lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C=CC(=O)Nc1cccc(NC(=O)Nc2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)c1
InChIKey: LZKHGZOJRVSIFE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human GST-tagged wild-type EGFR cytoplasmic domain (668 to 1210 residues) expressed in baculovirus expression system using tyrosine04 peptide as substrate after 60 mins in presence of ATP by Z-LYTE assay
Measurement: IC50 = 644 nM (pChEMBL 6.190000057220459)
Descriptors: MW 459.51, ALogP 3.83, HBA 7, HBD 4, PSA 120.51, QED 0.4
Compound (SMILES): Cc1ccc(/C=N/NC(=O)N2CCc3ncnc(Nc4cccc(C(F)(F)F)c4)c3C2)cc1
InChIKey: NLAXMHQWTOCNAO-XKJRVUDJSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of glycosylated human ATX using FS-3 as substrate preincubated for 45 mins under shaking condition followed by substrate addition and measured after 45 mins by fluorescence assay
Measurement: IC50 = 29.1 nM (pChEMBL 7.539999961853027)
Descriptors: MW 454.46, ALogP 4.65, HBA 5, HBD 2, PSA 82.51, QED 0.44
Compound (SMILES): CCc1nc(C)nc(CC)c1N1CCCn2c1nc1c(Cl)ccc(C(OC(F)F)C(F)(F)F)c12
InChIKey: VNGQLFDQQZOYCQ-UHFFFAOYSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: Displacement of ovine [125-I]-CRF from human CRF1 receptor expressed in CHO cell membranes after 1.5 hrs by liquid scintillation counting method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 503.9, ALogP 6.3, HBA 6, HBD 0, PSA 56.07, QED 0.37
Compound (SMILES): CCCOC1CCN(C(=O)Cc2cc(C3NC(=O)NC(C)=C3C(=O)Nc3ccc4[nH]ncc4c3)ccc2F)C1
InChIKey: IGTRGZRRSHVLHM-UHFFFAOYSA-N
Target: Beta-adrenergic receptor kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25098
Assay: Inhibition of GRK2 (unknown origin) preincubated for 10 mins followed by peptide substrate and ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 534.59, ALogP 3.54, HBA 5, HBD 4, PSA 128.45, QED 0.35
Compound (SMILES): Cc1cn2c(-c3cn[nH]c3)cnc2c(Nc2cc(C(c3ccccn3)N3CCCCC3)ns2)n1
InChIKey: JGQWCDPUDLKBMX-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of Aurora B (unknown origin) using Tamra-PKAtide as substrate by fluorescence polarization assay
Measurement: IC50 < 13 nM (pChEMBL 7.886000156402588)
Descriptors: MW 471.59, ALogP 4.6, HBA 9, HBD 2, PSA 99.92, QED 0.37
Compound (SMILES): O=c1c(-c2cc[nH]n2)n[nH]c2c(-c3cccc(F)c3)cnn12
InChIKey: XOBFTVGIIXQBGL-UHFFFAOYSA-N
Target: GABA-A receptor; alpha-1/beta-2/gamma-2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P62813
Assay: Displacement of [3H]Ro15-1788 from recombinant rat GABAAalpha1/beta2/gamma2 receptor after 90 mins by liquid scintillation counting method
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 296.26, ALogP 1.61, HBA 5, HBD 2, PSA 91.73, QED 0.59
Compound (SMILES): O=C(NO)C1CN(C(=O)c2ccc(-c3ccccc3)cc2)CCN1S(=O)(=O)c1ccccc1
InChIKey: RBKZNQGTAVDVHA-UHFFFAOYSA-N
Target: Falcilysin (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: Q76NL8
Assay: Inhibition of Plasmodium falciparum 3D7 FLN (55 to 1193 residues) expressed in Escherichia coli BL21 using Dabcyl-HKRHSFRMRG-EDANS as substrate preincubated for 5 mins followed by substrate addition measured for 10 mins by fluorescence assay
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 465.53, ALogP 2.37, HBA 5, HBD 2, PSA 107.02, QED 0.44
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H](O)[C@H](N)Cc1ccccc1)C(=O)NCCOCCOCCOCCNC(=O)c1ccc(S(=O)(=O)CC(C)(O)C(=O)Nc2ccc(C#N)c(C(F)(F)F)c2)cc1
InChIKey: PIRRWGXSGGCAEW-OGBWKRBHSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Displacement of [17-alpha-methyl-H-3] mibolerone from wild-type androgen receptor (unknown origin) expressed in human Freestyle293F cells measured after 3 hrs
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 921, ALogP 2.1, HBA 13, HBD 7, PSA 268.5, QED 0.06
Compound (SMILES): CC(=O)N[C@@H](C)/C=C/c1ccc(Oc2ccc(OCC3CC3)cc2Cl)nn1
InChIKey: BYNDGTWELLDLAU-YIALFULDSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 387.87, ALogP 4.25, HBA 5, HBD 1, PSA 73.34, QED 0.73
Compound (SMILES): CNC(=O)c1ccc(Sc2ccc(NC(=S)Nc3cccc(C)c3)cc2)nc1
InChIKey: MCYIOJVIZPEBGT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf V600E mutant (unknown origin) using MEK1 as substrate measured after 2 hrs by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.55, ALogP 4.71, HBA 4, HBD 3, PSA 66.05, QED 0.53
Compound (SMILES): COC1=CC(=O)/C(=C(\C=C\c2ccccc2)OC)C1=O
InChIKey: FITVJPYUOAZKPN-PBMBQWDMSA-N
Target: Protein farnesyltransferase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49354
Assay: Inhibition of FPTase (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 270.28, ALogP 2.28, HBA 4, HBD 0, PSA 52.6, QED 0.48
Compound (SMILES): CC(C)C[C@H](NC(=O)c1ccc(-c2ccccc2)cc1)C(=O)NC1(C#N)CC1
InChIKey: HKCJMGIUXGADPK-FQEVSTJZSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of human cathepsin S
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 375.47, ALogP 3.67, HBA 3, HBD 2, PSA 81.99, QED 0.77
Compound (SMILES): CC(C)c1cc(C(=O)N2CC(F)C2)cc(C(C)C)c1O
InChIKey: AGLDXFXZJFGKRL-UHFFFAOYSA-N
