lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3ncccc3C#N)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: HENRITOGWFFGGA-PMACEKPBSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 in human Jurkat cells assessed as inhibition of SLP76 phosphorylation by measuring inhibition constant incubated for 1 hr by HTRF assay
Measurement: Ki = 232 nM (pChEMBL 6.630000114440918)
Descriptors: MW 539.57, ALogP 3.38, HBA 9, HBD 3, PSA 150.28, QED 0.32
Compound (SMILES): Fc1cccc(F)c1-c1ccncc1CN1C(c2ccco2)=NO[C@@H]1c1cc(C(F)(F)F)cc(C(F)(F)F)c1Cl
InChIKey: NCOAFQYMHNPHON-XMMPIXPASA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q80SS6
Assay: Agonist activity at mouse TGR5 receptor
Measurement: EC50 = 249 nM (pChEMBL 6.599999904632568)
Descriptors: MW 587.85, ALogP 8.2, HBA 5, HBD 0, PSA 50.86, QED 0.22
Compound (SMILES): COc1ccc(CNCCCCCCC(=O)NO)cc1OC
InChIKey: IQGSZEFWMXKAJG-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human recombinant HDAC2 expressed in baculovirus by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 310.39, ALogP 2.25, HBA 5, HBD 3, PSA 79.82, QED 0.33
Compound (SMILES): CC(C)C[C@H](NC(=O)CCCCCNC(=O)c1ccc(C(=O)O)c(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)(C)C)C(=O)N[C@@H](C(C)C)P(=O)(Oc1ccccc1)Oc1ccccc1
InChIKey: WLOUMDSRFSCFPJ-WKIKYWDLSA-N
Target: Serine protease HTRA2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O43464
Assay: Inhibition of recombinant human HTRA2 using H2-OPT as substrate assessed as increase in fluorescence and measured for 2 hrs by fluorescent plate reader analysis
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 1164.3
Compound (SMILES): O=C(Nc1cnccc1Oc1ccccc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: QORWUQJNIZUKNZ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition of GST tagged GSK-3alpha (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 374.4, ALogP 3.87, HBA 5, HBD 2, PSA 93.21, QED 0.68
Compound (SMILES): CCCCC(C)(O)c1cc(C(=O)N2Cc3ccccc3C2)ccc1O
InChIKey: UCYLZAFLPPNBDX-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P08238
Assay: Binding affinity to HSP90beta (unknown origin)
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 339.44, ALogP 3.95, HBA 3, HBD 2, PSA 60.77, QED 0.87
Compound (SMILES): O=C(Cc1ccccc1)N1CCN(c2ccc(O)cc2)CC1
InChIKey: VEAAIEOUCDGSDL-UHFFFAOYSA-N
Target: NAD-dependent malic enzyme, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P23368
Assay: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 296.37, ALogP 2.28, HBA 3, HBD 1, PSA 43.78, QED 0.94
Compound (SMILES): COC[C@@H](NC(=O)C1(OC)CCCCC1)C(=O)Nc1nnc(Cc2ccc(C#N)cc2)s1
InChIKey: KZCFYGAZZFIEGY-QGZVFWFLSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 21 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UK80
Assay: Inhibition of human USP21 using ubiquitin rhodamine 110 110 as substrate preincubated for 15 to 20 mins followed by enzyme addition and measured after 25 mins by fluorometric assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 457.56, ALogP 2.42, HBA 8, HBD 2, PSA 126.23, QED 0.59
Compound (SMILES): Nc1ncc(-c2cc(N3C[C@@H]4C[C@H]3CO4)nc(N3CC4CC3C4)n2)nc1C(F)(F)F
InChIKey: QUJWSXIGZUDUAB-QQFIATSDSA-N
Target: Mitogen-activated protein kinase kinase kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: O43283
Assay: Inhibition of recombinant N-terminal GST-tagged human LZK (9 to 114 residues) expressed in Sf21 cells assessed as reduction in substrate phosphorylation using MKK4 and ATP as substrate incubated for 1.5 hrs by HTRF analysis
Measurement: IC50 = 149 nM (pChEMBL 6.829999923706055)
Descriptors: MW 419.41, ALogP 2.11, HBA 8, HBD 1, PSA 93.29, QED 0.81
Compound (SMILES): Cc1cc2c(=O)[nH]c(-c3ccc(C(C)(C)O)cc3)cn2n1
