lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H]1CCNC[C@H]1Nc1ncc(C(F)(F)F)c(-c2c[nH]c3ccccc23)n1
InChIKey: YGVSSBPHNLLAHU-MEDUHNTESA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 375.4, ALogP 4.05, HBA 4, HBD 3, PSA 65.63, QED 0.65
Compound (SMILES): CN1C(=O)c2ccccc2N(C)c2cc(N[C@H]3CC[C@H](O)CC3)ncc21
InChIKey: XDCQYSVFUPULSL-HDJSIYSDSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4-BD1 (unknown origin) by TR-FRET assay
Measurement: IC50 = 5990 nM (pChEMBL 5.21999979019165)
Descriptors: MW 352.44, ALogP 3.15, HBA 5, HBD 2, PSA 68.7, QED 0.87
Compound (SMILES): COc1ccc(Cl)cc1-c1nn(C)cc1NC(=O)c1cncc2c[nH]nc12
InChIKey: NBFASNUBTMTAFQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: JAK Enzyme Assay: The activity of the isolated recombinant JAK1 and JAK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr, fluorescently labeled on the N-terminus with 5-carboxyfluorescein) using the Caliper LabChip® technology (Caliper Life Sciences, Hopkinton, Mass.). To determine inhibition constants (Ki), compounds were diluted serially in DMSO and added to 50 μL kinase reactions containing purified enzyme (1.5 nM JAK1, or 0.2 nM JAK2), 100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 1.5 μM peptide substrate, ATP (25 μM), 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 μL of an EDTA containing solution (100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM. After termination of the kinase reaction, the proportion of phosphorylated product was determined as a fraction of total peptide substrate using the Caliper LabChip® 3000 according to the manufacturer's specifications. Ki values were then determined using the Morrison tight binding model.
Measurement: Ki = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 382.81, ALogP 3.27, HBA 6, HBD 2, PSA 97.72, QED 0.56
Compound (SMILES): CCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)C
InChIKey: GGDNNDSXPRCDOY-AGVBWZICSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293 cells co-expressing Rlucll-beta-arrestin2 assessed as induction of beta-arrestin2 recruitment to APJ incubated for 30 mins by BRET assay
Measurement: EC50 = 149 nM (pChEMBL 6.829999923706055)
Descriptors: MW 1178.45
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(C#Cc4ccc(F)s4)nc31)[C@H](O)[C@@H]2O
InChIKey: NHRLDLXSIQAXQX-AQPYCOETSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I]AB-MECA from mouse adrenergic A3 receptor expressed in HEK293 cell membranes assessed as inhibitor constant by radio ligand binding assay
Measurement: Ki = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 442.48, ALogP 0.5, HBA 9, HBD 4, PSA 125.19, QED 0.44
Compound (SMILES): Cn1cc(-c2cc(C(C)(C)O)ccc2Oc2ccc(F)cc2F)c2cc(C(=O)NCc3ccc(C(=O)NO)cc3)[nH]c2c1=O
InChIKey: XTZPTYMYXVFWJT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 12.4 nM (pChEMBL 7.909999847412109)
Descriptors: MW 602.59, ALogP 4.88, HBA 7, HBD 5, PSA 145.68, QED 0.13
Compound (SMILES): CCN(c1ccc(C(=O)O)cn1)c1cc(OCC(C)C)c(C(C)C)cc1NC(=O)c1cc2cc3c4c(c2oc1=O)CCCN4CCC3
InChIKey: ULMIFUYGJNTQBU-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Binding affinity to human RXRalpha-LBD assessed as binding constant from binding ratio at 488 nm by fluorometric titration assay
Measurement: Kd <= 1000 nM (pChEMBL 6)
Descriptors: MW 638.76, ALogP 7.15, HBA 8, HBD 2, PSA 125.21, QED 0.17
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CO)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: IZZFNAUKHJUKPH-MTOWIIDVSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 3.56 nM (pChEMBL 8.449999809265137)
Descriptors: MW 404.46, ALogP 0.23, HBA 7, HBD 4, PSA 111.49, QED 0.55
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(F)cc4n3)C2)cc1
