lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)C[C@H](C(=O)N1CC[C@@H](CCc2ccc3c(n2)NCCC3)C1)c1cccc(Cl)c1
InChIKey: ZMWIYVLLRRYJEL-IERDGZPVSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Inhibition of human alphavbeta5 integrin stably expressed in human K562 cells assessed as inhibition of cell adhesion to vitronectin incubated for 30 mins by BCECF-AM staining based fluorescence assay
Measurement: IC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 441.96, ALogP 4.13, HBA 4, HBD 2, PSA 82.53, QED 0.67
Compound (SMILES): Cc1ccc(C#Cc2cc(-c3nn(-c4nc(C(=O)O)cs4)c(CC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)ccc2F)o1
InChIKey: HFPSHJIHRRIMJL-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 634.69, ALogP 5.46, HBA 8, HBD 2, PSA 141.31, QED 0.22
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ncc(NC3CN(CCCF)C3)cc2F)N1CC(F)(F)CF
InChIKey: GGSBMAVBGZRJPI-MYYSRTQBSA-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 = 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 508.54, ALogP 4.49, HBA 5, HBD 2, PSA 60.08, QED 0.42
Compound (SMILES): COc1cc(/C=N/NC(N)=S)c(Br)c(Br)c1OC
InChIKey: AEEVFFOEEWVLGF-LNKIKWGQSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of GST-tagged human PARP2 incubated for 30 mins by chemiluminescence based UV/visible spectrophotometric analysis
Measurement: IC50 = 1560 nM (pChEMBL 5.809999942779541)
Descriptors: MW 397.09, ALogP 2.4, HBA 4, HBD 2, PSA 68.87, QED 0.46
Compound (SMILES): CC(C)(C)c1ccc(-c2cnc3c(c2)C=CS(=O)(=O)O3)cc1
InChIKey: CVZYJFKHKWRJCT-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 315.39, ALogP 3.74, HBA 4, HBD 0, PSA 56.26, QED 0.75
Compound (SMILES): CC(C)Nc1cncc(-c2cnc3[nH]nc(-c4cc5c(-c6ccccc6F)ccnc5[nH]4)c3c2)c1
InChIKey: RGQTUIWILOQDKF-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: 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 medium containing 1% fetal bovine serum and incubated overnight at 37° C. and 5% CO2. Following incubation, 20 μl of BrightGlo luminescence reagent (Promega) 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 > 10000 nM (pChEMBL 5)
Descriptors: MW 463.52, ALogP 6.19, HBA 5, HBD 3, PSA 95.17, QED 0.28
Compound (SMILES): COC(=O)[C@@H]1C=C(OC(=O)c2ccc(Cl)cc2)C(=O)[C@H]2[C@@]1(C)CC[C@H]1C(=O)O[C@H](c3ccoc3)C[C@]21C
InChIKey: BOCYEZMQXKXOGK-JXSGGZGWSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human mu opiod receptor expressed in CHO-K1 cells assessed as stimulation of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 526.97, ALogP 5.07, HBA 8, HBD 0, PSA 109.11, QED 0.4
Compound (SMILES): Cc1ccc2nc(NCCN)c3ncc(C)n3c2c1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: OWHLFAMVTWAXBL-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 11B (SINGLE PROTEIN), Homo sapiens
UniProt: P21127
Assay: Selectivity interaction (Kinase Panel (competition binding assay)) EUB0000589aTFA CDK11B
Measurement: Kd = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 255.32, ALogP 1.87, HBA 5, HBD 2, PSA 68.24, QED 0.75
Compound (SMILES): C=C(F)COc1ccc2occc2c1[C@@H]1C[C@H]1CN.Cl
InChIKey: TYHARJBXULAQSC-XOZOLZJESA-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 = 585 nM (pChEMBL 6.230000019073486)
Descriptors: MW 261.3, ALogP 3.36, HBA 3, HBD 1, PSA 48.39, QED 0.9
Compound (SMILES): CCN(C)C(=O)OCC1CCN(Cc2ccccc2)CC1
InChIKey: FASDVEQGWLQBRA-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 290.41, ALogP 2.99, HBA 3, HBD 0, PSA 32.78, QED 0.84
