lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-c3c(C)n[nH]c3C)c12
InChIKey: DBYMHTBRBURFFG-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 = 20.2 nM (pChEMBL 7.699999809265137)
Descriptors: MW 388.43, ALogP 4.4, HBA 6, HBD 2, PSA 105.51, QED 0.47
Compound (SMILES): C[C@@H](CC(=O)O)c1cccc(-n2c(C(N)=O)cc3ccc(OC(F)(F)F)cc32)c1
InChIKey: OSJXLDOVNXZNHD-NSHDSACASA-N
Target: Group 10 secretory phospholipase A2 (SINGLE PROTEIN), Homo sapiens
UniProt: O15496
Assay: Inhibition of recombinant human sPLA2-10 using human HDL as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 406.36, ALogP 4.21, HBA 4, HBD 2, PSA 94.55, QED 0.64
Compound (SMILES): Cl.O=C(NCCCN1CCN(C(c2ccc(F)cc2)c2ccc(F)cc2)CC1)c1ccccn1
InChIKey: NWIWVLFBXCDYPB-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 = 2040 nM (pChEMBL 5.690000057220459)
Descriptors: MW 450.53, ALogP 3.89, HBA 4, HBD 1, PSA 48.47, QED 0.53
Compound (SMILES): C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2cn(-c3ccccc3F)nc2C1)C(F)(F)F
InChIKey: CXIIKZDPYZUXDM-ZDUSSCGKSA-N
Target: Sodium- and chloride-dependent glycine transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y345
Assay: Inhibition of recombinant human GlyT2 expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 497.47, ALogP 3.9, HBA 6, HBD 0, PSA 81.5, QED 0.5
Compound (SMILES): Cc1ccc2[se]c(=S)ccc2c1
InChIKey: QUOKHMNGQWOAHV-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated 15 mins prior to testing by CO2 hydration based stopped-flow assay
Measurement: Ki = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 239.2
Compound (SMILES): CC(C)Cc1ccc(C(C)C(=O)NCCOc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: AKUASIWSLQWUSP-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 = 26.2 nM (pChEMBL 7.579999923706055)
Descriptors: MW 404.53, ALogP 2.83, HBA 4, HBD 2, PSA 98.49, QED 0.63
Compound (SMILES): CC(C(=O)NCCCCOc1ccc(S(N)(=O)=O)cc1)c1cccc(C(=O)c2ccccc2)c1
InChIKey: WCTKEYVDQAIYKK-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 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 480.59, ALogP 3.64, HBA 5, HBD 2, PSA 115.56, QED 0.32
Compound (SMILES): NS(=O)(=O)c1cccc(NC(=[Se])Nc2ccccc2)c1
InChIKey: ZNJCOPMXQMVMNA-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 908.7 nM (pChEMBL 6.039999961853027)
Descriptors: MW 354.29
Compound (SMILES): CC(C)(O)CNC(=O)CC1Cc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N(S(=O)(=O)c2ccc(F)cc2)C1
InChIKey: YACNBOWUNVKVEQ-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR in human HepG2 cells by receptor transactivation assay
Measurement: EC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 586.53, ALogP 3.78, HBA 5, HBD 3, PSA 106.94, QED 0.43
Compound (SMILES): CCN(CC)CC.NC(=O)c1ccc(-c2cc(C(=O)O)cc(-n3cc(-c4ccc(C(F)(F)F)cc4)nn3)c2)cc1
InChIKey: JKXKFAHARWNNMS-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 >= 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 452.39, ALogP 4.42, HBA 5, HBD 2, PSA 111.1, QED 0.47
Compound (SMILES): Cc1nnc2sc(C(=O)N3CC(c4ccccc4)C3)c(N)c2c1C
InChIKey: QOAFWVIRCVXMMQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Positive allosteric modulation of human M3 receptor assessed as increase in acetylcholine-induced response
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 338.44, ALogP 3.13, HBA 5, HBD 1, PSA 72.11, QED 0.78
Compound (SMILES): COC(=O)c1ccc(NC(=O)CSc2nc3ccccc3n2S(=O)(=O)c2cc(C)cc(C)c2)cc1
InChIKey: MYUFPZANAUANOU-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase Y181C mutant in HIV1 infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 > 8360 nM (pChEMBL 5.078000068664551)
Descriptors: MW 509.61, ALogP 4.41, HBA 8, HBD 1, PSA 107.36, QED 0.29
Compound (SMILES): CCCCC/C=C\C/C=C\C/C=C\[C@@H](C)/C=C\CCCC(=O)N[C@H](C)CO
InChIKey: SKCZBQSPGJHKOX-IYXKCDGNSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55,940 from human CB2 receptor expressed in HEK293 cell membranes in absence of FAAH inhibitor PMSF by radioligand binding assay
