lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): c1ccc2c(NCCCCCSSCCCCCNc3c4c(nc5ccccc35)CCCC4)c3c(nc2c1)CCCC3
InChIKey: CSHQXRFENGZQAM-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Mixed-type inhibition of electric eel AChE assessed as enzyme-substrate-inhibitor complex using p-nitrophenyl acetate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 598.93, ALogP 9.79, HBA 6, HBD 2, PSA 49.84, QED 0.1
Compound (SMILES): CC(C)[C@H](NC(=O)C(F)(F)F)[C@H](Oc1ccc2c(cnn2-c2ccc(=O)n(C)c2)c1)c1cccc(Cl)c1
InChIKey: DPAAYBADQOGZSY-BJKOFHAPSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Displacement of fluormone RED from human full length glucocorticoid receptor after 4 hrs by fluorescence polarization assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 532.95, ALogP 5.2, HBA 6, HBD 1, PSA 78.15, QED 0.35
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)Cc2ccccc2Nc2c(Cl)cccc2Cl)cc1
InChIKey: TZWKNAVYTUOLLG-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 catalytic domain incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 450.35, ALogP 4.57, HBA 4, HBD 3, PSA 101.29, QED 0.51
Compound (SMILES): NS(=O)(=O)c1ccc(OCCCNC(=O)Cc2ccccc2Nc2c(Cl)cccc2Cl)cc1
InChIKey: VRBIGEFOPTXOQN-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 catalytic domain incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 137.1 nM (pChEMBL 6.860000133514404)
Descriptors: MW 508.43, ALogP 4.51, HBA 5, HBD 3, PSA 110.52, QED 0.35
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccccc2NC(=O)CCO)n1
InChIKey: KIWWMQZDDHWGPB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 2120 nM (pChEMBL 5.670000076293945)
Descriptors: MW 513, ALogP 3.75, HBA 9, HBD 3, PSA 112.08, QED 0.39
Compound (SMILES): NC(=O)c1ccc(OCc2ccccc2F)cc1
InChIKey: ARHAVVDXPGTLBI-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of N-terminal His-tagged human ARTD1 (1 to 1014 residues) expressed in Escherichia coli Rosetta2 (DE3) using activated DNA as substrate after 1.5 hrs in presence of NAD+
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 245.25, ALogP 2.5, HBA 2, HBD 1, PSA 52.32, QED 0.9
Compound (SMILES): O=C(NCCN1CCN(c2ccc(Cl)c(Cl)c2)CC1)c1ccccn1
InChIKey: WJTVOECAMUQNOG-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]SCH-23390 from human recombinant dopamine D1 receptor expressed in CHO cells
Measurement: Ki = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 379.29, ALogP 2.94, HBA 4, HBD 1, PSA 48.47, QED 0.87
Compound (SMILES): O=C(N/N=C/c1ccc2ccccc2c1)c1ccc(O)cc1
InChIKey: RNZIMBFHRXYRLL-XDHOZWIPSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Agonist activity at ERR-alpha (unknown origin) expressed in HEK293 cells co-transfected with luciferase reporter plasmid incubated for 24 hrs by one-glo luciferase reporter assay
Measurement: EC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 290.32, ALogP 3.31, HBA 3, HBD 2, PSA 61.69, QED 0.57
Compound (SMILES): Cl.FCCOc1ccccc1CCC1CCN(CCc2ccccc2)CC1
InChIKey: LNYIZUKIJVITIU-UHFFFAOYSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q01827
Assay: Inhibition of [3H]dopamine uptake at VMAT2 in rat striatal synaptic vesicles by scintillation spectrometry
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 355.5, ALogP 4.92, HBA 2, HBD 0, PSA 12.47, QED 0.63
Compound (SMILES): N#Cc1ccc(-c2cnc3ccc(-c4ccc(C(=O)N5CCNCC5)cc4)nn23)cc1
InChIKey: TVBANCDFRJJEKJ-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Inhibition of GST-tagged MNK2 (72 to 385 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) using JH3 peptide as substrate preincubated for 10 mins followed by substrate and ATP addition measured after 60 mins
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 408.47, ALogP 2.98, HBA 6, HBD 1, PSA 86.32, QED 0.56