InChIKey: HJVQHFYHONMFDN-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of TNKS2 (unknown origin) using biotinylated NAD as substrate assessed as inhibition of autoPARsylation activity incubated for 1 hr by ELISA
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 283.33, ALogP 2.23, HBA 4, HBD 2, PSA 70.39, QED 0.76
Compound (SMILES): CC1CN(C)C(=O)CN1c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: PTGSNZODFVWKQQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of recombinant human wild type FGFR1 (399 to 820 residues) using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by HTRF assay
Measurement: IC50 = 1214 nM (pChEMBL 5.920000076293945)
Descriptors: MW 326.36, ALogP 0.42, HBA 7, HBD 1, PSA 95.83, QED 0.73
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](CN(CC[C@H](N)C(=O)O)S(=O)(=O)c2cnc(Cl)cn2)[C@@H](O)[C@H]1O
InChIKey: NUFHSMQFUWVWAB-ACSHICKMSA-N
Target: tRNA (cytosine(38)-C(5))-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: O14717
Assay: Displacement of FTAD from full-length human DNMT2 expressed in bacteria incubated for 10 mins by MST assay
Measurement: Kd = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 543.95, ALogP -2.04, HBA 14, HBD 5, PSA 245.79, QED 0.2
Compound (SMILES): N#CC(c1ccc(F)cc1)c1cccc(C(F)(F)F)n1
InChIKey: DXQNDKQUHKVTTC-UHFFFAOYSA-N
Target: Acyl-homoserine lactone acylase PvdQ (SINGLE PROTEIN), Pseudomonas aeruginosa (strain LESB58)
UniProt: Q9I194
Assay: Inhibition of wild type Pseudomonas aeruginosa PAO1 pvdQ
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 280.22, ALogP 3.89, HBA 2, HBD 0, PSA 36.68, QED 0.78
Compound (SMILES): O=C(Nc1ccc2[nH]ncc2c1)c1csc(Nc2ccccc2)n1
InChIKey: CYVGSDYVNUNREA-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human CK1epsilon expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 335.39, ALogP 4.02, HBA 5, HBD 3, PSA 82.7, QED 0.53
Compound (SMILES): CN(C)c1ccc2c(c1)C(=O)N(c1ccc3ccn(CCCCN4CCC5(CC4)OCc4ccccc45)c3c1)C2=O
InChIKey: YNRCGCRRNOTJIA-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma 2 receptor in Wistar Han rat liver membrane assessed as inhibition constant incubated for 120 mins
Measurement: Ki = 5.07 nM (pChEMBL 8.289999961853027)
Descriptors: MW 548.69, ALogP 5.81, HBA 6, HBD 0, PSA 58.02, QED 0.22
Compound (SMILES): CCC[C@H](C)Oc1ccc(C(C)(C)C)cc1NC(=O)c1nnn(-c2cc(OC)ccc2OC)c1C
InChIKey: LCZDEXFSZLWZDC-KRWDZBQOSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Inverse agonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition of receptor basal activity incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 480.61, ALogP 5.71, HBA 7, HBD 1, PSA 87.5, QED 0.42
Compound (SMILES): O=C1OC(c2ccccc2)CN1c1ccc(-c2n[nH]c(=O)c3ccccc23)cc1
InChIKey: XBFKWPJSFZZRIG-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of ROCK2 (unknown origin)
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 383.41, ALogP 4.29, HBA 4, HBD 1, PSA 75.29, QED 0.57
Compound (SMILES): CC(C)n1c2c(=O)c(-c3ccccc3)cc(=O)c2c2c(=O)c3ccccc3c21
InChIKey: UZVZYKXLYYJYSO-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P30307
Assay: Inhibition of CDC25C (unknown origin)
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 367.4, ALogP 4.15, HBA 4, HBD 0, PSA 56.14, QED 0.47
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CC4)c3)c2n1
InChIKey: HBAQYPYDRFILMT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of recombinant human wild type FGFR1 (399 to 820 residues) using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by HTRF assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 364.41, ALogP 1.36, HBA 7, HBD 1, PSA 95.83, QED 0.75
Compound (SMILES): CCCCCCNNC(=O)c1ccc(Br)cc1