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 375.6, ALogP 5.88, HBA 2, HBD 2, PSA 49.33, QED 0.26
Compound (SMILES): COC(=O)N1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3n[nH]c(N)n3)CC2)C[C@@H]1C
InChIKey: NZJYXHAPDQHINW-KSSFIOAISA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Human CHIT1 Activity Assay: An enzymatic assay with recombinant human CHIT1 was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-methylumbelliferyl β-D-N,N′,N″-triacetylchitotriose was used as a substrate for the enzyme. Upon hydrolysis by CHIT1, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of CHIT1 recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Solution (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 55000 nM (pChEMBL 4.260000228881836)
Descriptors: MW 447.97, ALogP 2.39, HBA 7, HBD 2, PSA 103.61, QED 0.74
Compound (SMILES): NS(=O)(=O)c1ccc(/N=C2\NC(=O)/C(=C3/C(=O)N(Cc4ccccc4)c4ccc(Cl)cc43)S2)cc1
InChIKey: WOXTYVCOVIDPDA-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 = 90.6 nM (pChEMBL 7.039999961853027)
Descriptors: MW 525.01, ALogP 3.8, HBA 6, HBD 2, PSA 121.93, QED 0.5
Compound (SMILES): O=S(=O)(Oc1ccccc1)C1CC2OC1C(c1ccc(/C=C/c3ccccc3)cc1)=C2c1ccc(O)cc1
InChIKey: VAXQVIZAUTUSJT-VAWYXSNFSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at human ERalpha expressed in HEK293T cells after 24 hrs by ERE-based dual luciferase reporter gene assay
Measurement: IC50 = 1030 nM (pChEMBL 5.989999771118164)
Descriptors: MW 522.62, ALogP 6.42, HBA 5, HBD 1, PSA 72.83, QED 0.22
Compound (SMILES): COc1ccc(NC(=O)N2CCN(c3nc(N)nc4c3cnn4C)[C@@H](C)C2)c(C)c1
InChIKey: WRONAJQPZWDYAR-ZDUSSCGKSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes assessed as decrease in midazolam 1-hydroxylation by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 410.48, ALogP 2.01, HBA 8, HBD 2, PSA 114.43, QED 0.68
Compound (SMILES): CC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CN)C(=O)N[C@@H](CC1CCCC1)C(=O)N1CCC[C@H]1c1nc(-c2ccccc2)cn1CC1CCCCC1)C(C)C
InChIKey: FNDMXKNPADTRQS-ABMZEFHLSA-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 = 101 nM (pChEMBL 7)
Descriptors: MW 886.2, ALogP 4.99, HBA 9, HBD 5, PSA 200.86, QED 0.13
Compound (SMILES): CN(C)C(=O)Cn1ccc2ncc(-c3ccc(Cl)s3)cc21
InChIKey: QRWURIWWBKIGEH-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 319.82, ALogP 3.51, HBA 4, HBD 0, PSA 38.13, QED 0.74
Compound (SMILES): O=C1Nc2ccccc2C12CCN(CCN1CCN(c3cccc(Cl)c3)CC1)C2
InChIKey: FOUPEVPTFDMMLT-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 cell membranes after 1 hr at 37 degC by microbeta scintillation counting analysis
Measurement: Ki = 2005 nM (pChEMBL 5.699999809265137)
Descriptors: MW 410.95, ALogP 3.06, HBA 4, HBD 1, PSA 38.82, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCC2)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: RQCWCCUAQKMWGM-GJOOVXBSSA-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 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 902.03, ALogP 0.08, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): CC(C)S(=O)(=O)c1ccc(O[C@@H](C)C(F)(F)F)c(C(=O)N2Cc3cn(-c4ccccc4)nc3C2)c1
InChIKey: YDEWBMPAQSXMRD-INIZCTEOSA-N
Target: Sodium- and chloride-dependent glycine transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y345
Assay: Inhibition of recombinant human GlyT2 expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 507.53, ALogP 4.54, HBA 6, HBD 0, PSA 81.5, QED 0.49
Compound (SMILES): CNc1ncc2c(-c3ccc(N4CCNCC4)cc3)nn(Cc3cn(Cc4ccccc4)nn3)c2n1
InChIKey: UYWDDAKIGJTMMG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of wild-type human partial length VEGFR2 (R787 to P1253 residues) expressed in mammalian expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 480.58, ALogP 2.63, HBA 10, HBD 2, PSA 101.61, QED 0.37
Compound (SMILES): Oc1ccccc1C1=N[C@@H]2CCC[C@@H]2S1