Compound (SMILES): CCCNc1cc(Nc2ccc(C#N)cc2)nc(-c2ccccc2)n1
InChIKey: XGKXFPDFYZPOER-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 (unknown origin) expressed in MDCK-II cells assessed as potentiation of SN-38-induced cytotoxicity measured after 72 hrs by MTT assay
Measurement: EC50 = 15.3 nM (pChEMBL 7.820000171661377)
Descriptors: MW 329.41, ALogP 4.58, HBA 5, HBD 2, PSA 73.63, QED 0.69
Compound (SMILES): CCC(=O)N[C@H]1COC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)c(=O)n(C)c2n1
InChIKey: SQNWZTSMOSQWFC-UONOGXRCSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) expressed in KATO -III cells assessed as autophosphorylation after 1 hr incubation measured by Mesoscale discovery (MSD) assay
Measurement: IC50 = 377 nM (pChEMBL 6.420000076293945)
Descriptors: MW 522.39, ALogP 3.03, HBA 9, HBD 2, PSA 116.6, QED 0.49
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3cccc(C#Cc4ccc(C5CC5)s4)c3)nn(-c3nc(C(=O)O)cs3)c2CCC2CC2)cc1F
InChIKey: WNXURRQSPOLYHS-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 672.83, ALogP 6.75, HBA 8, HBD 2, PSA 128.17, QED 0.16
Compound (SMILES): CN1C(=O)CC[C@H]1C(=O)N1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: SWQNFSBHLVEMAL-YZUZCNPQSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Mus musculus
UniProt: P51450
Assay: General RORgamma SPA binding assay : The binding of potential ligands to RORγ is measured by competition with [3H]25-hydroxycholesterol (Perkin Elmer NET674250UC) using a scintillation proximity assay (SPA). The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromatography. 15 μg/well RORγ (A262-S507) is incubated with test compound at varying concentrations in 3-fold serial dilution, with final concentrations ranging from 16.6 μM to 0.28 nM, for 10 min at rt in PBS buffer (Invitrogen #14190-144) containing 0.5% fatty acid free BSA (Gemini Bio-Products, Cat. #700-107P) and 0.1% glycerol (Sigma Cat#G5516). 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 10 min. 10 mg/mL of Copper-His Tag-PVT beads (Perkin Elmer cat # RPNQ0095) are added, and the mixture is incubated for 60 min. The reaction is read on a TopCount Microplate scintillation plate reader (Perkin Elmer). The competition data of the test compound over a range of concentrations was plotted as percentage inhibition of radioligand specifically bound in the absence of test compound (percent of total signal). After correcting for non-specific binding, IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce [3H] 25-hydroxycholesterol specific binding by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 624.55, ALogP 4.95, HBA 4, HBD 0, PSA 74.76, QED 0.36
Compound (SMILES): CCNc1ncc2c(n1)N(C)CCN(c1cccc(O[C@H](CCNC)c3cccs3)c1)C2=O
InChIKey: JRMKRCWDAUYJRA-HXUWFJFHSA-N
Target: Voltage-dependent calcium channel subunit alpha-2/delta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54289
Assay: Binding Assay: α2δ-1: Binding Assay to Human α2δ-1 Subunit of Cav2.2 Calcium Channel.Human α2δ-1 enriched membranes (2.5 μg) were incubated with 15 nM of radiolabeled [3H]-Gabapentin in assay buffer containing Hepes-KOH 10 mM, pH 7.4.NSB (non specific binding) was measured by adding 10 μM pregabalin. After 60 min incubation at 27° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.Readings were performed in a Trilux 1450 Microbeta radioactive counter (Perkin Elmer).