InChIKey: AJSYOLPHCHQLPB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): C=CC(=O)N[C@H]1COC[C@H]1Nc1ncc2cc(-c3c(C)c(OC)cc(OC)c3C)c(=O)n(C)c2n1
InChIKey: XMTUBCFDOXDZIL-ZWKOTPCHSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) expressed in human Huh7 cells assessed as autophosphorylation after 1 hr incubation measured by Mesoscale discovery (MSD) assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 479.54, ALogP 2.11, HBA 9, HBD 2, PSA 116.6, QED 0.5
Compound (SMILES): NS(=O)(=O)c1cccc(-c2nnc(-c3ccc([N+](=O)[O-])cc3)o2)c1
InChIKey: YCCFQVBZMCOUJN-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Inhibition of recombinant human carbonic anhydrase 13 by stopped flow CO2 hydrase assay
Measurement: Ki = 16.2 nM (pChEMBL 7.789999961853027)
Descriptors: MW 346.32, ALogP 1.96, HBA 7, HBD 1, PSA 142.22, QED 0.56
Compound (SMILES): CCN1CC2(CCN(CCc3ccc(F)cc3)CC2)O[C@H](C)C1=O
InChIKey: FCUAEDWJSLQAOZ-OAHLLOKOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHOK1 cell membranes incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 164 nM (pChEMBL 6.789999961853027)
Descriptors: MW 334.44, ALogP 2.47, HBA 3, HBD 0, PSA 32.78, QED 0.85
Compound (SMILES): CCNc1nc(N)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(C(=O)NC)C[C@H]12
InChIKey: QGBOEQAEAMHLLV-RFXZSQAESA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 347.38, ALogP -1.13, HBA 9, HBD 5, PSA 151.21, QED 0.47
Compound (SMILES): CN1CCN(C(=O)c2ccc3nc(Nc4ccc(-c5nc(N6CCOCC6)nc(N6CCOCC6)n5)cc4)[nH]c3c2)CC1
InChIKey: WHMJTYCPNSWDLA-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate measured after 1 hr in presence of ATP by ADP-Glo reagent based assay
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 584.69, ALogP 2.22, HBA 11, HBD 2, PSA 127.87, QED 0.35
Compound (SMILES): O=C(Nc1ccc([N+](=O)[O-])cc1)C(c1ccc([N+](=O)[O-])cc1)N(C(=O)c1ccc(C(F)(F)F)cc1)c1ccccc1
InChIKey: GDBNAEMVDGQOCE-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of MMP-13 (unknown origin) by colorimetric assay
Measurement: IC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 564.48, ALogP 6.55, HBA 6, HBD 1, PSA 135.69, QED 0.19
Compound (SMILES): Fc1cnc2[nH]cc(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c2c1
InChIKey: FFOLBBUXUFLVCD-JTQLQIEISA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 380.35, ALogP 3.34, HBA 5, HBD 3, PSA 78.52, QED 0.61
Compound (SMILES): Cc1c(-c2nn(-c3ccccc3)cc2/C=N/O)nnn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: RHZYCASJFPXTCW-SRZZPIQSSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 7710 nM (pChEMBL 5.110000133514404)
Descriptors: MW 423.46, ALogP 1.88, HBA 9, HBD 2, PSA 141.28, QED 0.29
Compound (SMILES): CCOC(=O)N1C[C@@H](c2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2)[C@@](C)(c2ccccc2)C1
InChIKey: XYHMSZPCIZCSPX-AZUAARDMSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 = 599 nM (pChEMBL 6.21999979019165)
Descriptors: MW 475.43, ALogP 5.51, HBA 3, HBD 1, PSA 49.77, QED 0.59
Compound (SMILES): C=CCN1CCN(Cc2cc3nc(-n4c(CC)nc5ccccc54)nc(N4CCOCC4)c3s2)C(=O)C1
InChIKey: BVRGIASICSCQCP-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin)
Measurement: IC50 = 266 nM (pChEMBL 6.579999923706055)
Descriptors: MW 517.66, ALogP 3.26, HBA 9, HBD 0, PSA 79.62, QED 0.35
Compound (SMILES): OCC1CCCN(C2Cc3ccccc3C2)C1
InChIKey: RAZZBNCWCCMMGG-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 231.34, ALogP 1.86, HBA 2, HBD 1, PSA 23.47, QED 0.84
Compound (SMILES): O=C(NO)c1ccc(NC(=O)c2ccc(N3CCOCC3)cc2)cc1
InChIKey: ZOKVYGTWMFWXDJ-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 341.37, ALogP 1.89, HBA 5, HBD 3, PSA 90.9, QED 0.58
Compound (SMILES): N#Cc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1C#N
InChIKey: DUGSEWFNPLJUEV-LBPRGKRZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 411.39, ALogP 3.55, HBA 6, HBD 3, PSA 113.21, QED 0.61