Target: Glycine receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23415
Assay: Positive allosteric modulation of GlyRalpha1 (unknown origin) assessed as potentiation of glycine-induced response
Measurement: EC50 = 0.43 nM (pChEMBL 9.369999885559082)
Descriptors: MW 279.36, ALogP 3.43, HBA 2, HBD 1, PSA 40.54, QED 0.92
Compound (SMILES): CC(C)(C)c1cc(C(C)(C)C)c(O)c(C(=O)O)c1O
InChIKey: FVQBNGXOHJYGMZ-UHFFFAOYSA-N
Target: Glycine receptor alpha-3/beta (PROTEIN COMPLEX), Homo sapiens
UniProt: P48167
Assay: Positive allosteric modulation of human GlyRalpha3beta expressed in CHO cells assessed as potentiation of EC20 glycine-induced ion flux by HT assay
Measurement: EC50 = 13.49 nM (pChEMBL 7.869999885559082)
Descriptors: MW 266.34, ALogP 3.39, HBA 3, HBD 3, PSA 77.76, QED 0.73
Compound (SMILES): O=C(O)CC1CCCc2c1n(Cc1ccc(C(F)(F)F)cc1)c1c(C(F)(F)F)cc(F)cc21
InChIKey: XXVZVTOALZJPQU-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of PDE2 (unknown origin)
Measurement: IC50 = 233 nM (pChEMBL 6.630000114440918)
Descriptors: MW 473.39, ALogP 6.76, HBA 2, HBD 1, PSA 42.23, QED 0.43
Compound (SMILES): C=CC(=O)NCCCC[C@H](NC(=O)Cc1ccccc1)C(=O)N1CCN(c2cccc([N+](=O)[O-])n2)CC1
InChIKey: NIVSSMKVJURCCV-NRFANRHFSA-N
Target: Protein-glutamine gamma-glutamyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P21980
Assay: Inhibition of human TGase 2 using R-I-Cad/DMC as substrate preincubated for 5 mins followed by substrate addition measured at 30 secs interval over 900 secs by fluorescence anisotropy assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 508.58, ALogP 1.84, HBA 7, HBD 2, PSA 137.78, QED 0.19
Compound (SMILES): NC(=O)c1cccc2c(NCc3c(F)cccc3C(F)(F)F)nc(N3Cc4cn[nH]c4C3)nc12
InChIKey: MQPWNHHLCSGLJG-UHFFFAOYSA-N
Target: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28907
Assay: Inhibition of recombinant human CD38 extracellular domain expressed in Pichia pastoris using NAD as substrate pretreated for 30 mins followed by substrate addition measured after 15 to 45 mins
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 471.42, ALogP 3.74, HBA 6, HBD 3, PSA 112.82, QED 0.38
Compound (SMILES): Cc1cnc(C(=O)N[C@@H](CCO)[C@@H](O)CO)cc1Cc1ccc(-n2cccn2)cc1
InChIKey: KBQUSWDCBFPWKE-FPOVZHCZSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Positive allosteric modulation of human muscarinic M1 receptor expressed in CHO cells assessed as increase in ACh-induced intracellular calcium level preincubated for 10 mins followed by ACh addition measured every 2 secs for 80 secs by Fluo-4 dye-based FLIPR assay
Measurement: EC50 > 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 410.47, ALogP 1, HBA 7, HBD 4, PSA 120.5, QED 0.42
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@@H]1CCN(S(C)(=O)=O)C1
InChIKey: ITVPJECOOYHMHF-SECBINFHSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (808-end residues) in presence of ATP
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 295.37, ALogP 0.43, HBA 5, HBD 1, PSA 82.19, QED 0.89
Compound (SMILES): O=C(O)C[C@H](NC(=O)C1CCN(C(=O)Oc2ccccc2)CC1)C(=O)COc1c(F)c(F)cc(F)c1F
InChIKey: ILQUYDVYBHRKFE-KRWDZBQOSA-N
Target: Caspase-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42574
Assay: Inhibition of Anti-Fas antibody-induced caspase-3 activity in human Jurkat E6-1 cells using Ac-DEVD-AMC substrate by fluorescence based assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 526.44, ALogP 3.06, HBA 6, HBD 2, PSA 122.24, QED 0.38
Compound (SMILES): CCOC(=O)c1c(N2CCN(c3ccccc3F)CC2)c2ccccc2n(C)c1=O
InChIKey: SOSVAJWKPJAXAR-UHFFFAOYSA-N
Target: 4,4'-diapophytoene synthase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: A9JQL9
Assay: Inhibition of Staphylococcus aureus dehydrosqualene synthase
Measurement: Ki = 7870 nM (pChEMBL 5.099999904632568)
Descriptors: MW 409.46, ALogP 3.18, HBA 6, HBD 0, PSA 54.78, QED 0.62
Compound (SMILES): COc1cnc(C(=O)Nc2ccc(F)c([C@@]3(C)N=C(N)O[C@H](CF)[C@@H]3F)c2)cn1
InChIKey: QVFZVZFFEJQDAB-QIIPPGSGSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of recombinant human BACE1 (43 to 454 residues) expressed in Escherichia coli BL21(DE3) using Biotin-epsilon-amino-n-capronic acid-SEVNLDAEFRHDSGC-Eu after 3 hrs by HTRF assay
Measurement: IC50 = 17.9 nM (pChEMBL 7.75)
Descriptors: MW 409.37, ALogP 2.11, HBA 7, HBD 2, PSA 111.72, QED 0.78
Compound (SMILES): O=c1ncccn1Cc1ccc(-n2cc(Cn3ccc4nc(-c5ccccc5F)nc-4c3)nn2)cc1
InChIKey: DBUMCDMRQADDBH-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of Hepatitis C virus genotype 1b NS5B RNA-dependent-RNA polymerase assessed as reduction in viral replication after 72 hrs by indirect immunofluorescence assay
Measurement: EC50 = 96.35 nM (pChEMBL 7.019999980926514)
Descriptors: MW 478.49, ALogP 3.42, HBA 9, HBD 0, PSA 96.31, QED 0.36
Compound (SMILES): CC(=O)Nc1ccccc1-c1cccc2c1[nH]c1c(Cl)c(Cl)ccc12
InChIKey: NBOLCRLYNDUVOP-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Displacement of ARTK(Bio)QTARK(Aoa-RADP)S from His6-tagged PARP14 MD2 (A994 to N1191 residues) (unknown origin) expressed in bacterial expression system after 30 mins by AlphaScreen assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 369.25, ALogP 6.25, HBA 1, HBD 2, PSA 44.89, QED 0.43