InChIKey: NPXMBXRWSICWRV-KOLCDFICSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]Ketanserin from 5-HT2A (unknown origin) receptor after 90 mins by microbeta scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 219.31, ALogP 2.81, HBA 3, HBD 1, PSA 32.59, QED 0.79
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccccc2[N+](=O)[O-])n1
InChIKey: NVGNQWINCGJSAT-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 = 6810 nM (pChEMBL 5.170000076293945)
Descriptors: MW 470.92, ALogP 4.33, HBA 9, HBD 1, PSA 105.89, QED 0.4
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H]1Cc2ccc(O)c(c2)CC=CCNCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: FDOGELGBCYXXNJ-ZVOIZXPYSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Agonist activity at Galphaq-Rluc2/Gbeta1/GFP10-Ggamma1 fused human NTS1 expressed in CHO-K1 cell membranes assessed as Galphaq activation after 5 mins by BRET assay
Measurement: EC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 785, ALogP 0.59, HBA 10, HBD 9, PSA 258.31, QED 0.1
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc2ccc([C@H]3CC[C@H](c4ccc5nc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]c5c4)N3c3ccc(OC(F)(F)F)cc3)cc2[nH]1)C(C)C
InChIKey: CSEJJKLTDIYEFX-CTSHUCBISA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HuH7 cell infected HCV genotype 1a H77 assessed as decrease in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.019 nM (pChEMBL 10.720000267028809)
Descriptors: MW 916.02, ALogP 8.51, HBA 10, HBD 4, PSA 187.11, QED 0.09
Compound (SMILES): C=CC(=O)N1CC[C@]2(C1)C[C@H](n1c(NC(=O)c3ccc(-c4cnco4)s3)nc3ccccc31)C2
InChIKey: FINZRTUQZUBKBD-ODAJSGAPSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay
Measurement: IC50 = 0.62 nM (pChEMBL 9.210000038146973)
Descriptors: MW 473.56, ALogP 4.74, HBA 7, HBD 1, PSA 93.26, QED 0.42
Compound (SMILES): CS(=O)(=O)c1ccc(OCC2CC2)c(C(=O)N2Cc3cn(-c4ccccc4F)nc3C2)c1
InChIKey: QTCZENNLHAHFPC-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent glycine transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y345
Assay: Inhibition of recombinant human GlyT2 expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 455.51, ALogP 3.36, HBA 6, HBD 0, PSA 81.5, QED 0.57
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc3c(cc12)C(C)OCC(CO)N3S(C)(=O)=O
InChIKey: JOVIWIQLADFGSH-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 3a NS5B polymerase infected in human HuH7 replicon cells by luciferase reporter gene assay
Measurement: EC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 462.5, ALogP 2.82, HBA 6, HBD 2, PSA 109.08, QED 0.62
Compound (SMILES): Fc1cccc(-n2cnc3c(NCc4nc5c(F)c(F)ccc5[nH]4)nc(N4CCOCC4)nc32)c1
InChIKey: CEBMEQPREMCWOL-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/Cyclin D1 (unknown origin)
Measurement: IC50 = 428 nM (pChEMBL 6.369999885559082)
Descriptors: MW 480.45, ALogP 3.56, HBA 8, HBD 2, PSA 96.78, QED 0.4
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)C(C)(C)CC6)n3)nc2C)CC1
InChIKey: DHQOXLRGBCLMFX-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 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 532.64, ALogP 5.04, HBA 8, HBD 1, PSA 75, QED 0.37
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-c3c[nH]c4ccc(F)cc34)c12
InChIKey: NNMBACIOOKWMKW-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 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 427.44, ALogP 5.68, HBA 5, HBD 2, PSA 92.62, QED 0.38
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)Cn2ccnc2)c(Cl)cc1Cl
InChIKey: VMDQSCJPYHQIPE-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) in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 334.18, ALogP 1.72, HBA 5, HBD 1, PSA 95.05, QED 0.86
Compound (SMILES): CNc1ncc2c(-c3ccc(OC)cc3)nn(CC3OCCO3)c2n1
InChIKey: HCOCLLJWSDTXOM-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of wild-type human partial length FLT3 (V592 to Y969 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 341.37, ALogP 1.92, HBA 8, HBD 1, PSA 83.32, QED 0.76