InChIKey: YQIPSZXUSOVGKH-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 10270 nM (pChEMBL 4.989999771118164)
Descriptors: MW 299.21, ALogP 3.26, HBA 2, HBD 2, PSA 41.13, QED 0.6
Compound (SMILES): c1cncc(C[C@@H]2[C@@H](Oc3ccc(-c4ccc[nH]4)nn3)C3CCN2CC3)c1
InChIKey: ZKWHETNMJXBGTO-CTNGQTDRSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Binding affinity to alpha4beta2 nAChR (unknown origin) assessed as dissociation constant
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 361.45, ALogP 2.95, HBA 5, HBD 1, PSA 66.93, QED 0.76
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ncccn1
InChIKey: GQFVXGULVTUNMM-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of TNF-alpha induced NF-kappaB signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 472.95, ALogP 3.84, HBA 6, HBD 1, PSA 101.49, QED 0.6
Compound (SMILES): Cc1ccncc1-c1cccc2c(-c3ccccc3)cnn12
InChIKey: OEASNOILUJUFML-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 285.35, ALogP 4.37, HBA 3, HBD 0, PSA 30.19, QED 0.55
Compound (SMILES): CCCCOc1ccc(CCC(=O)N2CCN(c3ccc(O)cc3)CC2)cc1
InChIKey: ANKCAVFAEXIRFY-UHFFFAOYSA-N
Target: NAD-dependent malic enzyme, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P23368
Assay: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 382.5, ALogP 3.85, HBA 4, HBD 1, PSA 53.01, QED 0.7
Compound (SMILES): CC1(C)CN(C(N)=O)c2cccc(Cl)c2N1Cc1ccccc1
InChIKey: LFFJNNHFVVGWIU-UHFFFAOYSA-N
Target: AMP deaminase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q01433
Assay: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 329.83, ALogP 4.02, HBA 2, HBD 1, PSA 49.57, QED 0.9
Compound (SMILES): CCN1CCN(Cc2cc(Nc3ncc(C(=O)Nc4ccccc4N)s3)nc(C)n2)CC1
InChIKey: JXYHYYBXKLTNGG-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of full length human recombinant HDAC1 using AcLys-Tyr-Lys(e-acetyl)-AMC as substrate incubated for 24 hrs
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 452.59, ALogP 2.96, HBA 9, HBD 3, PSA 112.3, QED 0.47
Compound (SMILES): COc1ccc(Nc2ncnc3c2cnn3-c2ccc(Cl)cc2C)cc1Cl
InChIKey: RNJQSVZFLIHBSM-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant PI5P4Kgamma (unknown origin) expressed in Escherichia coli BL21(DE3) by ADP-Glo reagent based assay
Measurement: IC50 > 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 400.27, ALogP 5.18, HBA 6, HBD 1, PSA 64.86, QED 0.51
Compound (SMILES): CC1(C)CN(C(N)=O)c2c(F)cccc2N1Cc1ccccc1
InChIKey: MSKOUKRULMBARB-UHFFFAOYSA-N
Target: AMP deaminase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q01433
Assay: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 313.38, ALogP 3.51, HBA 2, HBD 1, PSA 49.57, QED 0.92
Compound (SMILES): COc1cc2nc(C)nc(N[C@H](C)c3cc(N)cc(C(F)(F)F)c3)c2cc1C1CCN(C(=O)COCCCC(=O)N[C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](C)c2ccc(-c3scnc3C)cc2)C(C)(C)C)CC1
InChIKey: AIHGVELLLJOFHL-AHHHCUNGSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Binding affinity to GST-tagged human SOS1 (564 to 1049 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as ternary complex formation by measuring dissociation constant incubated for 15 mins in the presence of 6His tagged human VCB by fluorescence polarization-based displacement assay
Measurement: Kd = 17.4 nM (pChEMBL 7.760000228881836)
Descriptors: MW 1030.23
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccccc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: CDRHMFVWJYVLGL-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Leishmania infantum
UniProt: A4HSF7
Assay: Disruption of HIS-FLAG-tagged recombinant Leishmania infantum TryR dimerization expressed in Escherichia coli Rossetta BL21 (DE3) cells incubated for 16 hrs by ELISA analysis