Compound (SMILES): Cc1nc(N)nc2sc(-c3cnc(Cl)c(NS(=O)(=O)c4ccc(F)cc4)c3)cc12
InChIKey: UBCWTPNRACWDAI-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human N-terminal GST-tagged PI3Kalpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by Kinase-GLo luminescence assay
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 449.92, ALogP 4.24, HBA 7, HBD 2, PSA 110.86, QED 0.45
Compound (SMILES): COc1ccc(/C=C2\C(=O)N(c3cccc(C(=O)O)c3)N=C2C(F)(F)F)cc1Br
InChIKey: PSSZQWNENLGFCY-QPEQYQDCSA-N
Target: LgtC (SINGLE PROTEIN), Neisseria meningitidis
UniProt: Q93EK7
Assay: Inhibition of recombinant Neisseria meningitidis glycosyltransferase LgtC using UDP-Gal/lactose as substrate preincubated for 30 mins with UDP-Gal followed by lactose addition measured after 20 mins in presence of MnCl2 and calf intestinal phosphatase by malachite green dye based enzyme-coupled colorimetric assay relative to control
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 469.21, ALogP 4.5, HBA 4, HBD 1, PSA 79.2, QED 0.67
Compound (SMILES): Cc1ccncc1-c1ccc(-c2cc(C(=O)O)c3ccccc3n2)cc1
InChIKey: WMVIFIIXQKFODX-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of DHODH (unknown origin) expressed in Escherichia coli Rosetta2(DE3) assessed as reduction of DCIP using dihydroorotate as substrate preincubated for 30 mins followed by substrate addition in presence of CoQ10 measured after 1 hr
Measurement: IC50 = 373 nM (pChEMBL 6.429999828338623)
Descriptors: MW 340.38, ALogP 4.97, HBA 3, HBD 1, PSA 63.08, QED 0.57
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCSC)C(C)C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: XBNFGEUHYGBDPE-CNDRSWSLSA-N
Target: Proprotein convertase subtilisin/kexin type 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NBP7
Assay: Inhibition of recombinant human C-terminal His8-tagged PCSK9 expressed in Chinese hamster ovary cells by TR-FRET assay
Measurement: IC50 = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 1902.3
Compound (SMILES): C=C(C)[C@@H]1CC[C@]2(CNCCc3ccccn3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
InChIKey: IPORZYJGANVTDB-KRMOPOIMSA-N
Target: Gag-Pol polyprotein (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)
UniProt: P04585
Assay: Binding affinity to CA-SP1 P373S mutant in HIV-1 subtype B NL4-3 infected in human MT2 cells assessed as inhibition of viral maturation by measuring virus yields after 4 to 5 days in presence of 10% FBS/15 mg/ml HSA by luciferase reporter gene assay
Measurement: EC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 648.98, ALogP 10.26, HBA 3, HBD 2, PSA 62.22, QED 0.22
Compound (SMILES): C=CC(=O)NCCCC[C@H](NC(=O)Cc1ccccc1)C(=O)N1CCN(c2cccc(Cl)n2)CC1
InChIKey: VJKGFDGDSXHIFU-NRFANRHFSA-N
Target: Protein-glutamine gamma-glutamyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P21980
Assay: Inhibition of human TGase 2 using R-I-Cad/DMC as substrate preincubated for 5 mins followed by substrate addition measured at 30 secs interval over 900 secs by fluorescence anisotropy assay
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 498.03, ALogP 2.58, HBA 5, HBD 2, PSA 94.64, QED 0.28
Compound (SMILES): O=C(NO)C1CN(C(=O)c2ccccc2Br)CCN1S(=O)(=O)c1ccccc1
InChIKey: FZBQPTGPOKWUIP-UHFFFAOYSA-N
Target: Falcilysin (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: Q76NL8
Assay: Inhibition of Plasmodium falciparum 3D7 FLN (55 to 1193 residues) expressed in Escherichia coli BL21 using Dabcyl-HKRHSFRMRG-EDANS as substrate preincubated for 5 mins followed by substrate addition measured for 10 mins by fluorescence assay
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 468.33, ALogP 1.47, HBA 5, HBD 2, PSA 107.02, QED 0.52
Compound (SMILES): CCOC(=O)c1c(N2CCN(c3ccccc3F)CC2)c2ccccc2n(CC)c1=O
InChIKey: HIZBHOLMOKPORQ-UHFFFAOYSA-N
Target: 4,4'-diapophytoene synthase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: A9JQL9
Assay: Inhibition of Staphylococcus aureus dehydrosqualene synthase
Measurement: Ki = 8330 nM (pChEMBL 5.079999923706055)
Descriptors: MW 423.49, ALogP 3.66, HBA 6, HBD 0, PSA 54.78, QED 0.59
Compound (SMILES): CCS(=O)(=O)c1ccc(OCCO)c(-c2cn(C)c(=O)c3ccc(-c4cnn(C)c4)cc23)c1
InChIKey: CAISPYQAAZOGNK-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 467.55, ALogP 2.77, HBA 8, HBD 1, PSA 103.42, QED 0.45
Compound (SMILES): O=S(=O)(Nc1ccccc1-c1cccc2c1[nH]c1ccccc12)c1ccccc1
InChIKey: IHJXDLSTMDQLJJ-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Displacement of ARTK(Bio)QTARK(Aoa-RADP)S from His6-tagged PARP14 MD2 (A994 to N1191 residues) (unknown origin) expressed in bacterial expression system after 30 mins by AlphaScreen assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 398.49, ALogP 5.79, HBA 2, HBD 2, PSA 61.96, QED 0.4
Compound (SMILES): CCC[C@H](C(=O)Nc1cccc(-c2cnn(C)c2)c1)N1C/C(=N/N(C)C)NC[C@@H](Cc2cc(Cl)ccc2OC)C1=O
InChIKey: NXHYJWBLLSRBTJ-ATIYNZHBSA-N