Compound (SMILES): c1cnc2c(c1)CC[C@@H]1CNCCN21
InChIKey: NDVQTLLBHWRZQL-SNVBAGLBSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at 5-HT2CR (unknown origin) transfected in human HEK293 cells by IP3 accumulation assay
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 189.26, ALogP 0.81, HBA 3, HBD 1, PSA 28.16, QED 0.65
Compound (SMILES): CC(=O)Nc1cc(Nc2nc(-c3cccc(C(F)(F)F)n3)nc3[nH]ccc23)ccn1
InChIKey: HCZOMSNBQCWQJO-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Biological Assays: Assays are conducted in 1536-well plates and 2 mL reactions are prepared from addition of HIS-TGFβR1 T204D or HIS-TGFβR2 WT, anti-HIS detection antibody, a labeled small molecule probe (Kd=<100 nM; koff=<0.001 s−1.) and test compounds in assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35, 4 mM DTT, and 0.05 mg/ml BSA). The reaction is incubated for 1 hour at room temperature and the HTRF signal was measured on an Envision plate reader (Ex: 340 nm; Em: 520 nm/495 nm). Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assay are 1 nM HIS-TGFβR1 T204D or HIS-TGFβR2 WT, 0.2 nM anti-HIS detection antibody, labeled small molecule probe (at Kd) and 0.5% DMSO. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 0.67 nM (pChEMBL 9.170000076293945)
Descriptors: MW 413.36, ALogP 4.14, HBA 6, HBD 3, PSA 108.48, QED 0.46
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](C)N)C(=O)N[C@@H](Cc2ccc(-c3ccccc3)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1)C(=O)O
InChIKey: WCEAINQCXPGEMW-ZMTHPLQNSA-N
Target: Urotensin-2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKP6
Assay: Displacement of [Na125I]-synthetic URP from human UT receptor expressed in HEK293 cell membranes incubated for 2 hrs by gamma-counting
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1093.34
Compound (SMILES): CCCCNc1nc(N)nc2cccc(OCc3ccccc3)c12
InChIKey: HGBKVZNAKQCXAK-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 322.41, ALogP 4, HBA 5, HBD 2, PSA 73.06, QED 0.64
Compound (SMILES): Nc1nc2[nH]c(CCCCc3cccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)n3)cc2c(=O)[nH]1
InChIKey: MOXHYHJYCFVSLZ-HNNXBMFYSA-N
Target: Folate receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P14207
Assay: Binding affinity to human FR-beta receptor expressed in Chinese hamster D4 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs in presence of folic acid by Cell-Titer Blue assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.46, ALogP 0.84, HBA 7, HBD 6, PSA 204.15, QED 0.23
Compound (SMILES): CCS(=O)(=O)c1ccc(O[C@@H](C)C(F)(F)F)c(C(=O)N2Cc3cn(-c4ccccc4F)nc3C2)c1
InChIKey: CQRYWERSRKWMMT-AWEZNQCLSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.5, ALogP 4.29, HBA 6, HBD 0, PSA 81.5, QED 0.46
Compound (SMILES): CCC(=C(c1ccc(OCCN2CCCCCC2)cc1)c1ccc(OCCN2CCCCCC2)cc1)c1cccc(C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)NCC(N)=O)c1
InChIKey: LWAKAHVTROSPCV-BSNUEQINSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of trypsin-like activity of human 26S proteasome using Boc-LRR-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 = 32000 nM (pChEMBL 4.5)
Descriptors: MW 1234.6
Compound (SMILES): COc1ccccc1N1CCN(CCCOc2ccc(C)cc2C)CC1.Cl
InChIKey: KLUFPWHPNQQEIE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from recombinant human 5-HT2A receptor expressed in HEK293 cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki = 527 nM (pChEMBL 6.28000020980835)
Descriptors: MW 354.49, ALogP 3.9, HBA 4, HBD 0, PSA 24.94, QED 0.7
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCCC2)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: IMHRKTSTOJYVSH-UBLLTGQXSA-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 866, ALogP -0.69, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): Oc1ccccc1C1=NC(Cc2c[nH]cn2)C(c2ccccc2)S1
InChIKey: BDLSNMGOWYNTSL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-Mesulergine from human 5-HT2C receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 335.43, ALogP 3.96, HBA 4, HBD 2, PSA 61.27, QED 0.76
