIZJFULUPVLJ-SFHVURJKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Binding affinity to Flag-tagged human RIP1 (1 to 324 residues) at 10 uM after 30 mins by fluorescence polarization assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 483.45, ALogP 4.15, HBA 6, HBD 1, PSA 100.16, QED 0.59
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2cc(Cc3ccccc3)[nH]n2)COc2ccccc21
InChIKey: NIAHVVIUZUZDFS-KRWDZBQOSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of Flag-tagged human RIP1 (1 to 324 residues) after 30 mins by ADP-Glo reagent based assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 376.42, ALogP 2.15, HBA 4, HBD 2, PSA 87.32, QED 0.73
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2cc(Cc3ccccc3)on2)CCc2ccccc21
InChIKey: QIFUAERRNRWOHL-SFHVURJKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of RIP1 in human U937 cells assessed as reduction in TNFalpha/QVD-Oph-induced necrosis after 24 hrs by Cell Titer-Glo luminescent cell viability assay
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 375.43, ALogP 2.97, HBA 4, HBD 1, PSA 75.44, QED 0.76
Compound (SMILES): CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)[C@@H]1Cc2ccccc2CN1C(=O)CCC(=O)c1ccccc1)C(=O)NCC(c1ccccc1)c1ccccc1
InChIKey: GNVWJABJQSHDON-YDAXCOIMSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Positive allosteric modulation of human CXCR3 expressed in HEK293T cell membranes after 30 mins by [35S]GTPgammaS incorporation assay
Measurement: EC50 = 1318.26 nM (pChEMBL 5.880000114440918)
Descriptors: MW 744.93, ALogP 6.73, HBA 6, HBD 3, PSA 133.91, QED 0.09
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)c3ccc(C(=O)O)o3)[nH]c3c(-c4c(C)nn(C)c4C)c(Cl)ccc23)cc(C)c1Cl
InChIKey: ADAKEJQIRIAPEC-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of mixture of 4- and 5-(N-(7-(1-(2-((6-(3-carboxy-4-(6-hydroxy-3-oxo-3Hxanthen-9-yl)benzamido)hexyl)amino)-2-oxoethyl)-3,5-dimethyl-1H-pyrazol-4-yl)-6-chloro-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-1H-indole-2-carbonyl)sulfamoyl)furan-2-carboxylic acid from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA assay
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 673.58, ALogP 6.53, HBA 8, HBD 3, PSA 156.52, QED 0.14
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)c3cccc(CNC(=O)c4ccccc4C(F)(F)F)c3)[nH]c3c(-c4c(C)nn(C)c4C)c(Cl)ccc23)cc(C)c1Cl
InChIKey: WINJOECYQHXQMQ-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Binding affinity to Bcl-xL (unknown origin) after 1.5 hrs by FPA assay
Measurement: Ki = 4467 nM (pChEMBL 5.349999904632568)
Descriptors: MW 840.75, ALogP 9.19, HBA 7, HBD 3, PSA 135.18, QED 0.11
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)c3cccc(CNC(=O)c4cccc(C(F)(F)F)c4)c3)[nH]c3c(-c4c(C)nn(C)c4C)c(Cl)ccc23)cc(C)c1Cl
InChIKey: MKRUMIFVVFWNJZ-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Binding affinity to Bcl-xL (unknown origin) after 1.5 hrs by FPA assay
Measurement: Ki = 12854 nM (pChEMBL 4.889999866485596)
Descriptors: MW 840.75, ALogP 9.19, HBA 7, HBD 3, PSA 135.18, QED 0.11