Measurement: IC50 > 75000 nM (pChEMBL 4.125)
Descriptors: MW 546.72, ALogP 3.29, HBA 7, HBD 2, PSA 102.18, QED 0.2
Compound (SMILES): [Se]=P(c1ccccn1)(c1ccccn1)c1ccccn1
InChIKey: GJECUVCYQUIMCB-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as inhibition constant
Measurement: Ki = 53.72 nM (pChEMBL 7.269999980926514)
Descriptors: MW 344.22
Compound (SMILES): CC1(C)CN(C(N)=O)c2ccccc2N1Cc1ccc(OC(F)(F)F)cc1
InChIKey: JTLSJIQQAZDAOU-UHFFFAOYSA-N
Target: AMP deaminase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q01433
Assay: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 379.38, ALogP 4.27, HBA 3, HBD 1, PSA 58.8, QED 0.87
Compound (SMILES): CC(N)C(=O)NC1CSCc2cc3cc(c2)CSC(C(=O)NC(C)C(N)=O)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(Cc2c[nH]cn2)NC(=O)C(C(C)O)NC(=O)C(CSC3)NC(=O)C(CCCNC(=N)N)NC(=O)C(C)NC(=O)C2CCCN2C(=O)C(Cc2c[nH]c3ccccc23)NC(=O)C(CCCNC(=N)N)NC1=O
InChIKey: SJBURJCQSMMNIC-UHFFFAOYSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of human plasmin using H-d-VLK-AM as substrate assessed as inhibition constant by fluorescence plate reader analysis
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1879.19
Compound (SMILES): O=c1cc(CCc2ccc(O)c(O)c2)oc2cccc(O)c12
InChIKey: YXXPWDNDPDOQGZ-UHFFFAOYSA-N
Target: DNA polymerase eta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y253
Assay: Inhibition of C-terminal 6xHis-tagged human DNA polymerase eta (1 to 511 residues) expressed in Escherichia coli BL21 DE3 using 5'-IRD700-GCAGGTCGACTCCAAAG-3' primer/ 5'-TCGGTACCGGGTTAGCCTTTGGAGTCGACCTGC-3' template as DNA substrate incubated for 60 mins in presence of Mg2+ by bromophenol blue staining based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 298.29, ALogP 2.7, HBA 5, HBD 3, PSA 90.9, QED 0.65
Compound (SMILES): O=c1c(OCCO)c(-c2ccc(O)c(O)c2)oc2cc(O)cc(O)c12
InChIKey: YJDSHSSMZYNEPP-UHFFFAOYSA-N
Target: DNA polymerase eta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y253
Assay: Inhibition of C-terminal 6xHis-tagged human DNA polymerase eta (1 to 511 residues) expressed in Escherichia coli BL21 DE3 using 5'-IRD700-GCAGGTCGACTCCAAAG-3' primer/ 5'-TCGGTACCGGGTTAGCCTTTGGAGTCGACCTGC-3' template as DNA substrate incubated for 60 mins in presence of Mg2+ by bromophenol blue staining based assay
Measurement: IC50 = 87500 nM (pChEMBL 4.059999942779541)
Descriptors: MW 346.29, ALogP 1.65, HBA 8, HBD 5, PSA 140.59, QED 0.45
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4ccc(Cl)c(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: NAUMQOWVCNOPGB-INIZCTEOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R mutant (unknown origin)
Measurement: IC50 = 0.053 nM (pChEMBL 10.279999732971191)
Descriptors: MW 547.41, ALogP 5.54, HBA 7, HBD 1, PSA 85.81, QED 0.31
Compound (SMILES): COc1cc(F)cc2c(N3CCN4c5c(F)cccc5OC[C@@H]4C3)c(C#N)nnc12
InChIKey: WXVYORSFYSHIOF-ZDUSSCGKSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Positive allosteric modulation of human mGluR2
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 409.4, ALogP 2.88, HBA 7, HBD 0, PSA 74.51, QED 0.64
Compound (SMILES): NCCCCCCN1CCC(OC(=O)Nc2ccc(F)cc2-c2ccc(F)c(Cl)c2)CC1
InChIKey: ZDFAGRMEOOJZOO-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 465.97, ALogP 5.82, HBA 4, HBD 2, PSA 67.59, QED 0.46
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1)C(N)=O
InChIKey: IOIVYVYLDQJIMW-ONFFMKDPSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant
Measurement: Ki = 161.8 nM (pChEMBL 6.789999961853027)
Descriptors: MW 457.51, ALogP -1.67, HBA 8, HBD 5, PSA 203.27, QED 0.18
Compound (SMILES): CSc1c(C#N)c(=O)c2ccc(F)cc2n1-c1c(Cl)cccc1Cl
InChIKey: AWQZXHDLUBADMM-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of recombinant human Cav1.2