Compound (SMILES): CCOC(=O)[C@@H]1CN(CCn2c(=O)[nH]c3ccccc3c2=O)CC[C@@H]1c1cccc(C(F)(F)F)c1
InChIKey: SMJPJSDEOFDSNC-UYAOXDASSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q05940
Assay: Inhibition of human VMAT2 expressed in HEK293 cell membranes assessed as reduction in [3H[-5HT uptake pre-incubated for 10 mins before [3H[-5HT addition and measured after 6 mins
Measurement: IC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 489.49, ALogP 3.38, HBA 6, HBD 1, PSA 84.4, QED 0.54
Compound (SMILES): O=C(CCN1CCc2ccccc2C1c1ccc(-c2ccccc2)cc1)NO
InChIKey: OXWJYPZJWHSXBJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant HDAC8 (unknown origin) expressed in Escherichia coli using fluor de Lys(R) as substrate pretreated for 5 mins followed by substrate addition measured after 35 mins by fluorescence assay
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 372.47, ALogP 4.2, HBA 3, HBD 2, PSA 52.57, QED 0.52
Compound (SMILES): COc1ccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@@H](NC(=O)C(C)(F)F)C(C)C)cn1
InChIKey: GDLMXSZEDBKHNY-LOSJGSFVSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Transrepression activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells assessed as inhibition of PMA-stimulated gene expression incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: IC50 = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 512.53, ALogP 5.48, HBA 6, HBD 1, PSA 78.27, QED 0.32
Compound (SMILES): CC(C)=CCC/C(C)=C/CCn1cc(CC(C)(P(=O)([O-])[O-])P(=O)([O-])[O-])nn1.[Na+].[Na+].[Na+].[Na+]
InChIKey: YBGYJINSIKVFSV-GPZOHOMCSA-J
Target: Farnesyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: P14324
Assay: Inhibition of recombinant FDPS (unknown origin) using GPP as substrate pretreated for 10 mins followed by substrate addition measured after 30 mins in presence of [14C]-IPP by liquid scintillation counting method
Measurement: IC50 = 43100 nM (pChEMBL 4.369999885559082)
Descriptors: MW 421.37, ALogP 2.98, HBA 5, HBD 4, PSA 145.77, QED 0.33
Compound (SMILES): COc1cc2c(NC3CCC34CCN(C)CC4)cc(-c3ccc(C)o3)nc2cc1OCCCN1CCCC1
InChIKey: FWEMDGGXZBEQDX-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Inhibition of human DNMT1 using polydeoxyinosine polydeoxycytosine DNA as substrate after 15 mins in presence of SAM by TR-FRET assay
Measurement: IC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 518.7, ALogP 5.96, HBA 7, HBD 1, PSA 63, QED 0.35
Compound (SMILES): CNC(=O)c1ccc(-c2cc3cccc(-c4nn(C5CCOCC5)c5c4CN(C(C)=O)CC5)c3cn2)cn1
InChIKey: MUJXZEDIWKGKQD-UHFFFAOYSA-N
Target: ATPase family AAA domain-containing protein 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULI0
Assay: Binding affinity to human partial length ATAD2B (Q955 to R1082 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 510.6, ALogP 3.78, HBA 7, HBD 1, PSA 102.24, QED 0.45
Compound (SMILES): CNc1ncc2c(-c3ccc(N4CCN(C)CC4)nc3)nn(CC3CCCC3)c2n1
InChIKey: UGPDJIJFANODJH-UHFFFAOYSA-N
Target: Epithelial discoidin domain-containing receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q08345
Assay: Inhibition of wild-type human partial length DDR1 (R565 to V876 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 406.54, ALogP 2.87, HBA 8, HBD 1, PSA 75, QED 0.7
Compound (SMILES): NS(=O)(=O)c1ccc(/N=C2\NC(=O)/C(=C3/C(=O)Nc4ccc(Cl)cc43)S2)cc1
InChIKey: LMASTTSQUHZWAS-YPKPFQOOSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human transmembrane carbonic anhydrase 9 by stopped-flow CO2 hydrase assay
Measurement: Ki = 62.4 nM (pChEMBL 7.210000038146973)
Descriptors: MW 434.89, ALogP 2.2, HBA 6, HBD 3, PSA 130.72, QED 0.62