Measurement: Ki = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 466.61, ALogP 3.8, HBA 8, HBD 2, PSA 82.62, QED 0.5
Compound (SMILES): CN1CCC[C@H](Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: XMRPPWFWJKGYOU-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 3.78, HBA 4, HBD 2, PSA 56.84, QED 0.76
Compound (SMILES): O=C(NO)c1ccc(CN2C(=O)c3cccc(F)c3C2=O)cc1-c1ccccc1
InChIKey: YSAJLBSZOVKZCD-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant human HDAC5 using Ac-LGK(TFA)-AMC as substrate pre-incubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 390.37, ALogP 3.41, HBA 4, HBD 2, PSA 86.71, QED 0.41
Compound (SMILES): CC(C)(C)c1ccc(C(=O)NCc2ccc(C(=O)NO)cc2)cc1
InChIKey: UQORXLBOLWWYOS-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 326.4, ALogP 3.03, HBA 3, HBD 3, PSA 78.43, QED 0.6
Compound (SMILES): Cc1cc(=O)oc2cc(NC(=O)/C=C/c3cccc(F)c3)ccc12
InChIKey: ZMRVAQZEEHVLMS-VMPITWQZSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 538.7 nM (pChEMBL 6.269999980926514)
Descriptors: MW 323.32, ALogP 3.89, HBA 3, HBD 1, PSA 59.31, QED 0.59
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CC3)CC(=O)c3ccccc3O4)cc2)cc1
InChIKey: CEVBGMGJZAYACN-MHZLTWQESA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q76JU9
Assay: Agonist activity at Prolink-tagged mouse GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 523.63, ALogP 5.85, HBA 5, HBD 1, PSA 76.07, QED 0.37
Compound (SMILES): Cc1cc(NC(=N)N)nc2ccc(Cl)cc12
InChIKey: ZSNUZKGXUCSGJW-UHFFFAOYSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9EQD2
Assay: Binding affinity to rat NPFFR2 by radioligand binding assay
Measurement: Ki = 282 nM (pChEMBL 6.550000190734863)
Descriptors: MW 234.69, ALogP 2.5, HBA 2, HBD 3, PSA 74.79, QED 0.52
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: VMTBHEBGKDRQTD-LJQANCHMSA-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 = 65000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 403.49, ALogP 3.7, HBA 5, HBD 2, PSA 87.22, QED 0.68
Compound (SMILES): C#CCNc1cccc(C)c1Nc1ncc(OCc2c(Cl)c(OC)cc(OC)c2Cl)cn1
InChIKey: CBQPZQMSLKAGPC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human His-tagged FGFR3 (399 to 806 residues) cytoplasmic domain expressed in baculovirus expression system using Tyr 04 peptide as substrate after 1 hr in presence of ATP by Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 473.36, ALogP 5.48, HBA 7, HBD 2, PSA 77.53, QED 0.4
Compound (SMILES): FC(F)(F)c1cnc(N[C@@H]2CNC[C@H](c3nnc4ccccn34)C2)nc1-c1c[nH]c2ccccc12
InChIKey: IJQBKJGUIDXXLI-CABCVRRESA-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 478.48, ALogP 4.24, HBA 7, HBD 3, PSA 95.82, QED 0.36
Compound (SMILES): Brc1cnc(N[C@@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: XUBDCIJPSUUTBA-LLVKDONJSA-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 372.27, ALogP 3.55, HBA 4, HBD 3, PSA 65.63, QED 0.66
Compound (SMILES): COc1ncc(-c2nc(N3CCOCC3)c3ncn(CCCCCCC(=O)NO)c3n2)cn1
InChIKey: BFQLNFXKRXENAT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PI3Kalpha incubated for 1 hr by ADP-Glo kinase assay
Measurement: IC50 = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 456.51, ALogP 1.58, HBA 11, HBD 2, PSA 140.41, QED 0.26
Compound (SMILES): C#Cc1cnc(N[C@H]2CCCNC2)nc1-c1cn(C)c2ccccc12
InChIKey: NCOIDVUPFYMHRJ-HNNXBMFYSA-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 331.42, ALogP 2.78, HBA 5, HBD 2, PSA 54.77, QED 0.72
Compound (SMILES): CC1(C(=O)N2CCC[C@@H](c3nc(-c4ccc(C(=O)Nc5cc(C(F)(F)F)ccn5)cc4F)c4c(N)nccn34)C2)COC1
InChIKey: XYFZVVYVIFJBIS-QGZVFWFLSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Inhibition of human BLK