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4ccc5nc6n(c5c4)C(C)(C)CC6)n3)nc2)CC1
InChIKey: JLIDFAZKTWWWCN-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 = 15800 nM (pChEMBL 4.800000190734863)
Descriptors: MW 500.63, ALogP 4.59, HBA 8, HBD 1, PSA 75, QED 0.42
Compound (SMILES): CNC(=O)c1cc(OCCCCN2CCC(c3noc4cc(F)ccc34)CC2)ccn1
InChIKey: UWPUFUJRTFJLEP-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Antagonistic activity at histamine 1 receptor (unknown origin) after 10 mins by FLIPR assay
Measurement: IC50 = 4420 nM (pChEMBL 5.360000133514404)
Descriptors: MW 426.49, ALogP 3.76, HBA 6, HBD 1, PSA 80.49, QED 0.55
Compound (SMILES): CNc1ncc2c(-c3ccc(N4CCNCC4)nc3)nn(Cc3cn(Cc4ccccc4)nn3)c2n1
InChIKey: USPKFTCYXHJXCN-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of wild-type human partial length FLT3 (V592 to Y969 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 481.57, ALogP 2.03, HBA 11, HBD 2, PSA 114.5, QED 0.36
Compound (SMILES): C[C@H](Oc1ccc(C#N)cc1C(=O)N1Cc2cn(C3CCCC3)nc2C1)C(F)(F)F
InChIKey: DSCZITNNZITYPG-ZDUSSCGKSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.42, ALogP 4.36, HBA 5, HBD 0, PSA 71.15, QED 0.74
Compound (SMILES): COc1cc2c(cc1OC)Nc1ncnc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)c1NC2
InChIKey: BWXISLRRARTIGU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 = 267.6 nM (pChEMBL 6.570000171661377)
Descriptors: MW 588.57, ALogP 5.59, HBA 9, HBD 4, PSA 135.73, QED 0.19
Compound (SMILES): COc1ccc(C(=O)c2ccc3c(ccn3Cc3ccc(/C=C/C(=O)NO)cc3)c2)cc1
InChIKey: GCPBYJXMWMXUHJ-AWNIVKPZSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using RHKKAc peptide as substrate
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 426.47, ALogP 4.45, HBA 5, HBD 2, PSA 80.56, QED 0.2
Compound (SMILES): O=c1c2cn(C3COC3)nc2nc(SCc2cccc(F)c2)n1-c1ccccc1
InChIKey: IBYYWHNJSYBLSJ-UHFFFAOYSA-N
Target: Retinaldehyde dehydrogenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P47895
Assay: Inhibition of ALDH1A3 in human OVCAR5 cells assessed as reduction in aldefluor positive cells incubated for 30 mins by aldefluor assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 408.46, ALogP 3.58, HBA 7, HBD 0, PSA 61.94, QED 0.37
Compound (SMILES): CCOc1cc(/C=C/C(=O)c2ccncc2)cc(OC)c1OCC
InChIKey: SQZFPRBIMUDDBG-VOTSOKGWSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in yeast microsomal membranes using dibenzylfluorescein as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 327.38, ALogP 3.78, HBA 5, HBD 0, PSA 57.65, QED 0.55
Compound (SMILES): C[C@]12CC[C@H](O)CC1=C(C(N)=O)C[C@@H]1[C@@H]2CC[C@]2(C)C(c3cccnc3)=CC[C@@H]12
InChIKey: CPGOQTKJUPLDPD-ACAUBTHISA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of C-terminal His-tagged recombinant human CYP17A1delta19H mutant expressed in Escherichia coli DH5alpha assessed as decrease in progesterone hydroxylation preincubated for 3 mins followed by NADPH addition measured after 10 mins in presence of cytochrome p450 reductase by LC-MS/MS method
Measurement: IC50 = 22.8 nM (pChEMBL 7.639999866485596)
Descriptors: MW 392.54, ALogP 4.25, HBA 3, HBD 2, PSA 76.21, QED 0.79
Compound (SMILES): O=C(Cc1ccc(Cl)cc1)Nc1cccc(-c2cccc(N3CCCC3)c2)c1
InChIKey: SKRNGXUJIZSKLC-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Positive allosteric modulation of human CB1 receptor expressed in CHO-K1 cell membranes assessed as induction of [3H]CP55,940 binding after 1.5 hrs by liquid scintillation counting assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 390.91, ALogP 5.79, HBA 2, HBD 1, PSA 32.34, QED 0.6
Compound (SMILES): COC(=O)Cc1ccc(OCc2oc(-c3ccccc3OC)nc2C)cc1
InChIKey: GWVLKHYLZIYXAO-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Antagonist activity at CMV-fused RXRalpha-LBD-GAL4-DBD (unknown origin) expressed in HEK293T cells assessed as inhibition of bexarotene-induced receptor transactivation after 16 hrs by bright-Glo luciferase reporter gene assay