Compound (SMILES): O=C(Nc1ccccc1)OCC1CCCN(Cc2ccccc2)C1
InChIKey: VPDRCWOTGBLGTG-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 324.42, ALogP 4.15, HBA 3, HBD 1, PSA 41.57, QED 0.9
Compound (SMILES): COc1cc(OCc2ccnc(N)n2)cc2sc(N[C@@H]3CCCC[C@H]3O)nc12
InChIKey: QPANAVQRQRUDJJ-ZIAGYGMSSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Binding affinity to c-Kit (unknown origin) by kinome scan assay
Measurement: Kd = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 401.49, ALogP 2.97, HBA 9, HBD 3, PSA 115.41, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cn1
InChIKey: LRKRQTMUHJKJQW-MRXNPFEDSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of CDK2/cyclin A2 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins under thiol free condition by microplate scintillation counter
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 388.43, ALogP 2.48, HBA 6, HBD 2, PSA 100.11, QED 0.65
Compound (SMILES): O=c1[nH]nc(-c2ccc(Cl)c(C(F)(F)F)c2)o1
InChIKey: SBBOPUCCCOEMDA-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 264.59, ALogP 2.7, HBA 3, HBD 1, PSA 58.89, QED 0.86
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2cc(F)ccc2n1
InChIKey: AGMGRCAUAZCHPG-UHFFFAOYSA-N
Target: Activin receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: P36896
Assay: Inhibition of human ALK4 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 568.7 nM (pChEMBL 6.25)
Descriptors: MW 437.52, ALogP 5.07, HBA 5, HBD 1, PSA 45.46, QED 0.43
Compound (SMILES): O=C(Nc1c[nH]nc1-c1cc(Cl)ccc1OC(F)F)c1snc2cccnc12
InChIKey: YENWSVAZJLPGKK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: JAK Enzyme Assay: The activity of the isolated recombinant JAK1 and JAK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr, fluorescently labeled on the N-terminus with 5-carboxyfluorescein) using the Caliper LabChip® technology (Caliper Life Sciences, Hopkinton, Mass.). To determine inhibition constants (Ki), compounds were diluted serially in DMSO and added to 50 μL kinase reactions containing purified enzyme (1.5 nM JAK1, or 0.2 nM JAK2), 100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 1.5 μM peptide substrate, ATP (25 μM), 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 μL of an EDTA containing solution (100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM. After termination of the kinase reaction, the proportion of phosphorylated product was determined as a fraction of total peptide substrate using the Caliper LabChip® 3000 according to the manufacturer's specifications. Ki values were then determined using the Morrison tight binding model.
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 421.82, ALogP 4.59, HBA 6, HBD 2, PSA 92.79, QED 0.49
Compound (SMILES): C[C@@H]1CN(c2ccc(S(C)(=O)=O)cc2)CCN1c1nccc(C(=O)NC2C3CC4CC2CC(O)(C4)C3)n1
InChIKey: FEGJQPCXQMHGGC-JPAYEOGSSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in pooled human liver microsomes using mephenytoin as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.68, ALogP 2.26, HBA 8, HBD 2, PSA 115.73, QED 0.61
Compound (SMILES): C[C@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: STWVLEKJQQRGMO-GUYCJALGSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D7Q1
Assay: Inhibition of recombinant full-length C-terminal his-tagged mouse CHIT1 expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N"-triacetylchitotrioside as substrate after 60 mins by fluorometric assay
Measurement: Ki = 26.05 nM (pChEMBL 7.579999923706055)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.83
Compound (SMILES): Cc1nnc(-c2ccc3cnc(NC(=O)c4ccnc(N(C)C5CCN(C)CC5)c4)cc3c2)s1
InChIKey: ARQUTMKPMAEVSS-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: GSK3 beta kinase assay: Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))].