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCCCC2)NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: ONUUGLJKQIIBGJ-ILOBPARPSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 916.06, ALogP 0.47, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): O=C(CCCCCCNCc1ccccc1)NO
InChIKey: SNLPPFAZSJSJSF-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant HDAC8 (unknown origin) expressed in Escherichia coli using fluor de Lys(R) as substrate pretreated for 5 mins followed by substrate addition measured after 35 mins by fluorescence assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 250.34, ALogP 2.23, HBA 3, HBD 3, PSA 61.36, QED 0.36
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc3c(cc12)C(C)OC(CO)CN3S(C)(=O)=O
InChIKey: LEGFVEQZPWXYTI-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 1b NS5B polymerase infected in human HuH7 replicon cells by luciferase reporter gene assay
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 462.5, ALogP 2.82, HBA 6, HBD 2, PSA 109.08, QED 0.62
Compound (SMILES): Cc1cc(CC(=O)Nc2ccn(Cc3ccc(C#N)cn3)n2)ccc1OCC(F)(F)F
InChIKey: ATAZIWXKOZRZRN-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of recombinant Cav1.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by KCl addition by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 3310 nM (pChEMBL 5.480000019073486)
Descriptors: MW 429.4, ALogP 3.63, HBA 6, HBD 1, PSA 92.83, QED 0.62
Compound (SMILES): CCc1cc(-c2ccoc2)nc(N2CCN(C)CC2)n1
InChIKey: GOZPYYFAYISDDO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in HEK293 cells incubated for 1 hr
Measurement: Ki = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 272.35, ALogP 2.05, HBA 5, HBD 0, PSA 45.4, QED 0.86
Compound (SMILES): Cc1cc(=O)oc2cc(OCc3cc[n+](Cc4ccccc4Br)cc3)ccc12.[Br-]
InChIKey: HGSMDYBCEIXINY-UHFFFAOYSA-M
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated for 6 mins followed by substrate addition measured up to 180 secs by Ellman's method
Measurement: IC50 = 78.1 nM (pChEMBL 7.110000133514404)
Descriptors: MW 437.31, ALogP 4.78, HBA 3, HBD 0, PSA 43.32, QED 0.33
Compound (SMILES): CCCCOc1ccc(C(=O)Nc2c(-c3cccs3)nc3ccc(Br)cn23)cc1
InChIKey: PUSUWSQYMQZASP-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6/beta-3/gamma-2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P18508
Assay: Displacement of [3H]EBOB from rat GABA-A receptor alpha6beta3gamma2 expressed in HEK293 cell membranes after 90 mins in presence of GABA by liquid scintillation counting analysis
Measurement: IC50 = 4340 nM (pChEMBL 5.360000133514404)
Descriptors: MW 470.39, ALogP 6.26, HBA 5, HBD 1, PSA 55.63, QED 0.32
Compound (SMILES): CCNCCc1c(C(=O)NCc2ccccc2OCC(F)(F)F)nn(-c2ccccc2)c1-c1ccccc1
InChIKey: PYXDWIWBQXUGPX-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 (unknown origin)
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 522.57, ALogP 5.56, HBA 5, HBD 2, PSA 68.18, QED 0.25
Compound (SMILES): COc1ccccc1/C=C/C(=O)c1ccncc1
InChIKey: PVHPZPKHRNPXOT-VOTSOKGWSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in yeast microsomal membranes using 3-cyano-7-ethoxycoumarin as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 239.27, ALogP 2.99, HBA 3, HBD 0, PSA 39.19, QED 0.61
Compound (SMILES): CN(C)C1CCN(c2ccc(Nc3cc4c(N5CCC(CO)CC5)nc(Nc5ccc(F)cc5)nc4cn3)nc2)CC1
InChIKey: DXOUQSZKEPSXBC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR L858R/T790M/C797S mutant (unknown origin) using Poly (Glu, Tyr) as substrate after 40 mins by kinase-Glo luminescence assay
Measurement: IC50 = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 571.71, ALogP 4.79, HBA 10, HBD 3, PSA 105.57, QED 0.27
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Cc4ccc(C(=O)NO)c(F)c4)ccc3OCC)nc12