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 367.4, ALogP 3.95, HBA 6, HBD 0, PSA 70.79, QED 0.59
Compound (SMILES): C=CC(=O)Nc1ccccc1Oc1nc(Nc2ccc(N3CCN(C)CC3)cc2OC)ncc1Cl
InChIKey: BUSXEFVPHHJABW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL T315I mutant in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 2370 nM (pChEMBL 5.619999885559082)
Descriptors: MW 494.98, ALogP 4.55, HBA 8, HBD 2, PSA 91.85, QED 0.44
Compound (SMILES): Cc1cccc(-c2nc(Nc3ccncc3F)c3cc[nH]c3n2)n1
InChIKey: GAWGUDTUQRRPQK-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Biological Assays: Assays are conducted in 1536-well plates and 2 mL reactions are prepared from addition of HIS-TGFβR1 T204D or HIS-TGFβR2 WT, anti-HIS detection antibody, a labeled small molecule probe (Kd=<100 nM; koff=<0.001 s−1.) and test compounds in assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35, 4 mM DTT, and 0.05 mg/ml BSA). The reaction is incubated for 1 hour at room temperature and the HTRF signal was measured on an Envision plate reader (Ex: 340 nm; Em: 520 nm/495 nm). Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assay are 1 nM HIS-TGFβR1 T204D or HIS-TGFβR2 WT, 0.2 nM anti-HIS detection antibody, labeled small molecule probe (at Kd) and 0.5% DMSO. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 320.33, ALogP 3.61, HBA 5, HBD 2, PSA 79.38, QED 0.6
Compound (SMILES): c1ccc(Cn2nnc3c(Sc4nc5ccccc5o4)ncnc32)cc1
InChIKey: HZSOKHVVANONPV-UHFFFAOYSA-N
Target: NADPH oxidase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PH1
Assay: Inhibition of human NOX5 transfected in HEK cells assessed as PMA-induced hydrogen peroxide production pre-incubated for 10 mins and measured after 15 mins by Amplex-res based fluorescence assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 360.4, ALogP 3.56, HBA 8, HBD 0, PSA 82.52, QED 0.45
Compound (SMILES): CS(=O)(=O)c1ccc(N2CCC(F)(F)CC2)c(C(=O)N2Cc3cn(-c4cncc(F)c4)nc3C2)c1
InChIKey: GIRFLANIOVOTNP-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 505.52, ALogP 3.2, HBA 7, HBD 0, PSA 88.4, QED 0.54
Compound (SMILES): CCC(=C(c1ccc(OCCN2CCCCCC2)cc1)c1ccc(OCCN2CCCCCC2)cc1)c1cccc(C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)NCC(=O)NCC(N)=O)C(C)C)c1
InChIKey: MSKAIELHPGTGHE-MCHZRRGRSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of trypsin-like activity of human 26S proteasome using Boc-LRR-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 1269.64
Compound (SMILES): CC(=O)N1c2ccc(-c3ccsc3)cc2[C@H](NC(=O)OC(C)C)C[C@@H]1C
InChIKey: VDHPCDUFNMXSRQ-SCLBCKFNSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to BRD2 bromodomain 1 (74 to 194 residues) (unknown origin) by ITC
Measurement: Kd = 71.65 nM (pChEMBL 7.139999866485596)
Descriptors: MW 372.49, ALogP 4.74, HBA 4, HBD 1, PSA 58.64, QED 0.85
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C
InChIKey: JRIVTLCAZKSBNE-XSTSSERXSA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Displacement of N-Flu-DOT1L from MBP-tagged AF9 (unknown origin) (487 to 568 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 807.05, ALogP 0.29, HBA 9, HBD 6, PSA 226.66, QED 0.1
Compound (SMILES): C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2cn(-c3ccccc3)nc2C1)C(F)(F)F
InChIKey: FLOKUNMZCPFDCT-AWEZNQCLSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.48, ALogP 3.76, HBA 6, HBD 0, PSA 81.5, QED 0.56
Compound (SMILES): C[C@H](Oc1ccc(C#N)cc1C(=O)N1Cc2cn(-c3ccccc3F)nc2C1)C(F)(F)F
InChIKey: VKGADGOKBFTLBI-ZDUSSCGKSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 444.39, ALogP 4.37, HBA 5, HBD 0, PSA 71.15, QED 0.56
Compound (SMILES): Nc1nc(/C=C/CNC(=O)c2cc3cc(Cl)ccc3[nH]2)c[nH]1
InChIKey: KZGCMSHMRDZXCJ-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 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 315.76, ALogP 2.57, HBA 3, HBD 4, PSA 99.59, QED 0.6