Measurement: EC50 = 1164 nM (pChEMBL 5.929999828338623)
Descriptors: MW 473.61, ALogP 4.24, HBA 8, HBD 1, PSA 87.14, QED 0.46
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2nc(C#N)ccc12
InChIKey: IPIWQVGRFNIMQX-AWEZNQCLSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 347.43, ALogP 2.62, HBA 6, HBD 3, PSA 102.31, QED 0.67
Compound (SMILES): COC(=O)NS(=O)(=O)c1sc(CC(C)C)cc1-c1cccc(C(=O)Cn2ccnc2C(C)(C)C)c1
InChIKey: SPDXVIKELDWSMA-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using bufuralol as substrate preincubated for 3 mins followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 517.67, ALogP 5.04, HBA 8, HBD 1, PSA 107.36, QED 0.42
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(-c3ccc(Cl)cc3)c3c(N/N=C/c4ccccc4)ncnc32)cc1
InChIKey: AYKMIZNOPIHXLV-AMVVHIIESA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 125.7 nM (pChEMBL 6.900000095367432)
Descriptors: MW 502.99, ALogP 4.83, HBA 7, HBD 2, PSA 115.26, QED 0.25
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2ccc(F)cc2)nc1C#N
InChIKey: KTUYYMOKNXBOLX-PKTZIBPZSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 493.63, ALogP 4.91, HBA 5, HBD 2, PSA 101.88, QED 0.43
Compound (SMILES): Cc1ccc2[nH]cc(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c2c1
InChIKey: XWOQCKJZIGPMAB-LBPRGKRZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 341.85, ALogP 3.75, HBA 4, HBD 3, PSA 65.63, QED 0.68
Compound (SMILES): Cc1cc2cc(NS(=O)(=O)Cc3ccc(C(=O)NO)cc3)ccc2n(C)c1=O
InChIKey: KMSCXGNJNWHVIP-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to BRPF1 (unknown origin) by Isothermal titration calorimetry
Measurement: Kd = 1497 nM (pChEMBL 5.829999923706055)
Descriptors: MW 401.44, ALogP 1.91, HBA 6, HBD 3, PSA 117.5, QED 0.45
Compound (SMILES): Nc1nccc(COc2ccc3nc(NC4CCCCC4)sc3c2)c1Cl
InChIKey: ZXYVWKYLUPYZGL-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Binding affinity to c-Kit (unknown origin) by kinome scan assay
Measurement: Kd = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 388.92, ALogP 5.25, HBA 6, HBD 2, PSA 73.06, QED 0.62
Compound (SMILES): CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2sc(CN3CCN(C(=O)C4CC4)CC3=O)cc2n1
InChIKey: IBRQBMCIRRKONR-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin)
Measurement: IC50 = 185 nM (pChEMBL 6.730000019073486)
Descriptors: MW 545.67, ALogP 3.01, HBA 9, HBD 0, PSA 96.69, QED 0.37
Compound (SMILES): Cc1noc([C@H]2CC[C@H](Nc3ncc(C(F)(F)F)c(-c4c[nH]c5cc(C#N)ccc45)n3)CN2)n1
InChIKey: BUUPGVFPOSYWOV-SUMWQHHRSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 468.44, ALogP 4.11, HBA 8, HBD 3, PSA 128.34, QED 0.41
Compound (SMILES): COc1ccc(-c2ccc3c(NC(=O)CCCCCCC(=O)NO)n[nH]c3c2)cc1
InChIKey: OQKZYTUPMGUCDP-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human C-terminal His/FLAG-tagged HDAC1 (1 to end residues) expressed in sf9 insect cells using Boc-Lys(Ac)-AMC as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 410.47, ALogP 4.02, HBA 5, HBD 4, PSA 116.34, QED 0.23
Compound (SMILES): CNC(=O)[C@@H]1CNC[C@@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: QWTLJZSIFBCFBX-RYUDHWBXSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 418.42, ALogP 2.78, HBA 5, HBD 4, PSA 94.73, QED 0.52
Compound (SMILES): CN1C(=O)c2cccc(Cl)c2Oc2cc(N[C@H]3CC[C@H](O)CC3)ncc21
InChIKey: PJKFSPULHWZLFO-HAQNSBGRSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG stably expressed in CHO cells at holding potential of -80 mV incubated for 12 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 373.84, ALogP 3.83, HBA 5, HBD 2, PSA 74.69, QED 0.84
Compound (SMILES): C[C@H]1OC2(CCN(CCc3ccccc3)CC2)CN(C2CC2)C1=O
InChIKey: BZPKTOXVMUIFBK-MRXNPFEDSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHOK1 cell membranes incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 328.46, ALogP 2.47, HBA 3, HBD 0, PSA 32.78, QED 0.85
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnc4n3CCCC4)c(Cl)cn2)C1
InChIKey: XPZMRZUXNMEPOS-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (ATP Concentration at Km): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (3 nM CDK9/CycT1, 6 μM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 415.93, ALogP 3.57, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): CO[C@@]12CC[C@H](N[C@H](C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)O)C(C)C)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: QLMICPWFXLJOEI-AANUSGNESA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 0.89 nM (pChEMBL 9.050000190734863)
Descriptors: MW 579.69, ALogP 2.33, HBA 8, HBD 5, PSA 140.59, QED 0.3