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 597.57, ALogP 4.53, HBA 8, HBD 2, PSA 127.74, QED 0.32
Compound (SMILES): N#Cc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2n1
InChIKey: LBVWNRFNOZHXGU-NSHDSACASA-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 387.37, ALogP 3.07, HBA 6, HBD 3, PSA 102.31, QED 0.64
Compound (SMILES): CC(C)Nc1cncc(-c2cc3c(-c4cc5c(-c6cccnc6)ccnc5[nH]4)n[nH]c3cn2)c1
InChIKey: DVQCABAXPPDZEI-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: 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 medium containing 1% fetal bovine serum and incubated overnight at 37° C. and 5% CO2. Following incubation, 20 μl of BrightGlo luminescence reagent (Promega) 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 > 10000 nM (pChEMBL 5)
Descriptors: MW 446.52, ALogP 5.45, HBA 6, HBD 3, PSA 108.06, QED 0.33
Compound (SMILES): O=C(Nc1ccccc1)OC1CCN(C2Cc3ccccc3C2)CC1
InChIKey: MEQMHNDIDFKKBK-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 336.44, ALogP 3.87, HBA 3, HBD 1, PSA 41.57, QED 0.93
Compound (SMILES): Cn1cc(-c2ccc3c(Nc4cccc(NC(=O)Nc5cccc(F)c5)c4)ncnc3c2)cn1
InChIKey: CGDYRZUPKPBLND-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 >= 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 453.48, ALogP 5.56, HBA 6, HBD 3, PSA 96.76, QED 0.32
Compound (SMILES): Cc1nnc(-c2ccc3cnc(NC(=O)c4ccnc(C5=CCN(C)CC5)c4)cc3c2)s1
InChIKey: FODAKPNZAKJZKF-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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 442.55, ALogP 4.43, HBA 7, HBD 1, PSA 83.9, QED 0.5
Compound (SMILES): Clc1ccc2c(c1)CCCc1nnc([C@H]3CC[C@H](Oc4ccccn4)CC3)n1-2
InChIKey: XPJLLCAORNNZCL-RZDIXWSQSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: Displacement of [3H]AVP from human V2a receptor expressed in 1132N1 cells assessed as dissociation constant by radioligand binding assay
Measurement: Ki = 560 nM (pChEMBL 6.25)
Descriptors: MW 394.91, ALogP 4.91, HBA 5, HBD 0, PSA 52.83, QED 0.63
Compound (SMILES): Cc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c12
InChIKey: QPXJKYBERAQULM-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 375.4, ALogP 4.12, HBA 4, HBD 3, PSA 65.63, QED 0.64
Compound (SMILES): O=S(=O)(c1cccc(Cl)c1)n1c(-c2ccccc2)nc2c(N3CCNCC3)nccc21
InChIKey: JHVGQSBTPJECOW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT2A expressed in HEK293 cell membranes incubated for 1 hr by micro-beta plate reader based analysis
Measurement: Ki = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 453.95, ALogP 3.4, HBA 7, HBD 1, PSA 80.12, QED 0.51
Compound (SMILES): CC(C)(C)n1cc2c(n1)C(=O)CC1(CCN(C(=O)c3ccnc(-c4ccc(C(=O)O)cc4)c3)CC1)O2
InChIKey: FIAQCQHMUMHZHV-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition of recombinant human ACC1 using acetyl coA as substrate incubated for 1 hr by transcreener fluorescence polarization assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 488.54, ALogP 4.04, HBA 7, HBD 1, PSA 114.62, QED 0.59
Compound (SMILES): C[C@H]1CN(CC[C@H]2CC[C@H](NC(=O)N(C)C)CC2)CCc2ccc(Cl)cc21
InChIKey: IDTLNOOYTVGUDL-ZWOKBUDYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]methyl-spiperone from recombinant human D3 receptor expressed in CHO cells
Measurement: Ki = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 391.99, ALogP 4.52, HBA 2, HBD 1, PSA 35.58, QED 0.82
Compound (SMILES): O=C(NO)c1ccc(Nc2c3c(nc4ccccc24)CCCC3)cc1
InChIKey: CZOYPJGGAMPDBF-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC9 (604 to 1066 residues) expressed in baculovirus infected Sf9 cells using fluorogenic HDAC 2A substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 333.39, ALogP 3.98, HBA 4, HBD 3, PSA 74.25, QED 0.5