Target: Kallikrein-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P49862
Assay: Inhibition of recombinant human KLK7 using MOCAc-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH2 as substrate preincubated for 10 mins followed by substrate addition measured after 30 mins by fluorescence assay
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 580.13, ALogP 4.02, HBA 7, HBD 2, PSA 104.09, QED 0.35
Compound (SMILES): Cc1cnc(Nc2ccc(OCCCOCCCCOCCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCc3ccc(-c4scnc4C)cc3)C(C)(C)C)cc2)nc1NCCCN(C)C(=O)C1CCC1
InChIKey: XCWLFSSUZCTHRG-FHGSKKDFSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Binding affinity to human full length wild-type TBK1 expressed in mammalian expression system
Measurement: Kd = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 1028.33
Compound (SMILES): O/N=C(\Cc1ccccc1)c1nc2cc(Cl)ccc2o1
InChIKey: ZXKOQSKENGIXCM-QGOAFFKASA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P47989
Assay: Inhibition of Xanthine oxidase (unknown origin) using xanthine as substrate preincubated for 1 to 5 mins followed by substrate addition
Measurement: IC50 = 58100 nM (pChEMBL 4.239999771118164)
Descriptors: MW 286.72, ALogP 3.9, HBA 4, HBD 1, PSA 58.62, QED 0.45
Compound (SMILES): CCOC(=O)N1CCN(C(=O)CNC(=O)c2cc(OC)c3ccccc3n2)CC1
InChIKey: NVRXKZUIIZHGKM-UHFFFAOYSA-N
Target: P2Y purinoceptor 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H244
Assay: Displacement of [3H]2MeSADP from P2Y12 receptor in human platelets after 60 mins by TopCount scintillation counting method
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 400.44, ALogP 1.27, HBA 6, HBD 1, PSA 101.07, QED 0.81
Compound (SMILES): O=C(Nc1cccc(-c2ccc(C(F)(F)F)cc2)c1)OCc1ccco1
InChIKey: PZXGURTZSMESRQ-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of recombinant human MAGL using 7-HRA as substrate preincubated for 60 mins followed by substrate addition by fluorescence assay
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 361.32, ALogP 5.71, HBA 3, HBD 1, PSA 51.47, QED 0.65
Compound (SMILES): Cc1cn2c(-c3cn[nH]c3)cnc2c(Nc2cc(Cc3ccncc3)ns2)n1
InChIKey: OUPQYNOPVRTMNB-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using Tamra-PKAtide as substrate by fluorescence polarization assay
Measurement: IC50 < 4 nM (pChEMBL 8.39799976348877)
Descriptors: MW 388.46, ALogP 3.61, HBA 8, HBD 2, PSA 96.68, QED 0.48
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]ncc3c2)C(c2ccc(F)c(CC(=O)NCC3CCN(C4CC4)CC3)c2)NC(=O)N1
InChIKey: RMFZMKRQAGZACL-UHFFFAOYSA-N
Target: G protein-coupled receptor kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P34947
Assay: Assays for Inhibition of GRKs: GRK1, 2 and 5 kinetic assays were conducted in a buffer containing 20 mM HEPES pH 7.0, 5 μM ATP, 2 mM MgCl2, and 0.025% DDM with 50 nM GRK and either 500 nM bROS or 500 nM soluble substrate tubulin in 5 min reactions. The low salt concentration and DDM were used to maximize GRK activity and disrupt small molecule aggregates from forming, respectively. Reactions were quenched with SDS loading buffer, separated via SDS-PAGE, dried and exposed with a phosphorimaging screen prior to quantification via Typhoon imager, as previously reported (see Thal et al., ACS Chemical Biology 7(11):1830-1839 (2012)). Data was analyzed and inhibition curves were fit via GraphPad Prism.
Measurement: IC50 = 11800 nM (pChEMBL 4.929999828338623)
Descriptors: MW 559.65, ALogP 3.5, HBA 5, HBD 5, PSA 131.25, QED 0.29
Compound (SMILES): Cc1nn(-c2ccc(C#N)cc2Cl)c(C)c1Cc1ccc(C(=O)NCCOCCOCCOCCNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](O)[C@H](N)Cc2ccccc2)cc1
InChIKey: ITBLIPSXEWWMSK-QAOPUTECSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Displacement of [17-alpha-methyl-H-3] mibolerone from wild-type androgen receptor (unknown origin) expressed in human Freestyle293F cells measured after 3 hrs
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 830.43, ALogP 3.96, HBA 11, HBD 5, PSA 202.85, QED 0.06
Compound (SMILES): CC(c1ccccc1)N1CCN(c2ncnc3c2nc(-c2ccccc2Cl)n3-c2ccc(Cl)cc2)CC1
InChIKey: YLGZURATVFLYJF-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP55940 from human CB1 expressed in CHOK1 cell membranes
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 529.48, ALogP 6.67, HBA 6, HBD 0, PSA 50.08, QED 0.25
Compound (SMILES): Cc1cnc(Cl)nc1Oc1ccccc1
InChIKey: SIUCVRFPIBGHGC-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13526
Assay: Inhibition of human N-terminal His6-tagged Pin1 PPIase activity expressed in Escherichia coli BL21 using Suc-Ala-Glu-cis-Pro-Phe-4-nitroanilide as substrate preincubated for 10 mins followed by substrate addition monitored for 90 secs by protease enzyme coupled based spectrophotometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 220.66, ALogP 3.23, HBA 3, HBD 0, PSA 35.01, QED 0.73
Compound (SMILES): O=C(/C=C/c1ccccc1Cl)N1CCN(Cc2ccc(O)c3ncccc23)CC1
InChIKey: FQHUSEWLRSMGOD-CSKARUKUSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of HFIP-pretreated amyloid beta (1 to 42) (unknown origin) self-induced aggregation after 48 hrs by thioflavin T-based fluorometric assay