Compound (SMILES): CCOC(=O)c1c(C)oc2cc(OCCc3ccccc3)c(OCc3oc4cc(OC)c(OS(=O)(=O)[O-])cc4c3C(=O)OCC)cc12.[Na+]
InChIKey: UKKMFJZHHXIETC-UHFFFAOYSA-M
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using spectrozyme TH as substrate pretreated for 10 mins followed by substrate addition measured in presence of 5 uM exosite 1 competitor hirudine peptide by spectrophotometric method
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 668.67, ALogP 6.23, HBA 12, HBD 1, PSA 170.17, QED 0.1
Compound (SMILES): CC1(C)CCc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCN(CCF)CC6)cn5)ncc4F)cc3n21
InChIKey: PYAFOBDKPDBAIO-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 = 11200 nM (pChEMBL 4.949999809265137)
Descriptors: MW 536.61, ALogP 4.68, HBA 8, HBD 1, PSA 75, QED 0.37
Compound (SMILES): COc1ccc(Cn2cc(C(=O)NCCCNc3c4c(nc5cc(Cl)ccc35)CCCC4)c(=O)c3ccccc32)cc1
InChIKey: MXLDMFKZOSQDCE-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Mixed type inhibition of human erythrocyte AChE assessed as enzyme-substrate-inhibitor complex using varying levels of acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Lineweaver-Burk plot analysis
Measurement: Ki = 1.57 nM (pChEMBL 8.800000190734863)
Descriptors: MW 581.12, ALogP 6.37, HBA 6, HBD 2, PSA 85.25, QED 0.2
Compound (SMILES): CCCCNc1nc(N)nc2cccc(C(=O)NC)c12
InChIKey: GVIUZMOSJDBOBT-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 273.34, ALogP 1.78, HBA 5, HBD 3, PSA 92.93, QED 0.72
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2cccc(N)c2)n1
InChIKey: AFYVDDVXNBWDRP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL T315I mutant in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 1960 nM (pChEMBL 5.710000038146973)
Descriptors: MW 440.94, ALogP 4.01, HBA 8, HBD 2, PSA 88.77, QED 0.56
Compound (SMILES): Cc1cc2ncn(CC(=O)c3cc(S(N)(=O)=O)c(Cl)cc3Cl)c2cc1C
InChIKey: KQWDYZRSOUJMMK-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 = 12.8 nM (pChEMBL 7.889999866485596)
Descriptors: MW 412.3, ALogP 3.49, HBA 5, HBD 1, PSA 95.05, QED 0.66
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H]1Cc2ccc(O)c(c2)CC=CCNCCCC[C@@H](N)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: DVNLPYWUFMLUBP-DVNNJGNOSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]Tyr3-neurotensin from human NTS1 receptor expressed in CHOK1 cell membranes after 60 mins by gamma counting analysis
Measurement: Ki = 772 nM (pChEMBL 6.110000133514404)
Descriptors: MW 813.05, ALogP 1.37, HBA 10, HBD 9, PSA 258.31, QED 0.1
Compound (SMILES): CC(C)c1n[nH]c2c(NCc3ccccc3)nc(NC3CCCCC3N)nc12
InChIKey: NVTINYQXFHNHIJ-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CDK6 (M1 to A326 residues)/CyclinD1 (Q4 to I295 residues) expressed in Sf9 insect cells
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 379.51, ALogP 3.77, HBA 6, HBD 4, PSA 104.54, QED 0.52
Compound (SMILES): O=C(/C=C/c1ccc2c(c1)OCO2)c1ccncc1
InChIKey: GPOGQKDGSULXOE-HNQUOIGGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in yeast microsomal membranes using dibenzylfluorescein as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 253.26, ALogP 2.71, HBA 4, HBD 0, PSA 48.42, QED 0.62
Compound (SMILES): Cc1ccc(-c2n[nH]c3c2CCNCC3)cc1
InChIKey: LWNZEHWQIHUHGP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: Displacement of [3H]LSD from human 5-HT1D receptor expressed in HEK cell membranes after 1.5 hrs by microbeta scintillation counting method
Measurement: Ki = 165 nM (pChEMBL 6.78000020980835)
Descriptors: MW 227.31, ALogP 2.07, HBA 2, HBD 2, PSA 40.71, QED 0.78
Compound (SMILES): CC[C@](C)(NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@H](CO)NC(=O)c1c[nH]cn1)C(=O)N[C@@H](Cc1ccncc1)C(=O)N[C@@H](CC1CCCCC1)C(=O)N[C@@H](CC(C)(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NC(C)(C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1CCCCC1)C(N)=O)[C@@H](C)O
InChIKey: XSWVCJPBSYFGDH-SGUWVVKZSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63447