InChIKey: AFSIULIFJJDVHG-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of full length human recombinant N-terminal GST-tagged PDE5A1 expressed in baculovirus infected sf9 cells using cGMP as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 479.51, ALogP 3.52, HBA 7, HBD 3, PSA 122.13, QED 0.26
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)CC)N(C)C(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: UVEWXKOJMYQFGE-MLBLPCAVSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method
Measurement: Kd = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 1662.01
Compound (SMILES): c1cc(CC2CCC2)c2c(n1)N1CCNCC1CC2
InChIKey: WDUJNEUBVHIQQH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at recombinant 5-HT2A receptor (unknown origin) expressed in HEK293 cells assessed as increase in [3H]-inositol phosphate accumulation by scintillation counting method
Measurement: EC50 = 2510 nM (pChEMBL 5.599999904632568)
Descriptors: MW 257.38, ALogP 2.15, HBA 3, HBD 1, PSA 28.16, QED 0.88
Compound (SMILES): Cl.FCCOc1ccc(CCN2CCC(CCc3ccccc3)CC2)cc1
InChIKey: BDYZMACPOPKJEW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]Dofetilide from human ERG expressed in HEK293 cells after 60 mins by scintillation spectrometry
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 355.5, ALogP 4.92, HBA 2, HBD 0, PSA 12.47, QED 0.63
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(=O)N[C@@H](CN)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C)[C@@H](C)CC
InChIKey: RPBPANCRQFSQRK-RYWOMTJGSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Displacement of N-Flu-DOT1L from MBP-tagged ENL (unknown origin) (489 to 559 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 1240 nM (pChEMBL 5.909999847412109)
Descriptors: MW 820.09, ALogP 0.64, HBA 9, HBD 6, PSA 232.45, QED 0.1
Compound (SMILES): O=C(CC1CN(S(=O)(=O)c2ccc(F)cc2)c2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2S1)Nc1nncs1
InChIKey: VZANPRWREWRZMY-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at GAL4-tagged human LXRbeta assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 616.56, ALogP 4.69, HBA 8, HBD 2, PSA 112.49, QED 0.39
Compound (SMILES): CN1CC[C@@](O)(C#Cc2cccc(-n3nc(C(N)=O)c4cccnc43)c2)C1=O
InChIKey: QRHDTFFVGFIUKH-FQEVSTJZSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK in HEK-293 cells assessed as inhibition of NIK-dependent NF-kappaB response element expression by firefly luciferase reporter gene based analysis
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 375.39, ALogP 0.46, HBA 6, HBD 2, PSA 114.34, QED 0.63
Compound (SMILES): CC(=O)N1c2ccc(-c3ccco3)cc2[C@H](NC(=O)OC(C)C)C[C@@H]1C
InChIKey: OZBRAEGGHPSXJE-SUMWQHHRSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to His-tagged BRD2 bromodomain 2 (unknown origin) by SPR assay
Measurement: Kd = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 356.42, ALogP 4.27, HBA 4, HBD 1, PSA 71.78, QED 0.89
Compound (SMILES): NC(=O)Cc1ccc(Nc2cc(C(F)(F)F)nc(-c3cccc(Cl)c3)n2)cc1
InChIKey: KRRGWHSEDYQKDQ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Allosteric modulation of human PDE4D
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 406.8, ALogP 4.59, HBA 4, HBD 2, PSA 80.9, QED 0.65
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-c3c[nH]c4ccccc34)c12
InChIKey: YBBHADVVTLEPSZ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 409.45, ALogP 5.54, HBA 5, HBD 2, PSA 92.62, QED 0.4
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccc(NC(=O)CCOCc3ccccc3)cc2)n1
InChIKey: GCWJFCPMHSRKSB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 1430 nM (pChEMBL 5.840000152587891)
Descriptors: MW 603.12, ALogP 5.97, HBA 9, HBD 2, PSA 101.08, QED 0.19
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)O)c(OCC)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: HHBDPCCWQBHZLA-UYAOXDASSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 517.58, ALogP 3.67, HBA 7, HBD 4, PSA 158.41, QED 0.09