Compound (SMILES): O=C(CCN1CCCc2ccccc21)Nc1ccccc1
InChIKey: OPDYSVLVMGRCCI-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 263.03 nM (pChEMBL 6.579999923706055)
Descriptors: MW 280.37, ALogP 3.47, HBA 2, HBD 1, PSA 32.34, QED 0.93
Compound (SMILES): CNc1ccc(-c2c3c(nn2C(C)C)CCNCC3)cc1
InChIKey: CWJKEVLEUPKOLX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Displacement of [3H]-CT from rat 5-HT7 receptor expressed in HEK293 cells by competitive radioligand binding assay
Measurement: Ki = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 284.41, ALogP 2.86, HBA 4, HBD 2, PSA 41.88, QED 0.91
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NC12CCC(C(=O)O)(CC1)CC2
InChIKey: QZWSDSOAZQAJDD-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate incubated for 15 mins in presence of NADPH generating system by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 493.4, ALogP 5.88, HBA 3, HBD 2, PSA 79.29, QED 0.48
Compound (SMILES): CC1(CN)CCN(c2cnc(Sc3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: HFZSVNQUAOVFHI-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of wild-type human SHP2 (1 to 535 residues) using DiFMUP and 2p-IRS1 peptide as substrates preincubated for 1 hr and followed by substrate addition and measured by microplate reader method
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 398.36, ALogP 4.08, HBA 6, HBD 2, PSA 81.06, QED 0.81
Compound (SMILES): CCn1c(C(N)=O)cc2c1-c1ccncc1OC21CCC1
InChIKey: HIFKRZORZOSOFC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Haspin Kinase Assay: The kinase assay relies on ADP-GloKM biochemical kinase assay (Promega). This is a luminescent kinase assay that measures ADP formed from a kinase reaction. Then ADP is converted into ATP, which is transformed into a light signal by Ultra-Glo Luciferase. The luminescent signal positively correlates with kinase activity. The assay measures the intrinsic ATPase activity (in the absence of peptidic substrate as phosphate acceptor).The enzyme was purchase from Invitrogen (PV5708) as the kinase domain of GST tagged recombinant human proteins.Assay conditions were as indicated by the kit manufacturers with the following adaptations:Assay buffer: 15 mM HEPES pH 7.4, 20 mM NaCl, 1 mM EGTA, 0.02% Tween 20, 10 mM MgCl2, 0.1 mg/ml BGGAssay volume: 20 μlIncubation time and temperature: 60 min at 30° C.Haspin concentration: 20 nMATP concentration: 150 μMTested compound: Serial 1:3 dilutionsFinal DMSO concentration in the assay: 1%Assays were performed in 384-well plates. The final read out was generated using an EnVision plate reader (Perkin-Elmer). Luminescent relative units are normalized against the control activity included for each compound (i.e., 100% Haspin activity, without compound) and the percentage of inhibition is calculated.
Measurement: IC50 = 26.2 nM (pChEMBL 7.579999923706055)
Descriptors: MW 283.33, ALogP 2.44, HBA 4, HBD 1, PSA 70.14, QED 0.92
Compound (SMILES): Cc1cc(-c2ccc3[nH]nc(C(=O)Nc4ccc(OC5CCN(C)CC5)cc4)c3c2)sn1
InChIKey: IYVIYYUPMDMHRV-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 447.56, ALogP 4.72, HBA 6, HBD 2, PSA 83.14, QED 0.46
Compound (SMILES): CON(C)C(=O)Oc1ccc(-c2cc(=O)c3c(O)cc(OC(=O)N(C)OC)cc3o2)cc1
InChIKey: MAYVYUJUNJKXFY-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE using acetylthiocholine iodide as substrate measured after 15 mins by Ellman's method
Measurement: IC50 = 22600 nM (pChEMBL 4.650000095367432)
Descriptors: MW 444.4, ALogP 3.15, HBA 9, HBD 1, PSA 127.98, QED 0.59
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)CNCCNc3c4c(nc5ccccc35)CCCC4)c2)nc1OCC1CC1
InChIKey: MYLYCZDLVLCRLU-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 1 min followed by substrate addition and measured after 10 mins by Ellman's method
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 585.73, ALogP 4.42, HBA 9, HBD 4, PSA 130.16, QED 0.18
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(C(=O)NCCNC(=O)CCc4cn(CCCCC5CCN(CC(=O)N6c7ccccc7NC(=O)c7ccccc76)CC5)cn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: OTWPYWJMLIDHOJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M4 expressed in CHO-K9 cell membranes measured after 3 hrs by radioligand competition binding assay
Measurement: Ki = 3.715 nM (pChEMBL 8.430000305175781)
Descriptors: MW 984.17, ALogP 6.15, HBA 11, HBD 3, PSA 188.19, QED 0.05
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccc(NC(=O)CCCCCCCCC(=O)NO)cc3C2)c(O)cc1O
InChIKey: HBNSYDADLFRPNT-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using RHK-K(Ac)-AMC as substrate by fluorescence based assay