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: VJUGSZWVYVMRBR-WSUOKSENSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Antagonist activity at human MC4R expressed in HEK293 cells expressing the GScAMP22F cAMP reporter assessed as reduction in alpha-MSH-induced cAMP accumulation by cAMP split-luciferase reporter gene assay
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 1088.29
Compound (SMILES): O=C(Nc1cncc(-c2cnc3[nH]nc(-c4cc5cccnc5[nH]4)c3c2)c1)C1CCCCC1
InChIKey: BOURDPARWUPIHI-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: 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 medium containing 1% fetal bovine serum and incubated overnight at 37° C. and 5% CO2. Following incubation, 20 μl of BrightGlo luminescence reagent (Promega) 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 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 437.51, ALogP 5.08, HBA 5, HBD 3, PSA 112.24, QED 0.36
Compound (SMILES): Cc1c(C(=O)/C=C/NNC(=O)c2ccc(S(N)(=O)=O)cc2)sc2nc3ccccc3n12
InChIKey: HONZNOSFAUYNLA-ZHACJKMWSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 54.8 nM (pChEMBL 7.260000228881836)
Descriptors: MW 455.52, ALogP 2.14, HBA 8, HBD 3, PSA 135.66, QED 0.23
Compound (SMILES): Cc1cc2cc(NC(=O)c3cccnc3N)ccc2[nH]1
InChIKey: GWHPATATCVJNBI-UHFFFAOYSA-N
Target: Transitional endoplasmic reticulum ATPase (SINGLE PROTEIN), Homo sapiens
UniProt: P55072
Assay: Competitive inhibition of recombinant human full length Avi-tagged p97 (1 to 806 residues) expressed in Escherichia coli Rosetta 2(DE3) using 20 uM ATP as substrate incubated for 90 mins by ADP-glo assay based Michaelis-Menten plot analysis
Measurement: Ki = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 266.3, ALogP 2.71, HBA 3, HBD 3, PSA 83.8, QED 0.67
Compound (SMILES): NS(=O)(=O)c1ccc(-n2c(SCC(=O)Nc3ccc([N+](=O)[O-])cc3[N+](=O)[O-])nc3ccc(I)cc3c2=O)cc1
InChIKey: OHNDOHSJEPNGKJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 682.43, ALogP 3.18, HBA 11, HBD 2, PSA 210.43, QED 0.09
Compound (SMILES): CN(Cc1ccc2nccn2c1)c1nnc(-c2ccc(OC3CCCC3)cc2)o1
InChIKey: JQZDMXCJPPAMOF-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of His6/TEV fused-GST-tagged Flt3 (unknown origin) (H564 to S993 residues) using Axltide (CKKSRGDYMTMQJ-acid) peptide as substrate preincubated for 30 mins followed by substrate and ATP addition at Km concentration measured after 75 mins by RapidFire LC-MS analysis
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 389.46, ALogP 4.34, HBA 7, HBD 0, PSA 68.69, QED 0.49
Compound (SMILES): Cn1nc(CN2CCCC2)nc1-c1ccc(C(C)(C)C)cc1
InChIKey: VDGWYCOTDATRIF-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma-1 receptor in guinea pig brain membranes incubated for 1 hr in presence of 250 uM phenytoin liquid scintillation counting method
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 298.43, ALogP 3.38, HBA 4, HBD 0, PSA 33.95, QED 0.87
Compound (SMILES): COc1ccccc1C1c2c(C(C)(C)C)n[nH]c2C(=O)N1c1ccc(-c2nccs2)cc1
InChIKey: XDHCNCFXESDQGE-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 444.56, ALogP 5.59, HBA 5, HBD 1, PSA 71.11, QED 0.45
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCN(c3ccc(F)cc3F)C2=O)cc1
InChIKey: SGCKOJXZNTVQLM-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human CAH4 expressed in Escherichia coli BL21 (DE3) by stopped flow CO2 hydration assay
Measurement: Ki = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 353.35, ALogP 2.06, HBA 3, HBD 1, PSA 83.71, QED 0.92
Compound (SMILES): Cn1cc(-c2ccccc2Oc2ccccc2)c2cc(C(=O)NCCCCC(=O)NO)[nH]c2c1=O
InChIKey: IEVUMROHFZOVMK-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 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 474.52, ALogP 3.73, HBA 6, HBD 4, PSA 125.45, QED 0.17