Compound (SMILES): Cl.N[C@@H]1CCC=C(c2ccc(F)cc2)[C@H]1CNc1cc(F)c(S(=O)(=O)Nc2nccs2)cc1Cl
InChIKey: LGCIKUFVGKSBFD-LJLRIERRSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 511.02, ALogP 5.11, HBA 6, HBD 3, PSA 97.11, QED 0.41
Compound (SMILES): O=C(NCCN1CCN(c2cccc(C(F)(F)F)c2)CC1)c1ccccn1
InChIKey: HBJPOHDQQVIBLT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Antagonist activity at 5-HT2A receptor in Sprague-Dawley rat ielum assessed as reduction in 5-HT-evoked contraction
Measurement: EC50 = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 378.4, ALogP 2.65, HBA 4, HBD 1, PSA 48.47, QED 0.87
Compound (SMILES): Cl.FCCOc1cccc(CCC2CCN(CCc3ccccc3)CC2)c1
InChIKey: PZDFSTACALGBGX-UHFFFAOYSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q01827
Assay: Inhibition of [3H]dopamine uptake at VMAT2 in rat striatal synaptic vesicles by scintillation spectrometry
Measurement: Ki = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 355.5, ALogP 4.92, HBA 2, HBD 0, PSA 12.47, QED 0.63
Compound (SMILES): CNC(=O)c1cc(OCCCCN2CCN(c3cccc4sccc34)CC2)ccn1
InChIKey: AOSUTZCGNCJEJR-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Antagonistic activity at alpha-1A adrenergic receptor (unknown origin) after 10 mins by FLIPR assay
Measurement: IC50 = 164 nM (pChEMBL 6.789999961853027)
Descriptors: MW 424.57, ALogP 3.64, HBA 6, HBD 1, PSA 57.7, QED 0.56
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)C2CCn3c(C(=O)c4ccccc4)ccc32)cc1
InChIKey: PMIJIUBQPGGGSW-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 catalytic domain incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 49.1 nM (pChEMBL 7.309999942779541)
Descriptors: MW 409.47, ALogP 2.49, HBA 5, HBD 2, PSA 111.26, QED 0.63
Compound (SMILES): Cc1ccc(NC(=O)c2coc3ccccc3c2=O)cc1C
InChIKey: WDCZOLPCRVTBPH-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Non-competitive inhibition of human microsomal MAO-B expressed in recombinant baculovirus infected insect BTI-TN-5B1-4 cells assessed as reduction in H2O2 production using p-tyramine as substrate after 15 mins by Dixon plot method
Measurement: Ki = 0.67 nM (pChEMBL 9.170000076293945)
Descriptors: MW 293.32, ALogP 3.66, HBA 3, HBD 1, PSA 59.31, QED 0.78
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(Cl)c12
InChIKey: CODMIPQTVMYKBE-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 476 nM (pChEMBL 6.320000171661377)
Descriptors: MW 328.76, ALogP 4.04, HBA 5, HBD 1, PSA 76.83, QED 0.56
Compound (SMILES): CC(C)[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2cc(F)c(=O)n(C)c2)c1)c1ccccc1
InChIKey: CFBUFBFJMBWHPM-BJKOFHAPSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Transrepression activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells assessed as inhibition of PMA-stimulated gene expression incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: IC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 512.53, ALogP 4.78, HBA 6, HBD 1, PSA 78.15, QED 0.37
Compound (SMILES): CCCc1nc(C)c2c(=O)[nH]c(-c3cc(-c4ccc(C(=O)NO)cc4)ccc3OCC)nn12
InChIKey: OQSYENMWQGYXMW-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of full length human recombinant N-terminal GST-tagged PDE5A1 expressed in baculovirus infected sf9 cells using cGMP as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 447.5, ALogP 3.53, HBA 7, HBD 3, PSA 121.61, QED 0.29
Compound (SMILES): O=C(Cc1ccc(Cl)c(Cl)c1)N1CCOC2CN(Cc3cccnc3)CC(N3CCCC3)C21
InChIKey: NMHBJNRIZGIDFC-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-Pentazocine from sigma1 receptor in guinea pig brain cortex membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 291 nM (pChEMBL 6.539999961853027)