Measurement: IC50 = 24200 nM (pChEMBL 4.619999885559082)
Descriptors: MW 379.24, ALogP 5.03, HBA 4, HBD 0, PSA 45.79, QED 0.59
Compound (SMILES): Cc1ccc(-c2ccnc(Nc3ccc(N4CCN(C)CC4)c(C(F)(F)F)c3)n2)cc1
InChIKey: JGQOMJGZCRMYPO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Binding affinity to Mycobacterium tuberculosis recombinant N-terminal His-tagged PknB (1 to 331 residues) expressed in Escherichia coli DH5alpha cells by microscale thermophoresis analysis
Measurement: Kd = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 427.47, ALogP 4.97, HBA 5, HBD 1, PSA 44.29, QED 0.64
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)CC1
InChIKey: QSUSOTUHCHGTAN-SVBPBHIXSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 613.58, ALogP 3.41, HBA 7, HBD 2, PSA 105.9, QED 0.32
Compound (SMILES): C=CC(=O)Nc1ccc2[nH]c(=O)n(C3CCN(Cc4ccc(-c5[nH]c(=O)c(C)nc5-c5ccccc5)cc4)CC3)c2c1
InChIKey: CGWRGCGZPRWFTG-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of wild-type AKT3 (unknown origin) by HTRF KinEASE assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 560.66, ALogP 5.02, HBA 6, HBD 3, PSA 115.88, QED 0.24
Compound (SMILES): CC(C)n1nc(N2CC(C(C)(C)O)C2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: NSIQQHYATFPGEC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR T790M/del (746 to 750 residues) mutant autophosphorylation in human PC-9/ER1 cells harboring harboring EGFR T790M/del (746 to 750 residues) mutant preincubated for 60 mins followed by EGF stimulation and measured after 8 mins by SULFO-TAG based electrochemiluminescent assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 537.65, ALogP 2.96, HBA 12, HBD 2, PSA 143.95, QED 0.34
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](N)CC(N)=O)C(=O)N1)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC1=O
InChIKey: RNLOEYVMCLFNOF-DKWPCZOMSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production incubated for 30 mins by LANCE cAMP assay
Measurement: EC50 = 9446 nM (pChEMBL 5.03000020980835)
Descriptors: MW 1093.36
Compound (SMILES): O=c1c(Cl)c(COc2cccc(Cl)c2C2CC2)[nH]c2nc(-c3ccccc3)nn12
InChIKey: HGXDDSUVIVWHNN-UHFFFAOYSA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: Displacement of BODIPY 500/510 C4 from human FABP3 expressed in Escherichia coli incubated for 30 mins by FP assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 427.29, ALogP 4.85, HBA 5, HBD 1, PSA 72.28, QED 0.49
Compound (SMILES): COc1ccc(S(=O)(=O)Nc2ccccc2C#Cc2ccc(C(=O)O)nc2)c2ncccc12
InChIKey: GKBULVNTEXLKJY-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of human MCT4 in human SNU-398 cells assessed as inhibition of radioactive lactate efflux preincubated for 30 mins followed by D(+)glucose and measured after 4 hrs by dialysis based UHPLC-ESI-Q-Orbitrap-MS analysis
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 459.48, ALogP 3.54, HBA 6, HBD 2, PSA 118.48, QED 0.44
Compound (SMILES): COc1ccc(CN(C)CCCCCCCCCCCCn2cc(C=O)c3cc(OC)ccc32)cc1
InChIKey: PVQHHKRPWIYTFO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 492.7, ALogP 7.5, HBA 5, HBD 0, PSA 43.7, QED 0.14
Compound (SMILES): O=C1CC2Cc3ccsc3C2=NN1CCCCN1CCN(Cc2ccccc2)CC1
InChIKey: NYFCTSGIAUTTNF-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 HEK cell membrane incubated for 60 mins by microplate beta scintillation counting analysis
Measurement: Ki = 3969 nM (pChEMBL 5.400000095367432)
Descriptors: MW 422.6, ALogP 3.45, HBA 5, HBD 0, PSA 39.15, QED 0.64
Compound (SMILES): C=CCn1c(=O)c2cnc(Nc3ccc4c(c3)CNCC4(C)C)nc2n1-c1cccc(C(C)(C)O)n1
InChIKey: WOBLPQMIMKNCIR-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 485.59, ALogP 3.52, HBA 9, HBD 3, PSA 109.89, QED 0.36