Measurement: IC50 = 432 nM (pChEMBL 6.369999885559082)
Descriptors: MW 511.62, ALogP 4.94, HBA 6, HBD 5, PSA 139.2, QED 0.16
Compound (SMILES): CC1(C)OC(=O)c2ccc(Nc3ncc(-c4nc(-c5ccncc5)no4)c(N[C@H](CO)c4ccccc4)n3)cc21
InChIKey: AIFRAZQXNNPZBV-HSZRJFAPSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 in anti-CD3/anti-CD28-stimulated human T-cells assessed as inhibition of SLP76 phosphorylation preincubated for 1 hr followed by anti-CD3/CD28 stimulation for 30 mins by AlphaLISA assay
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 535.56, ALogP 4.88, HBA 11, HBD 3, PSA 148.18, QED 0.23
Compound (SMILES): COc1ccccc1-c1c(C(N)=O)[nH]c2c1C(C)(C)Oc1cnccc1-2
InChIKey: RQFFUGYUAUCWSO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Haspin Kinase Assay: The kinase assay relies on ADP-GloKM biochemical kinase assay (Promega). This is a luminescent kinase assay that measures ADP formed from a kinase reaction. Then ADP is converted into ATP, which is transformed into a light signal by Ultra-Glo Luciferase. The luminescent signal positively correlates with kinase activity. The assay measures the intrinsic ATPase activity (in the absence of peptidic substrate as phosphate acceptor).The enzyme was purchase from Invitrogen (PV5708) as the kinase domain of GST tagged recombinant human proteins.Assay conditions were as indicated by the kit manufacturers with the following adaptations:Assay buffer: 15 mM HEPES pH 7.4, 20 mM NaCl, 1 mM EGTA, 0.02% Tween 20, 10 mM MgCl2, 0.1 mg/ml BGGAssay volume: 20 μlIncubation time and temperature: 60 min at 30° C.Haspin concentration: 20 nMATP concentration: 150 μMTested compound: Serial 1:3 dilutionsFinal DMSO concentration in the assay: 1%Assays were performed in 384-well plates. The final read out was generated using an EnVision plate reader (Perkin-Elmer). Luminescent relative units are normalized against the control activity included for each compound (i.e., 100% Haspin activity, without compound) and the percentage of inhibition is calculated.
Measurement: IC50 = 3960 nM (pChEMBL 5.400000095367432)
Descriptors: MW 349.39, ALogP 3.48, HBA 4, HBD 2, PSA 90.23, QED 0.76
Compound (SMILES): Nc1ccc(Nc2ncc(C(F)(F)F)c(NC3CC3)n2)cc1
InChIKey: XWPNWIGEIJKOEC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IYT8
Assay: Inhibition of ULK2 (unknown origin) expressed in HEK293T cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 1687 nM (pChEMBL 5.769999980926514)
Descriptors: MW 309.3, ALogP 3.4, HBA 5, HBD 3, PSA 75.86, QED 0.75
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ncc(NC3CN(CCCF)C3)cc2F)N1CC(F)(F)F
InChIKey: HHXTYKXNOKWJQP-FATZIPQQSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: MCF-7 ER Down-Regulation Assay: The ability of compounds to down-regulate Estrogen Receptor (ER) numbers was assessed in a cell based immuno-fluorescence assay using the MCF-7 human ductal carcinoma breast cell line. MCF-7 cells were revived directly from a cryovial (approx 5×106 cells) in Assay Medium (phenol red free Dulbecco's Modified Eagle's medium (DMEM); Sigma D5921) containing 2 mM L-Glutamine and 5% (v/v) Charcoal/Dextran treated foetal calf serum. Cells were syringed once using a sterile 18G×1.5 inch (1.2×40 mm) broad gauge needle and cell density was measured using a Coulter Counter (Beckman). Cells were further diluted in Assay Medium to a density of 3.75×104 cells per mL and 40 μL per well added to transparent bottomed, black, tissue culture-treated 384 well plates (Costar, No. 3712) using a Thermo Scientific Matrix WellMate or Thermo Multidrop. Following cell seeding, plates were incubated overnight at 37° C., 5% CO2 (Liconic carousel incubator). Test data was generated using the LabCyte Echo model 555 compound reformatter which is part of an automated workcell (Integrated Echo 2 workcell). Compound stock solutions (10 mM) of the test compounds were used to generate a 384 well compound dosing plate (Labcyte P-05525-CV1). 40 μL of each of the 10 mM compound stock solutions was dispensed into the first quadrant well and then 1:100 step-wise serial dilutions in DMSO were performed using a Hydra II (MATRIX UK) liquid handling unit to give 40 μL of diluted compound into quadrant wells 2 (0.1 mM), 3 (1 μM) and 4 (0.01 μM), respectively. 40 μL of DMSO added to wells in row P on the source plate allowed for DMSO normalisation across the dose range. To dose the control wells 40 μL of DMSO was added to row O1 and 40 μL of 100 μM fulvestrant in DMSO was added to row O3 on the compound source plate.