Compound (SMILES): COc1ccc2cc(C(=O)NCCN(C)C)oc2c1.CS(=O)(=O)O
InChIKey: QYDNZUNQDSSNPX-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using omeprazole as substrate incubated for 5 mins followed by NADPH addition and measured after 20 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 262.31, ALogP 1.73, HBA 4, HBD 1, PSA 54.71, QED 0.89
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)c(F)c2)cc1
InChIKey: ODKHJVBQRWOSHU-MHZLTWQESA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Agonist activity at Prolink-tagged rat GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 509.62, ALogP 6.55, HBA 3, HBD 1, PSA 49.77, QED 0.35
Compound (SMILES): CCn1nc2c(c1Nc1nc(-c3ccc(-n4cnc(C)c4)c(OC)n3)cs1)C(C)CC2(C)C
InChIKey: NONHWESJQFIAJQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin) by fluorescence-based assay
Measurement: IC50 = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 463.61, ALogP 5.45, HBA 9, HBD 1, PSA 82.68, QED 0.41
Compound (SMILES): C[C@H](CN1CCC[C@@H]1C)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: DBWSFWPXCPNWRZ-NEPJUHHUSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using Ac-Arg-Gly-Lys(Ac) as substrate by fluorogenic assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 382.39, ALogP 3.36, HBA 5, HBD 1, PSA 71.26, QED 0.86
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccccc4)CC3)cc2C1=O
InChIKey: SJQGLRPDBHCHCW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Receptor Binding Assay: 5-HT1A: (1) The prepared membrane was applied with appropriate amount of buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of 5-HT (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-8-OH-DPAT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each reaction tube was incubated at 37° C. for 10 min; after the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki = 569 nM (pChEMBL 6.25)
Descriptors: MW 379.5, ALogP 2.91, HBA 4, HBD 0, PSA 36.02, QED 0.72
Compound (SMILES): CC(=O)N[C@H]1CCC[C@@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(Cl)cn2)C1
InChIKey: AVIWDYSJSPOOAR-CABCVRRESA-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 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 429.95, ALogP 3.81, HBA 5, HBD 2, PSA 88.91, QED 0.77
Compound (SMILES): CN1CCN(CCCOc2ccc(N3C(=O)S/C(=C\c4ccc(Oc5ccc(C#N)cc5)cc4)C3=O)cc2)CC1
InChIKey: HACZQYUWEAIJNO-ANYBSYGZSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Allosteric inhibition of IKKbeta (unknown origin) using 5FAM-GRHDSGLDSMK-NH2 as substrate incubated for 10 mins followed by substrate addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 204.17 nM (pChEMBL 6.690000057220459)
Descriptors: MW 554.67, ALogP 5.61, HBA 8, HBD 0, PSA 86.11, QED 0.25
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(C#CC#Cc3cnc([C@@H]4CCCN4C(=O)[C@H](NC(=O)OC)c4ccccc4)[nH]3)c(-c3ccc(N(C)C)cc3)c2)[nH]1)C(C)C.Cl.Cl
InChIKey: VUZGGQLEFRAGSK-RVKOZSAISA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 2a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.0128 nM (pChEMBL 10.890000343322754)
Descriptors: MW 864.02, ALogP 6.74, HBA 9, HBD 4, PSA 177.88, QED 0.1
Compound (SMILES): CN(C)S(=O)(=O)c1ccc2c(c1)/C(=C/c1cn(C)c3ccc(O)cc13)C(=O)N2
InChIKey: JNYJJXLTWZLGQH-IUXPMGMMSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TrkC (unknown origin)
Measurement: IC50 = 9.72 nM (pChEMBL 8.010000228881836)
Descriptors: MW 397.46, ALogP 2.63, HBA 5, HBD 2, PSA 91.64, QED 0.66
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(CC#N)C3)nc1-c1cnn(C(C)C)c1
InChIKey: YBNNEVCRUSEFPL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (808 to end residues) KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate measured after 40 mins in presence of [gamm33P]ATP by scintillation counting method