Descriptors: MW 489.45, ALogP 3.51, HBA 5, HBD 0, PSA 48.91, QED 0.64
Compound (SMILES): Fc1ccc(-c2n[nH]c3c2CCNCC3)cc1
InChIKey: YOZGUJJGVBYZQY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P28222
Assay: Displacement of [3H]LSD from human 5-HT1B receptor expressed in HEK cell membranes after 1.5 hrs by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 231.27, ALogP 1.9, HBA 2, HBD 2, PSA 40.71, QED 0.79
Compound (SMILES): CCCCNc1nc(N)nc2cccc(C(=O)NC(C)C)c12
InChIKey: BEKSUJBQAFPFQK-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 301.39, ALogP 2.56, HBA 5, HBD 3, PSA 92.93, QED 0.71
Compound (SMILES): CNc1nc(Nc2ccc(-n3cnc(C)n3)c(OC)c2)nc2c1CC[C@H]2c1ccc(F)cc1
InChIKey: NDVMOVOEROCRIO-SFHVURJKSA-N
Target: UDP-glucuronosyltransferase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P22309
Assay: Inhibition of human UGT1A1
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 445.5, ALogP 4.38, HBA 8, HBD 2, PSA 89.78, QED 0.46
Compound (SMILES): CC1CCc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCN(C)CC6)cn5)ncc4F)cc3n21
InChIKey: DNURQZGRRIHXKJ-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 490.56, ALogP 4.16, HBA 8, HBD 1, PSA 75, QED 0.45
Compound (SMILES): CC1(C)CCc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCNCC6)cn5)ncc4F)cc3n21
InChIKey: DHPLYCJQWJHXFH-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 490.56, ALogP 4, HBA 8, HBD 2, PSA 83.79, QED 0.44
Compound (SMILES): CC[C@H](NC(=O)C(F)(F)F)[C@H](Oc1ccc(C#N)cc1Br)c1cnc(C2CC2)nc1
InChIKey: XGORDNAQWNGCSW-DOTOQJQBSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Transrepression activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells assessed as inhibition of PMA-stimulated gene expression incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: IC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 483.29, ALogP 4.57, HBA 5, HBD 1, PSA 87.9, QED 0.62
Compound (SMILES): COc1ccccc1[C@]12CO[C@@H](C)C[C@H]1CSC(N)=N2
InChIKey: SPCKMVYZWVCNSY-PGUXBMHVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells for 5 mins at -80 mV holding potential by patch clamp method
Measurement: IC50 = 85600 nM (pChEMBL 4.070000171661377)
Descriptors: MW 292.4, ALogP 2.38, HBA 5, HBD 1, PSA 56.84, QED 0.91
Compound (SMILES): CN1CCN(C2CCN(c3n[nH]c(N)n3)CC2)[C@@H](Cc2ccc(Cl)cc2)C1
InChIKey: BYCLUAVYESDINX-KRWDZBQOSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full-length C-terminal his-tagged human AMCase 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 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 389.94, ALogP 1.87, HBA 6, HBD 2, PSA 77.31, QED 0.83
Compound (SMILES): NS(=O)(=O)c1cccc(/N=C2\NC(=O)/C(=C3/C(=O)N(Cc4ccccc4)c4ccccc43)S2)c1
InChIKey: YHOPAXPQWMGSQU-MRCUWXFGSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human transmembrane carbonic anhydrase 9 by stopped-flow CO2 hydrase assay
Measurement: Ki = 169.8 nM (pChEMBL 6.769999980926514)
Descriptors: MW 490.57, ALogP 3.14, HBA 6, HBD 2, PSA 121.93, QED 0.54
Compound (SMILES): Cc1ccc2c(c1)/C(=C1/S/C(=N/c3ccc(S(N)(=O)=O)cc3)NC1=O)C(=O)N2
InChIKey: WBFWASSTCOJLCZ-PFONDFGASA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human transmembrane carbonic anhydrase 9 by stopped-flow CO2 hydrase assay
Measurement: Ki = 72.1 nM (pChEMBL 7.139999866485596)
Descriptors: MW 414.47, ALogP 1.86, HBA 6, HBD 3, PSA 130.72, QED 0.65
Compound (SMILES): Cc1n[nH]cc1-c1cc2c(s1)C(=O)N[C@]1(CC[C@](O)(C3CCCCC3)CC1)N2
InChIKey: JEMZAKZZKHRMHZ-OYRHEFFESA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of recombinant human Cdk2 (1 to 298 residues)/human N-terminal GST-tagged cyclinE (1 to 410 residues) expressed in baculovirus expression system using histone H1 as substrate after 90 mins in presence of ATP by kinase-glo assay