Measurement: IC50 = 0.28 nM (pChEMBL 9.550000190734863)
Descriptors: MW 494.51, ALogP 4.45, HBA 5, HBD 2, PSA 60.08, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2c(F)c(F)c(F)c(F)c2F)cc1
InChIKey: ZSYKTLDQSMAEFY-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 331.1 nM (pChEMBL 6.480000019073486)
Descriptors: MW 488.42, ALogP 1.59, HBA 5, HBD 4, PSA 147.46, QED 0.27
Compound (SMILES): C#CCN1CCCC(OC(=O)N(C)CC)C1
InChIKey: VOYPIHUBPQHSHA-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 224.3, ALogP 1.17, HBA 3, HBD 0, PSA 32.78, QED 0.67
Compound (SMILES): Cc1cc(C)cc(N2C=Nc3cc(Cl)c(-c4cccc(O)c4)cc3C2C(=O)N(C)C[C@H](C)N)c1
InChIKey: JEZABFIGBDYTFL-MDYZWHIJSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 = 960 nM (pChEMBL 6.019999980926514)
Descriptors: MW 477.01, ALogP 5.36, HBA 5, HBD 2, PSA 82.16, QED 0.52
Compound (SMILES): Cc1ccc(C(=O)/C=C/C(=O)N2CCc3ccc(Nc4ncc(C)c(-c5cnn(C(C)C)c5)n4)cc3C2)cc1
InChIKey: WQBKMBBBWFAMFH-VAWYXSNFSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 (866 to end residues) using GEEPLYWSFPAKKK as substrate after 40 mins by [gamma-33ATP] radiometric assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 520.64, ALogP 5.61, HBA 7, HBD 1, PSA 93.01, QED 0.25
Compound (SMILES): N#Cc1ccc(Nc2nccc([C@H](O)c3ccc(-c4ccc(C#N)cc4)cc3C(F)(F)F)n2)cc1
InChIKey: YGDJSUJAJDJUHW-XMMPIXPASA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase Y188L mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 > 24138.8 nM (pChEMBL 4.617000102996826)
Descriptors: MW 471.44, ALogP 5.73, HBA 6, HBD 2, PSA 105.62, QED 0.39
Compound (SMILES): CCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)O)C(C)C)C(C)(C)C
InChIKey: OJHRHYNROJEZIH-CLSZPEQESA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293 cells co-expressing Rlucll-beta-arrestin2 assessed as induction of beta-arrestin2 recruitment to APJ incubated for 30 mins by BRET assay
Measurement: EC50 = 401 nM (pChEMBL 6.400000095367432)
Descriptors: MW 1162.4
Compound (SMILES): CC(C)c1ccc(NC(=O)OC2CCCN(C3Cc4ccccc4C3)C2)cc1
InChIKey: DOQSUJLBOVDRML-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 378.52, ALogP 4.99, HBA 3, HBD 1, PSA 41.57, QED 0.81
Compound (SMILES): C[C@@H](O)[C@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1csc2ccccc12)NC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@H](CS)NC(=O)COCCOCCNC(=S)Nc1ccc2c(c1)C(=O)OC21c2ccc(O)cc2Oc2cc(O)ccc21)C(C)(C)S)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)O)C(C)(C)C
InChIKey: YYGGNPIDYSEJHB-BYEIRUMPSA-N
Target: Na(+)/H(+) exchange regulatory cofactor NHE-RF2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15599
Assay: Binding affinity to NHERF2 PDZ2 domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr by fluorescence polarization based competition assay
Measurement: Kd = 7660 nM (pChEMBL 5.119999885559082)
Descriptors: MW 2123.55
Compound (SMILES): Nc1ccccc1NC(=O)CCCCCNC(=O)/C(Cc1ccc(O)c(Br)c1)=N/O
InChIKey: WGUPMRJFAZHVKS-NLRVBDNBSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant full length C-terminal FLAG/His-tagged human HDAC1 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 477.36, ALogP 3.42, HBA 6, HBD 5, PSA 137.04, QED 0.12
Compound (SMILES): CCOc1ccc2c(c1[C@@H]1C[C@H]1CN)CCO2.Cl
InChIKey: CZVVNGCGYYHXBE-QLSWKGBWSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 781 nM (pChEMBL 6.110000133514404)