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 387.49, ALogP 3.85, HBA 7, HBD 1, PSA 82.66, QED 0.67
Compound (SMILES): CC(C)CCOc1nc(N2C[C@@H]3[C@H](C2)[C@H]3C(=O)O)ccc1C(=O)NC1C2CC3CC1CC(O)(C3)C2
InChIKey: IXFGEDLOELTAGL-JPCUSUTFSA-N
Target: Glucose-6-phosphate 1-dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: P11413
Assay: Inhibition of wild type G6PD (unknown origin) using alpha-ketoglutarate and NADPH incubated for 30 mins by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 483.61, ALogP 2.94, HBA 6, HBD 3, PSA 111.99, QED 0.52
Compound (SMILES): CCN(CC)Cc1ccc(OC)c(-c2cc3c(-c4ccc(C(=O)O)c(C(C)C)c4)ccnc3[nH]2)c1
InChIKey: XKLPRHHLSQBUIC-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 2415 nM (pChEMBL 5.619999885559082)
Descriptors: MW 471.6, ALogP 6.57, HBA 4, HBD 2, PSA 78.45, QED 0.29
Compound (SMILES): N=C(N)Nc1cccc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: BMHOPYDAWFKHEW-OALUTQOASA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Cell adhesion assay to Hamster Ovary: The blockade of integrin alpha 5 beta 1 provides a novel target for the treatment of asthma. As shown in FIGS. 1A and 1B, delivery of ATN-161, a low affinity yet specific inhibitor of alpha5beta1, reduces the magnitude of airway narrowing in vivo in mice sensitized and challenged with ovalbumin, a widely used model of allergic asthma. In the same model, it was found that mice with a specific deletion of this integrin in smooth muscle also have reduced airway narrowing. The intracellular actin-myosin cross-bridging pathway serves as a useful target. Modulating the interactions of the cell and the extracellular matrix impairs the ability of the smooth muscle to transmit tension effectively. The blockade of integrin alpha 5 beta 1 was tested in vitro with human cell lines as well as in vivo with a mouse model of airway hyperresponsiveness. Novel compounds as described herein, and identified in Table 1, have been synthesized and tested in vitro for their ability to inhibit cell adhesion mediated by alphavbeta1 (adhesion of Chinese Hamster Ovary cells transfected with human alphav to the latency associated peptide of transforming growth factor beta, a response that is entirely dependent on binding of alphavbeta1 to LAP).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 559.61, ALogP -0.74, HBA 7, HBD 7, PSA 223.88, QED 0.14
Compound (SMILES): Nc1nn2c(-c3ccc(Cl)cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: ANPPRZRKIIVFGL-WCWDXBQESA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E (unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate in presence of [gamma33P]ATP
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 427.88, ALogP 3.69, HBA 8, HBD 2, PSA 141.09, QED 0.48
Compound (SMILES): O=C(c1ccc(Cc2ccccc2)cc1)C1CCN(C(=O)c2cc(O)ccc2F)CC1
InChIKey: WXGIEJRIHVXHRR-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of FAAH in human U937 cells assessed as reduction in [3H]ethanolamine formation using [ethanolamine-1-3H]AEA as substrate incubated for 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.48, ALogP 4.86, HBA 3, HBD 1, PSA 57.61, QED 0.6
Compound (SMILES): Cc1c(-c2nn(-c3ccccc3)cc2/C=N/O)nnn1-c1ccc(F)cc1
InChIKey: ZGPJDLWDSKSSOK-SRZZPIQSSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow carbon dioxide hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 362.37, ALogP 3.38, HBA 7, HBD 1, PSA 81.12, QED 0.34
Compound (SMILES): Cc1ccc(NC(=O)c2ccc(C)c(C(F)(F)F)c2)cc1C#Cc1nn([C@H]2CC[C@H](O)CC2)c2ncnc(N)c12