Measurement: IC50 = 7350 nM (pChEMBL 5.130000114440918)
Descriptors: MW 407.9, ALogP 3.95, HBA 4, HBD 1, PSA 56.67, QED 0.67
Compound (SMILES): C[C@@H](O)[C@H](NC(=O)C(C)(C)NC(=O)[C@H](CCCCNC(=O)[C@@H](N)CCCCNC(=O)COCC(=O)NCCCOCCOCCOCCCNC(=O)CC[C@H](NC(=O)[C@H]1CC[C@H](CNC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)CC1)C(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)C(C)(C)NC(=O)[C@H](CC1CCCCC1)NC(=O)[C@H](Cc1ccncc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@H](CO)NC(=O)c1c[nH]cn1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1CCCCC1)C(N)=O
InChIKey: JRKMVKHELMNDHE-HSIUSKJASA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Displacement of [125I]-PYY from human neuropeptide Y2 receptor expressed in CHO cell membranes incubated for 60 mins by TopCount micro scintillation analysis
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 2915.57
Compound (SMILES): CCN(CCCn1sc2cc(OC)c(OC)cc2c1=O)Cc1ccccc1N(C)C
InChIKey: JPZASVYGMGJSDV-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE using acetylthiocholine iodide as substrate measured after 15 mins by Ellman's method
Measurement: IC50 = 9700 nM (pChEMBL 5.010000228881836)
Descriptors: MW 429.59, ALogP 4.06, HBA 7, HBD 0, PSA 46.94, QED 0.49
Compound (SMILES): COc1ccc2cc(-c3c(C)c(-c4cc(Cl)cc(Cl)c4)nn3C(C)c3ccc(C(=O)NCCC(=O)O)cc3)ccc2c1
InChIKey: DIMJDZRCNOLERT-UHFFFAOYSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Antagonist activity at human glucagon receptor expressed in HEK293T cells assessed as inhibition of glucagon-induced cAMP accumulation after 30 mins by HTRF assay
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 602.52, ALogP 7.81, HBA 5, HBD 2, PSA 93.45, QED 0.18
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)CNC(=O)COCCCOCCCCOCCCOc2ccc(Nc3ncc(Br)c(NCCCN(C)C(=O)C4CCC4)n3)cc2)cc1
InChIKey: RHMRGNADRCTXDD-QHIUNZLJSA-N
Target: von Hippel-Lindau disease tumor suppressor/Elongin-C/Elongin-B/HIF1A (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16665
Assay: Inhibition of His-tagged VHL/elongin B/elongin C (unknown origin) interaction with HIF1alpha preincubated for 10 mins followed by fluorescin labelled HIF1alpha peptide addition measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 1037.09
Compound (SMILES): COC(=O)Nc1ccc(-c2cc([C@H](C[C@@H]3CCCN(C(C)=O)C3)NC(=O)/C=C/c3cc(Cl)ccc3-n3cnnn3)nnc2Cl)cc1
InChIKey: QCCGVMDYTWPPFU-MEMBLYCYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of human factor 11a using pyro-Glu-Pro-Arg-pNA as substrate measured after 10 to 120 mins by spectrophotometric method
Measurement: Ki = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 664.55, ALogP 5.12, HBA 10, HBD 2, PSA 157.12, QED 0.23
Compound (SMILES): Nc1nc(N)c2nc(CCCCCc3ccccc3)ccc2n1
InChIKey: JIJJTWFWWPVHEJ-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of recombinant human DHFR using dihydrofolate as substrate after 15 mins in presence of NADPH
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 307.4, ALogP 3.14, HBA 5, HBD 2, PSA 90.71, QED 0.68
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@@H]1CCN(S(=O)(=O)c2ccc(C#N)cc2)C1
InChIKey: TZFYOZLUAPIIJS-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (808-end residues) in presence of ATP
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 382.45, ALogP 1.73, HBA 6, HBD 1, PSA 105.98, QED 0.74
Compound (SMILES): Cc1cccc(-c2c(C)c(-c3cc(Cl)cc(Cl)c3)nn2C(C)c2ccc(C(=O)NCCC(=O)O)cc2)c1
InChIKey: JCWPJMZUYZYKSV-UHFFFAOYSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Antagonist activity at human glucagon receptor expressed in HEK293T cells assessed as inhibition of glucagon-induced cAMP accumulation after 30 mins by HTRF assay
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 536.46, ALogP 6.95, HBA 4, HBD 2, PSA 84.22, QED 0.26
Compound (SMILES): Cc1c(Sc2ccc3ccccc3c2)n(C)c2nc(N)nc(N)c12
InChIKey: HOZSLDLWHVQRPQ-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Pneumocystis jirovecii
UniProt: Q9UUP5
Assay: Inhibition of Pneumocystis jirovecii recombinant DHFR expressed in Escherichia coli Rosetta Gami B (DE3) competent cells using DHFA as substrate and NADPH
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 335.44, ALogP 3.75, HBA 6, HBD 2, PSA 82.75, QED 0.58
Compound (SMILES): Oc1n[nH]c2ccc(Cl)cc12
InChIKey: QENJUGGVVMREAK-UHFFFAOYSA-N
Target: D-amino-acid oxidase (SINGLE PROTEIN), Sus scrofa
UniProt: P00371
Assay: Binding affinity to pig kidney DAAO by ITC method
Measurement: Kd = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 168.58, ALogP 1.92, HBA 2, HBD 2, PSA 48.91, QED 0.63
Compound (SMILES): COc1ccc(Cl)cc1C[C@@H]1CN/C(=N\N(C)C)CN(CC(=O)Nc2cccc(-c3cccs3)c2)C1=O
InChIKey: XHMXKZMERBOWNH-HXUWFJFHSA-N
Target: Kallikrein-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P49862
Assay: Inhibition of recombinant human KLK7 using MOCAc-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH2 as substrate preincubated for 10 mins followed by substrate addition measured after 30 mins by fluorescence assay