Assay: Agonist activity at rat neuropeptide Y4 receptor by [35S]GTPgammaS binding assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1861.23
Compound (SMILES): C[C@@H]1SC(c2cc3ccccc3cc2O)=N[C@H]1CO
InChIKey: OHKDLICNPQPHJS-ZANVPECISA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor expressed in HEK cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 810 nM (pChEMBL 6.090000152587891)
Descriptors: MW 273.36, ALogP 2.79, HBA 4, HBD 2, PSA 52.82, QED 0.88
Compound (SMILES): O=S(=O)(c1ccc(F)cc1)N1CCSc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc21
InChIKey: NMKUHNALTSCROZ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at Gal4-tagged human RORbeta ligand binding domain expressed in human Jurkat cells by native IL17 promoter driven luciferase reporter gene assay
Measurement: EC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 475.41, ALogP 4.44, HBA 4, HBD 1, PSA 57.61, QED 0.67
Compound (SMILES): O=C1C(c2ccccc2)N(S(=O)(=O)c2ccc(Cl)cc2)C(=O)C(c2ccccc2)N1S(=O)(=O)c1ccc(Cl)cc1
InChIKey: AWDIEUWPIRIVDC-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Competitive inhibition of human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH as substrate preincubated for 60 mins followed by substrate addition by secondary plot analysis
Measurement: Ki = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 615.52, ALogP 5.22, HBA 6, HBD 0, PSA 108.9, QED 0.29
Compound (SMILES): Cl.N[C@@H]1CCC=C(c2ccc(F)cc2)[C@H]1CNc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl
InChIKey: BBOCDUNYRYILGP-LJLRIERRSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan 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 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 511.02, ALogP 5.11, HBA 6, HBD 3, PSA 97.11, QED 0.41
Compound (SMILES): Cn1cnc(-c2cnc(O[C@H]3CCN(C(=O)Cc4ccc(OC(F)(F)F)cc4)C[C@H]3F)c(C(N)=O)c2)c1
InChIKey: XJIIVPVOGYFVME-QUCCMNQESA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR (unknown origin) by cell based assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 521.47, ALogP 3.04, HBA 7, HBD 1, PSA 112.57, QED 0.48
Compound (SMILES): COc1cccc(C(=O)c2ccc3c(ccn3Cc3ccc(C(=O)NO)cc3)c2)c1
InChIKey: JUCXGZCQWAXAJZ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using RHKKAc peptide as substrate
Measurement: IC50 = 16.4 nM (pChEMBL 7.789999961853027)
Descriptors: MW 400.43, ALogP 4.05, HBA 5, HBD 2, PSA 80.56, QED 0.29
Compound (SMILES): CCc1nn2c(C)cc(C)nc2c1Cc1ccc(/C=C/CN2CCNC(=O)C2)cc1
InChIKey: RCLGGYHTKGHRBY-AATRIKPKSA-N
Target: G-prodeshotein coupled receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P46093
Assay: Antagonist activity at human GPR4 expressed in human HeLa cells assessed as inhibition of IBMX-induced cAMP accumulation after 15 mins by HTRF assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 403.53, ALogP 2.94, HBA 5, HBD 1, PSA 62.53, QED 0.69
Compound (SMILES): CC(C)(C)Cn1ncn(-c2ccc(C(F)(F)C(O)(Cn3cnnn3)c3ccc(F)cc3F)nc2)c1=O
InChIKey: RLVSHXDYKHPCOY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated for 10 mins with substrate followed by NADPH addition measured after 15 mins by LC/MS/MS analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 506.46, ALogP 2.42, HBA 10, HBD 1, PSA 116.54, QED 0.38
Compound (SMILES): C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2cn(-c3ccccc3F)nc2C1)C(F)(F)F
InChIKey: CXIIKZDPYZUXDM-ZDUSSCGKSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 497.47, ALogP 3.9, HBA 6, HBD 0, PSA 81.5, QED 0.5
Compound (SMILES): CC(C)Cc1ccc(C(C)C(=O)NCCOc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: AKUASIWSLQWUSP-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 404.53, ALogP 2.83, HBA 4, HBD 2, PSA 98.49, QED 0.63
Compound (SMILES): CC(C(=O)NCCCCOc1ccc(S(N)(=O)=O)cc1)c1cccc(C(=O)c2ccccc2)c1
InChIKey: WCTKEYVDQAIYKK-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 480.59, ALogP 3.64, HBA 5, HBD 2, PSA 115.56, QED 0.32