InChIKey: YHVHYWYQEFELOW-HZCBDIJESA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Inhibition of human full length recombinant LYN using poly(Glu,Tyr)4:1 as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 548.57, ALogP 5.17, HBA 7, HBD 3, PSA 118.95, QED 0.3
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1Cl
InChIKey: ONRGJWZQIHEWQH-MRXNPFEDSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 421.89, ALogP 3.73, HBA 5, HBD 2, PSA 87.22, QED 0.61
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccc(NC(=O)CCCCCC(=O)NO)cc3C2)c(O)cc1O
InChIKey: AMNFQPNPGQJGOD-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using RHK-K(Ac)-AMC as substrate by fluorescence based assay
Measurement: IC50 = 2011 nM (pChEMBL 5.699999809265137)
Descriptors: MW 469.54, ALogP 3.77, HBA 6, HBD 5, PSA 139.2, QED 0.22
Compound (SMILES): CN(C)CCOc1ccc(-c2cc(=O)c3c(O)cc(OCCCCCC(=O)NO)cc3o2)cc1.Cl
InChIKey: HDHBTUFDSFLMOP-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant human N-terminal GST-tagged HDAC-5 (617 to end residues) expressed in baculovirus infected in Sf9 cells using Boc-Lys (q-Ac)-AMC as substrate incubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 470.52, ALogP 3.55, HBA 8, HBD 3, PSA 121.47, QED 0.21
Compound (SMILES): Nc1nccc(COc2ccc3nc(N[C@@H]4CCCC[C@H]4O)sc3c2Cl)c1Cl
InChIKey: QYCFHBDOJSLVRL-DGCLKSJQSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human PDGFRbeta phosphorylation in PDGF-DD induced human HEK293-TetR cells incubated for 1 hr followed by PDGF-DD stimulation and measured after 5 mins by HTRF assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 439.37, ALogP 4.87, HBA 7, HBD 3, PSA 93.29, QED 0.53
Compound (SMILES): OC(CNC1CCN(CCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1)Cc1ccccc1
InChIKey: GHMRSCYBFHYOPJ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human D3 receptor expressed in HEK293 cell membranes measured after 60 mins by microbeta scintillation counting method
Measurement: Ki = 701 nM (pChEMBL 6.150000095367432)
Descriptors: MW 496.67, ALogP 5.45, HBA 4, HBD 2, PSA 35.5, QED 0.37
Compound (SMILES): Cc1ccc(S(=O)(=O)n2ccc3ccc(CO[C@H](C(=O)O)[C@H](N)C(=O)O)cc32)cc1.Cl
InChIKey: FZPVYWKWFZZYRV-APTPAJQOSA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43004
Assay: Inhibition of human EAAT2 transfected in HEK293 cells assessed as inhibition of [3H]-D-aspartate uptake incubated for 4 mins by TopCount scintillation counting analysis
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 432.45, ALogP 1.57, HBA 7, HBD 3, PSA 148.92, QED 0.49
Compound (SMILES): O=C1c2c(Br)c(Br)c(Br)c(Br)c2C(=O)C1(O)O
InChIKey: ZTTWUCSGHUBHMY-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 46700 nM (pChEMBL 4.329999923706055)
Descriptors: MW 493.73, ALogP 2.8, HBA 4, HBD 2, PSA 74.6, QED 0.25
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)N/N=C/c2ccccn2)cc1
InChIKey: HTRWIOXPFBBBCH-CCVNUDIWSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged human recombinant full length PI3Kdelta co-expressed with human recombinant full length P85alpha in baculovirus infected Sf21 cells using PIP2 peptide as substrate incubated for 2 hrs in presence ATP by ADP-Glo Kinase Assay
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 499.56, ALogP 3.46, HBA 9, HBD 3, PSA 144.21, QED 0.27
Compound (SMILES): CCCCCCCCCCCCCC(=S)NCCCC[C@H](NC(=O)CCOCCOCCNc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O)C(=O)Nc1ccccc1
InChIKey: GIYJZXALTTVTFT-AIQPRDSRSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of human SIRT2 defatty-acylation activity using peptide substrate in presence of NAD+ by HPLC analysis
Measurement: IC50 > 83000 nM (pChEMBL 4.080999851226807)
Descriptors: MW 863.13, ALogP 6.83, HBA 10, HBD 5, PSA 184.27, QED 0.03