Measurement: IC50 = 870 nM (pChEMBL 6.059999942779541)
Descriptors: MW 540.09, ALogP 4.18, HBA 6, HBD 2, PSA 86.27, QED 0.42
Compound (SMILES): COCCOc1cccc(CC2CCN(CCc3ccc4c(c3)C(=O)CCO4)CC2)c1
InChIKey: PTAYGOIFNCZWSM-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Displacement of [3H]-citalopram from human SERT expressed in HEK293 cell membranes after 60 mins by liquid scintillation counting
Measurement: Ki = 202 nM (pChEMBL 6.699999809265137)
Descriptors: MW 423.55, ALogP 4.17, HBA 5, HBD 0, PSA 48, QED 0.57
Compound (SMILES): COC(=O)/C=C(/C)N/C=C/C(=O)c1ccc(NC(=S)Nc2ccc(S(=O)(=O)Nc3ccccn3)cc2)cc1
InChIKey: UTVGAKNCTZPXEV-YDNIAVERSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR-2 after 2.5 hrs by ELISA
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 551.65, ALogP 4.05, HBA 8, HBD 4, PSA 138.52, QED 0.13
Compound (SMILES): COc1ncc(-c2ccc3ncnc(N[C@H]4CCN(C(=O)C5CCOCC5)C4)c3c2)cc1C#N
InChIKey: JLSBWFIGKBSYSZ-FQEVSTJZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3K p110alpha (unknown origin) using lipid substrate after 40 mins by kinase-Glo assay
Measurement: IC50 = 25.6 nM (pChEMBL 7.590000152587891)
Descriptors: MW 458.52, ALogP 3.01, HBA 8, HBD 1, PSA 113.26, QED 0.62
Compound (SMILES): C=C(C)[C@@H]1CC[C@]2(CNCCCN(C)c3ccccc3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
InChIKey: HMQIGXBVNUQDBU-IDGVJNQSSA-N
Target: Gag-Pol polyprotein (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)
UniProt: P04585
Assay: Binding affinity to CA-SP1 P373S mutant in HIV-1 subtype B NL4-3 infected in human MT2 cells assessed as inhibition of viral maturation by measuring virus yields after 4 to 5 days in presence of 10% FBS by luciferase reporter gene assay
Measurement: EC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 691.06, ALogP 11.15, HBA 3, HBD 2, PSA 52.57, QED 0.19
Compound (SMILES): COc1cccc(Sc2c(C)c3c(N)nc(N)nc3n2C(C)C)c1
InChIKey: UMOCMFBMLACMGG-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Pneumocystis jirovecii
UniProt: Q9UUP5
Assay: Inhibition of Pneumocystis jirovecii recombinant DHFR expressed in Escherichia coli Rosetta Gami B (DE3) competent cells using DHFA as substrate and NADPH
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 343.46, ALogP 3.64, HBA 7, HBD 2, PSA 91.98, QED 0.75
Compound (SMILES): Oc1ccccc1-c1csc(-c2ncccn2)n1
InChIKey: PIABKNBHTQXCHG-UHFFFAOYSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase in supersomes (unknown origin) using 7-methoxy-4-trifloromethyl coumarone as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 0.42 nM (pChEMBL 9.380000114440918)
Descriptors: MW 255.3, ALogP 2.97, HBA 5, HBD 1, PSA 58.9, QED 0.76
Compound (SMILES): CC(=O)Nc1cccnc1-c1cccc2c1[nH]c1ccccc12
InChIKey: FQTDIJOYSWGUJT-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Displacement of ARTK(Bio)QTARK(Aoa-RADP)S from His6-tagged PARP14 MD2 (A994 to N1191 residues) (unknown origin) expressed in bacterial expression system after 30 mins by AlphaScreen assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 301.35, ALogP 4.34, HBA 2, HBD 2, PSA 57.78, QED 0.58
Compound (SMILES): CCCOc1ccc(S(C)(=O)=O)cc1-c1cn(C)c(=O)c2ccc(-c3cnn(C)c3)cc12
InChIKey: YEVXDWNUGUUFOG-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): Cc1ccc(NC(=O)c2cc3nc(Nc4c(F)cccc4Cl)n(C)c3c3c2OC(C)(C)C3)c(F)c1
InChIKey: JFWCQGNDSLAGCF-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of recombinant human mPGES1 expressed in CHO cells assessed as reduction in PGE2 production using PGH2 as substrate incubated for 10 mins followed by substrate addition measured for 1 min
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 496.95, ALogP 6.52, HBA 5, HBD 2, PSA 68.18, QED 0.34
Compound (SMILES): Cn1cc(-c2cccc(CNS(C)(=O)=O)c2)c2ccccc2c1=O
InChIKey: BZOKPFNDBIFYQS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged human BRD4-BD1 using H4K5acK8acK12acK16ac as substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by AlphaScreen assay
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 342.42, ALogP 2.25, HBA 4, HBD 1, PSA 68.17, QED 0.79
Compound (SMILES): CCNC(=O)c1cc2c(-c3cc(OCCCCCn4cc(-c5ncnc6[nH]ccc56)cn4)c(Cl)cc3Cl)nc(N)nc2s1
InChIKey: JWGBBMIONSETGN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 using poly[Glu:Tyr] (4:1) as substrate in presence of [gamma33P]-ATP
Measurement: IC50 = 3450 nM (pChEMBL 5.460000038146973)
Descriptors: MW 636.57, ALogP 6.38, HBA 10, HBD 3, PSA 149.52, QED 0.14
Compound (SMILES): COc1ccccc1C(C)NC(=O)c1cc(C2NC(=O)NC(C)=C2C(=O)Nc2ccc3[nH]ncc3c2)ccc1F
InChIKey: UWIYUJKCXJAORH-UHFFFAOYSA-N
Target: Beta-adrenergic receptor kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25098
Assay: Inhibition of GRK2 (unknown origin) preincubated for 10 mins followed by peptide substrate and ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 542.57, ALogP 4.47, HBA 5, HBD 5, PSA 137.24, QED 0.23
Compound (SMILES): O=c1c2c(O)cccc2oc2cc(NS(=O)(=O)c3cccc4ccccc34)c(O)c(O)c12
InChIKey: UIQSDCZBQNDLLV-UHFFFAOYSA-N