Descriptors: MW 233.31, ALogP 2.08, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): CCC(=O)N(CCN1CCC(Cc2ccc(F)cc2)CC1)c1ccc(OC)cc1
InChIKey: QJJOFHXMRIILNX-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHO-K1 cell membranes incubated for 90 mins measured by MicroBeta scintillation counter method
Measurement: Ki = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 398.52, ALogP 4.53, HBA 3, HBD 0, PSA 32.78, QED 0.65
Compound (SMILES): O=c1c2ccc(Cl)cc2oc2ccc(OCCCCCN3CCCCCC3)cc12
InChIKey: LKXYCZQRBHVDER-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI cells using p-tyramine as substrate by fluorometric assay
Measurement: IC50 = 2111 nM (pChEMBL 5.679999828338623)
Descriptors: MW 413.95, ALogP 6.02, HBA 4, HBD 0, PSA 42.68, QED 0.35
Compound (SMILES): CC#CC(=O)Nc1cc2cc(-c3cnn(C)c3)ccc2cn1
InChIKey: VDHIIIYZVNENLN-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. response variable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 513 nM (pChEMBL 6.289999961853027)
Descriptors: MW 290.33, ALogP 2.6, HBA 4, HBD 1, PSA 59.81, QED 0.74
Compound (SMILES): N#Cc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3OC(F)F)c[nH]c2c1
InChIKey: FTHWYCLTONRIMR-LBPRGKRZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 384.39, ALogP 3.26, HBA 6, HBD 3, PSA 98.65, QED 0.62
Compound (SMILES): CC[C@H]1CC[C@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)CN1
InChIKey: SUQQDRCRQDKHCI-STQMWFEESA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 389.43, ALogP 4.59, HBA 4, HBD 3, PSA 65.63, QED 0.61
Compound (SMILES): c1ccc(Cc2ccc(-c3coc4ccc(-c5cn[nH]c5)nc34)cc2)cc1
InChIKey: JOZUGIHTSIWTIK-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of human recombinant CLK4 using YRRAAVPPSPSLS substrate by radiometric scintillation assay
Measurement: IC50 = 355 nM (pChEMBL 6.449999809265137)
Descriptors: MW 351.41, ALogP 5.48, HBA 3, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): Nc1n[nH]c(N2CCC(N3C[C@H](CO)OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: NFCCGJZRWCEETB-DLBZAZTESA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Mus musculus
UniProt: Q91XA9
Assay: Inhibition of full-length C-terminal his-tagged mouse AMCase expressed in expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N'-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 406.92, ALogP 1.31, HBA 7, HBD 3, PSA 103.53, QED 0.69
Compound (SMILES): COc1cc(Nc2nc(N)nc3c2ncn3Cc2ccc(C(=O)Nc3ccccc3N)cc2)cc(OC)c1
InChIKey: BZGXWZHACIVINX-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in baculovirus using fluorogenic peptide p53 residues 379-382 (RHKK(Ac)AMC) as substrate by Fluorescence analysis
Measurement: IC50 = 9610 nM (pChEMBL 5.019999980926514)
Descriptors: MW 510.56, ALogP 4.05, HBA 10, HBD 4, PSA 155.23, QED 0.23
Compound (SMILES): NS(=O)(=O)c1ccc(CCN(Cc2ccc(Cl)cc2)C(=O)Cn2cc(F)c(=O)[nH]c2=O)cc1
InChIKey: HHCRCIWZXNRZMQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human CA1 pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 2965 nM (pChEMBL 5.53000020980835)
Descriptors: MW 494.93, ALogP 1.25, HBA 6, HBD 2, PSA 135.33, QED 0.49
Compound (SMILES): CCOC(=O)CNc1ccc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1
InChIKey: ZMVUYNQVYVTCAD-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 404.43, ALogP 2.1, HBA 9, HBD 2, PSA 116.54, QED 0.47