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 400.55, ALogP 4.18, HBA 5, HBD 4, PSA 90.04, QED 0.61
Compound (SMILES): COC(=O)Cc1ccc(OCc2oc(-c3cccc(OC)c3)nc2C)cc1
InChIKey: GFUKCIXVOZBJQK-UHFFFAOYSA-N
Target: Thyroid hormone receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P10827
Assay: Antagonist activity at CMV-fused TRalpha-LBD-GAL4-DBD (unknown origin) expressed in HEK293T cells assessed as inhibition of T3-induced receptor transactivation after 16 hrs by bright-Glo luciferase reporter gene assay
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 367.4, ALogP 3.95, HBA 6, HBD 0, PSA 70.79, QED 0.59
Compound (SMILES): Cn1cc(Nc2nc(N)nc(-c3cccc(-n4ccc5cc(C6CC6)cc(F)c5c4=O)c3CO)n2)cn1
InChIKey: RQYDQAPLARKISN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of anti-IgM-stimulated BTK phosphorylation at Tyr223 in human Ramos cells pre-incubated for 1 hr followed by anti-IgM stimulation for 10 mins by Western blotting
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 498.52, ALogP 3.41, HBA 10, HBD 3, PSA 136.77, QED 0.32
Compound (SMILES): Cc1ccc(C(=O)c2ccc3c(ccn3Cc3ccc(C(=O)NO)cc3)c2)cc1
InChIKey: WGSFESORDBSYKY-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human HDAC8 using RHKAcKAc peptide as substrate
Measurement: IC50 = 1490 nM (pChEMBL 5.829999923706055)
Descriptors: MW 384.44, ALogP 4.35, HBA 4, HBD 2, PSA 71.33, QED 0.31
Compound (SMILES): CC1(C)CCc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCN(C7CC7)CC6)cn5)ncc4F)cc3n21
InChIKey: FOHJPPOWZXGQDX-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 530.63, ALogP 4.87, HBA 8, HBD 1, PSA 75, QED 0.38
Compound (SMILES): Cc1nc(Nc2ncc(F)c(-c3cc(F)c4nc5n(c4c3)C(C)(C)CC5)n2)ccc1CN1CCNCC1
InChIKey: XBOIHCUWWMWMIZ-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 18700 nM (pChEMBL 4.730000019073486)
Descriptors: MW 504.59, ALogP 4.31, HBA 8, HBD 2, PSA 83.79, QED 0.42
Compound (SMILES): O=C1CCc2c(Oc3ccc4c(c3)[C@H]3[C@@H](O4)[C@@H]3c3nc4ccc(C(F)(F)F)cc4[nH]3)ccnc2N1
InChIKey: NGFFVZQXSRKHBM-YPAWHYETSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant in human A375 cells assessed as reduction in ERK phosphorylation after 1 hr by TR-FRET assay
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 478.43, ALogP 5.3, HBA 5, HBD 2, PSA 89.13, QED 0.42
Compound (SMILES): COC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H]1N=C(c2ccccc2O)S[C@@H]1C
InChIKey: WSMFZWOSGRIXPV-RIEGTJTDSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: Displacement of [3H]-GR65630 from human 5-HT3 receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 388.45, ALogP 1.27, HBA 7, HBD 3, PSA 116.67, QED 0.64
Compound (SMILES): O=C(O)c1noc(-c2ccccc2)c1-c1cccc(-c2cc(Cl)cc(Cl)c2)c1
InChIKey: KFVNPLSZKCTJMO-UHFFFAOYSA-N
Target: Phosphotyrosine-protein phosphatase PTPB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P96830
Assay: Inhibition of Mycobacterium tuberculosis H37Rv His-tagged ptpB H94A mutant expressed in Escherichia coli BL21(DE3) using pNPP as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 410.26, ALogP 6.68, HBA 3, HBD 1, PSA 63.33, QED 0.41
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)Nn2cnc3ccccc32)c(Cl)cc1Cl
InChIKey: AKBIFIJQRGIDLH-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human N-terminal His-tagged carbonic anhydrase 7 (3 to 264 residues) expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 2.23 nM (pChEMBL 8.649999618530273)
Descriptors: MW 385.23, ALogP 2.37, HBA 5, HBD 2, PSA 107.08, QED 0.72
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nnn[nH]3)ccc2N(CC(C)C)CC(C)C)cc1
InChIKey: CJNMMPAEIYFQIJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 497.65, ALogP 6.6, HBA 5, HBD 3, PSA 98.83, QED 0.24