Target: Phosphoglycerate mutase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18669
Assay: Inhibition of recombinant PGAM1 (unknown origin) using 3-PG as substrate preincubated for 2 mins followed by substrate addition
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 449.44, ALogP 4.02, HBA 7, HBD 4, PSA 137.07, QED 0.24
Compound (SMILES): CCOc1cc([C@H](c2cc3cc(Br)ccc3cc2OC)[C@@](O)(CCN(C)C)c2cccc3ccoc23)cc(OC)n1
InChIKey: MSJHOUUZBVYELU-ZQWAWDFXSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp assay
Measurement: IC50 = 7500 nM (pChEMBL 5.119999885559082)
Descriptors: MW 619.56, ALogP 7.13, HBA 7, HBD 1, PSA 77.19, QED 0.17
Compound (SMILES): O=[N+]([O-])c1cncnc1Oc1cccc2ocnc12
InChIKey: SCVJWNBTJXUUIZ-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13526
Assay: Inhibition of human N-terminal His6-tagged Pin1 PPIase activity expressed in Escherichia coli BL21 using Suc-Ala-Glu-cis-Pro-Phe-4-nitroanilide as substrate preincubated for 10 mins followed by substrate addition monitored for 90 secs by protease enzyme coupled based spectrophotometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 258.19, ALogP 2.32, HBA 7, HBD 0, PSA 104.18, QED 0.52
Compound (SMILES): FC(F)(F)c1cnc(Cl)nc1Oc1cccc2ocnc12
InChIKey: CVUVZPVEPPAVNL-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13526
Assay: Inhibition of human N-terminal His6-tagged Pin1 PPIase activity expressed in Escherichia coli BL21 using Suc-Ala-Glu-cis-Pro-Phe-4-nitroanilide as substrate preincubated for 10 mins followed by substrate addition monitored for 90 secs by protease enzyme coupled based spectrophotometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 315.64, ALogP 4.08, HBA 5, HBD 0, PSA 61.04, QED 0.67
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCCCCN2CCCCC2)cc1.O=C(O)C(=O)O
InChIKey: XTIRUXCLMQLKTK-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in CHOK1 cell membranes after 90 mins
Measurement: Ki = 325.9 nM (pChEMBL 6.489999771118164)
Descriptors: MW 359.6, ALogP 6.58, HBA 2, HBD 0, PSA 12.47, QED 0.39
Compound (SMILES): CCc1ccc2c(=O)n(C)cc(-c3cccc(NS(C)(=O)=O)c3)c2c1
InChIKey: ZKPRCKAGIJBJRZ-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 356.45, ALogP 3.14, HBA 4, HBD 1, PSA 68.17, QED 0.78
Compound (SMILES): Cc1[nH]c2ccccc2c1C1=C(Cl)C(=O)c2ncccc2C1=O
InChIKey: XUVBFRGQXWRLLK-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Coxsackievirus B3 (strain Nancy)
UniProt: P03313
Assay: Inhibition of human coxsackievirus B3 protease 3C expressed in Escherichia coli (BL21) using fluorogenic-Dabcyl-KEALFQGPPQFE-Edans as substrate after 1 hr by FRET assay
Measurement: IC50 = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 322.75, ALogP 3.9, HBA 3, HBD 1, PSA 62.82, QED 0.74
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]ncc3c2)C(c2ccc(F)c(CCC(=O)NCc3ncc(C)o3)c2)NC(=O)N1
InChIKey: PPSNGNNNGQIFQA-UHFFFAOYSA-N
Target: Beta-adrenergic receptor kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25098
Assay: Inhibition of GRK2 (unknown origin) preincubated for 10 mins followed by peptide substrate and ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 531.55, ALogP 3.51, HBA 6, HBD 5, PSA 154.04, QED 0.23
Compound (SMILES): COC(=O)Nc1ccc(-c2cc([C@H](Cc3ccccc3)NC(=O)/C=C/c3cc(Cl)ccc3-n3cnnn3)c(=O)[nH]n2)cc1
InChIKey: PKBRRVGYZCGPJZ-BULTVDLSSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of human factor 11a using pyro-Glu-Pro-Arg-pNA as substrate measured after 10 to 120 mins by spectrophotometric method
Measurement: Ki = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 597.04, ALogP 4.36, HBA 9, HBD 3, PSA 156.78, QED 0.21
Compound (SMILES): C[C@H](c1ccc(C(F)(F)F)cc1)n1c2c(c3cc(F)cc(S(C)(=O)=O)c31)CCC[C@@H]2CC(=O)O
InChIKey: KSSMIJUMUAANAX-UKRRQHHQSA-N
Target: Prostaglandin D2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q13258
Assay: Antagonist activity at DP1 receptor (unknown origin)
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 497.51, ALogP 5.71, HBA 4, HBD 1, PSA 76.37, QED 0.46
Compound (SMILES): CCCN1CCC(N(CCOC)C(=O)Nc2cccc(C(F)(F)F)c2)CC1
InChIKey: WMXSUWSORZZXFA-UHFFFAOYSA-N
Target: DCN1-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GG9
Assay: Binding affinity biotinylated human GST-tagged DCN1 assessed as inhibition of protein interaction with AlexaFluor 488-tagged and N-terminally acetylated human UBE2M (1 to 12 residues) after 1 hr by TR-FRET assay
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 387.45, ALogP 4.06, HBA 3, HBD 1, PSA 44.81, QED 0.77
Compound (SMILES): CC(C)OC(=O)N1CCC2(CC1)CC(CCCOc1ccc(C(=O)NC3CC3)nc1)C2
InChIKey: DEDOMQJVTCLAJK-UHFFFAOYSA-N
Target: Glucose-dependent insulinotropic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDV5
Assay: Agonist activity at human GPR119 expressed in Flp-In-T-Rex-HEK293 cells assessed as increase in intracellular cAMP level after 30 mins by HTRF assay
Measurement: EC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 429.56, ALogP 4.17, HBA 5, HBD 1, PSA 80.76, QED 0.63