Compound (SMILES): COc1ccccc1N1CCN(CCOCCOc2c(C)cc(C)cc2C)CC1.Cl.Cl
InChIKey: HIGGDBUSQHFDFQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from recombinant human 5-HT1A receptor expressed in HEK293 cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 398.55, ALogP 3.84, HBA 5, HBD 0, PSA 34.17, QED 0.6
Compound (SMILES): CCOC(=O)[C@@H]1CN(CCn2c(=O)[nH]c3ccccc3c2=O)CC[C@@H]1c1ccccc1
InChIKey: GDQOEEGYQOGYPN-UYAOXDASSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Mus musculus
UniProt: Q8BRU6
Assay: Inhibition of VMAT2 in C57Bl/6J mouse striatal membranes assessed as reduction in [3H[-5HT uptake pre-incubated for 10 mins before [3H[-5HT addition and measured after 8 mins
Measurement: IC50 = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 421.5, ALogP 2.36, HBA 6, HBD 1, PSA 84.4, QED 0.62
Compound (SMILES): N=C(N)NC(=O)c1nc(-c2cc3c(F)cccc3o2)c(N2CCCCCC2)nc1N
InChIKey: ITMHCPYYAUUUAC-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using chromogenic L-pyroGlu-L-Pro-L-Arg-p-nitroaniline as substrate by fluorescence assay
Measurement: IC50 = 16700 nM (pChEMBL 4.78000020980835)
Descriptors: MW 411.44, ALogP 2.61, HBA 7, HBD 4, PSA 147.15, QED 0.38
Compound (SMILES): CC1(C)NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: CJCOTNMGGCNQIS-YSLHKSLUSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 825.93, ALogP -1.61, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): COc1ccc(CNC(=O)c2sc3nnc(C)c(C)c3c2N)cc1F
InChIKey: VFNHDIWHQGVWLL-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulator activity at rat M4 receptor expressed in CHO cells co-expressing Gqi5 in presence of EC20 concentration of acetylcholine by calcium mobilization assay
Measurement: EC50 = 26.92 nM (pChEMBL 7.570000171661377)
Descriptors: MW 360.41, ALogP 2.97, HBA 6, HBD 2, PSA 90.13, QED 0.75
Compound (SMILES): Nc1nc(/C=C/CNC(=O)c2cc(Cl)c(Cl)[nH]2)c[nH]1
InChIKey: MYEOSEFRVAPSCL-OWOJBTEDSA-N
Target: Potassium voltage-gated channel subfamily A member 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P22460
Assay: Inhibition of human Kv1.5 expressed in CHO cells at -80 mV holding potential by whole cell automated patch clamp method
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 300.15, ALogP 2.07, HBA 3, HBD 4, PSA 99.59, QED 0.7
Compound (SMILES): CCS(=O)(=O)Nc1cc(-c2ccc3ncnc(Nc4ccc(F)c(Cl)c4)c3c2)cnc1OC
InChIKey: HCDQNNHFLOPNLM-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3K p110delta (unknown origin) using PIP2 as substrate by ELISA
Measurement: IC50 = 8672 nM (pChEMBL 5.059999942779541)
Descriptors: MW 487.94, ALogP 5, HBA 7, HBD 2, PSA 106.1, QED 0.38
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCF)C5)ncc3F)cc2n1C(C)C
InChIKey: GZAGBRPFBCDRDL-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100x, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM x10000 was used as the final data for analysis.
Measurement: IC50 = 22.5 nM (pChEMBL 7.650000095367432)
Descriptors: MW 481.53, ALogP 5.13, HBA 7, HBD 1, PSA 71.76, QED 0.41
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)CC(C)(C)C6)n3)nc2)CC1
InChIKey: WURCEOZSLIZNTF-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 36000 nM (pChEMBL 4.440000057220459)
Descriptors: MW 518.62, ALogP 4.63, HBA 8, HBD 1, PSA 75, QED 0.4
Compound (SMILES): CC(C)[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2ccc(=O)n(C)c2)c1)c1ccccc1
InChIKey: ZQFNDBISEYQVRR-LOSJGSFVSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Antagonist activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells assessed as inhibition of dexamethasone induced transactivation incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 494.54, ALogP 4.64, HBA 6, HBD 1, PSA 78.15, QED 0.39