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1ccc(C(=O)N[C@@H](Cc2cccnc2)C(=O)NC2(C#N)CCS(=O)(=O)CC2)s1
InChIKey: LHGCJBNEMCCMCH-INIZCTEOSA-N
Target: Falcipain 2 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q9N6S8
Assay: Inhibition of Plasmodium falciparum falcipain-2
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 580.61, ALogP 2.49, HBA 9, HBD 2, PSA 146.84, QED 0.44
Compound (SMILES): CCCCCCCCCCCCCCC(=O)OCC(=O)NCc1ccc(O)c(OC)c1
InChIKey: XHMGGLZTWGHVMD-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Agonist activity at TRPV1 (unknown origin) expressed in human SH-SY5Y cells assessed as increase in calcium influx after 25 mins by Fluo-4 NW dye-based fluorescence assay
Measurement: EC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 435.61, ALogP 5.65, HBA 5, HBD 2, PSA 84.86, QED 0.23
Compound (SMILES): CCn1c2c(c3cc(NC(=O)CC(C)CC(=O)Nc4ccc(C#N)cc4)ccc31)CCCC2
InChIKey: AZPXWWHSXJPJEE-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat (unknown origin) expressed in human Jurkat cells assessed as inhibition of transcriptional activity after overnight incubation by human IL-17 ROR response element driven-bright-glo luciferase reporter gene assay
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 442.56, ALogP 5.41, HBA 4, HBD 2, PSA 86.92, QED 0.51
Compound (SMILES): CC(C)OC(=O)N1CCC2(CC1)CC(CCCOc1ccc(C(=O)NCC(N)=O)c(F)c1)C2
InChIKey: OEGTTWMTCDOIJE-UHFFFAOYSA-N
Target: Glucose-dependent insulinotropic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDV5
Assay: Agonist activity at human GPR119 expressed in Flp-In-T-Rex-HEK293 cells assessed as increase in intracellular cAMP level after 30 mins by HTRF assay
Measurement: EC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 463.55, ALogP 3.24, HBA 5, HBD 2, PSA 110.96, QED 0.55
Compound (SMILES): COCCn1cc(COc2cccc(Cc3cnc(NC(=O)CSc4nc(C)cc(C)n4)s3)c2)nn1
InChIKey: MAUGCLAAQLDMTD-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of recombinant human GST-tagged Sirt1 (133 to 747 residues) using Z-(Ac)Lys-AMC as substrate measured after 4 hrs by high-throughput fluorescence based assay
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 525.66, ALogP 3.69, HBA 11, HBD 1, PSA 116.94, QED 0.22
Compound (SMILES): CCOc1c2c(c(OCC)c3ccccc13)C(=O)N(c1ccc(CC(=O)O)c(Cl)c1)C2
InChIKey: DLLMWYGEIYBCIH-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Partial agonist activity at human EP4 receptor expressed in HEK293-AEQ17 cells assessed as cAMP accumulation by aequorin luminescence assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 439.9, ALogP 5.08, HBA 4, HBD 1, PSA 76.07, QED 0.56
Compound (SMILES): O=C(Nc1ccc2[nH]ccc2c1)c1cccc(NC(=O)c2ccccn2)c1
InChIKey: KJVHOSMVULKZHY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Mus musculus
UniProt: P28028
Assay: Inhibition of mouse full length GST-tagged BRAF V600E mutant using recombinant human full length N-terminal His-tagged MEK1 as substrate preincubated for 1 hr followed by substrate addition measured after 25 mins by Nu-page gel-based phosphor screen analysis
Measurement: IC50 = 3520 nM (pChEMBL 5.449999809265137)
Descriptors: MW 356.39, ALogP 4.07, HBA 3, HBD 3, PSA 86.88, QED 0.52
Compound (SMILES): Nc1nc(-c2cccc(Br)c2)c(C(=O)c2ccccc2Cl)s1
InChIKey: HOWOEBZOMOQMFH-UHFFFAOYSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assay
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 393.69, ALogP 5.04, HBA 4, HBD 1, PSA 55.98, QED 0.63
Compound (SMILES): CCOC(=O)c1c(N2CCN(C(=O)OC(C)(C)C)CC2)c2ccccc2n(C)c1=O
InChIKey: AQABULNBDKGZLO-UHFFFAOYSA-N
Target: 4,4'-diapophytoene synthase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: A9JQL9
Assay: Inhibition of Staphylococcus aureus dehydrosqualene synthase
Measurement: Ki = 5190 nM (pChEMBL 5.289999961853027)
Descriptors: MW 415.49, ALogP 2.77, HBA 7, HBD 0, PSA 81.08, QED 0.72
Compound (SMILES): FC(F)(F)Oc1ccccc1CN1CCN(c2ncnc3c2nc(-c2ccccc2Cl)n3-c2ccc(Cl)cc2)CC1
InChIKey: RSMGRQDWOUGHPT-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP55940 from human CB1 expressed in CHOK1 cell membranes
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 599.44, ALogP 7.01, HBA 7, HBD 0, PSA 59.31, QED 0.21
Compound (SMILES): CC(C)/C=C/CCCCC(=O)NCc1ccc(O)c(O)c1
InChIKey: BZSMUIBFQYJFOC-FNORWQNLSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Agonist activity at recombinant TRPV1 (unknown origin) expressed in HEK293 cells assessed as induction of calcium flux administered for 1 min followed by compound washout via perfusion for 1 min by FURA-2AM-dye based fluorescence assay
Measurement: EC50 = 4930 nM (pChEMBL 5.309999942779541)
Descriptors: MW 291.39, ALogP 3.49, HBA 3, HBD 3, PSA 69.56, QED 0.39
Compound (SMILES): CNC[C@H](c1ccc2ccccc2c1)[C@H](O)c1ccccc1
InChIKey: RSZGIFQDUIROGN-WOJBJXKFSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding affinity to human SERT expressed in HEK293 cells after 60 mins in presence of [3H]imipramine by liquid scintillation counting
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 291.39, ALogP 3.88, HBA 2, HBD 2, PSA 32.26, QED 0.75