Compound (SMILES): CCC(C)COc1ccc(C(C)(C)C)cc1NC(=O)c1nnn(-c2cc(OC)ccc2OC)c1C
InChIKey: IPTTUGLAFBGALO-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 480.61, ALogP 5.57, HBA 7, HBD 1, PSA 87.5, QED 0.43
Compound (SMILES): COC1CCN(c2nccc(Nc3cc4c(cn3)c(C(N)=O)cn4C(C)C)n2)CC1
InChIKey: GBQZWJZYHRNIFT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR L858R mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 peptide as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 363 nM (pChEMBL 6.440000057220459)
Descriptors: MW 409.49, ALogP 2.86, HBA 8, HBD 2, PSA 111.19, QED 0.64
Compound (SMILES): COc1ccc(S(=O)(=O)Nc2ccc3c(c2)CCCN3C(=O)c2ccco2)cc1
InChIKey: UWBPPRSRIFBYGK-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 5620 nM (pChEMBL 5.25)
Descriptors: MW 412.47, ALogP 3.68, HBA 5, HBD 1, PSA 88.85, QED 0.69
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccccc2Cl)CCC1(O)c1cccc(O)c1
InChIKey: VZKYGOFDBBGOOF-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 277.1 nM (pChEMBL 6.559999942779541)
Descriptors: MW 402.92, ALogP 2.89, HBA 4, HBD 2, PSA 64.01, QED 0.81
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(C[C@H](C)C(N)=O)c2C#N)cc1
InChIKey: KIWBVAQAICXQKZ-KRWDZBQOSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 cells assessed as reduction in ADP production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 250 uM ATP by ADP-Glo luminescent assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 436.52, ALogP 4.9, HBA 5, HBD 1, PSA 101.89, QED 0.44
Compound (SMILES): C=CC(=O)Nc1ccccc1C1CCNc2c(C(N)=O)c(-c3cc(OC)c(C)c(OC)c3)nn21
InChIKey: ZEIZIRVZVXALHM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 461.52, ALogP 3.5, HBA 7, HBD 3, PSA 120.5, QED 0.46
Compound (SMILES): O=C(Nc1cnccc1-c1cccc(F)c1F)c1ccnc(NC(=O)C2CC2)c1
InChIKey: NUQDMQZYZIYAFS-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GST tagged GSK-3beta (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 394.38, ALogP 4.02, HBA 4, HBD 2, PSA 83.98, QED 0.68
Compound (SMILES): Clc1cc(Cl)cc(Nc2nc(-c3nc(-c4ccccc4Cl)cs3)cs2)c1
InChIKey: OULVZVSWNBPRDB-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 5302 nM (pChEMBL 5.28000020980835)
Descriptors: MW 438.79, ALogP 7.64, HBA 5, HBD 1, PSA 37.81, QED 0.36
Compound (SMILES): O=C(Cc1ccc(C(F)(F)F)cc1)N1CCN(c2ccc(O)cc2)CC1
InChIKey: NESIORPNFVEQNP-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P48163
Assay: Inhibition of His-tagged human recombinant full length ME1 using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 364.37, ALogP 3.3, HBA 3, HBD 1, PSA 43.78, QED 0.91
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: CSIMBPGKVWPGTE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Binding affinity to Mycobacterium tuberculosis recombinant N-terminal His-tagged PknB (1 to 331 residues) expressed in Escherichia coli DH5alpha cells by microscale thermophoresis analysis
Measurement: Kd = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 447.89, ALogP 5.31, HBA 5, HBD 1, PSA 44.29, QED 0.59
Compound (SMILES): c1ccc(COC2CCN(Cc3cn4ccccc4n3)CC2)nc1
InChIKey: VUGZNXOHTNGPHN-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 2290 nM (pChEMBL 5.639999866485596)
Descriptors: MW 322.41, ALogP 2.91, HBA 5, HBD 0, PSA 42.66, QED 0.72
Compound (SMILES): c1cc(CNCCCNC2CCCCC2)ccc1CNCCCNC1CCCCC1
InChIKey: HAKFGEFAVSVPJO-UHFFFAOYSA-N
Target: Stromal cell-derived factor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48061
Assay: Inhibition of SDF-1 alpha induced cell migration in human SUP-T1 cells pre-incubated for 30 mins followed by SDF-1 alpha addition measured after 3 hrs by cell Titer-96 reagent based analysis
Measurement: IC50 = 621.4 nM (pChEMBL 6.210000038146973)
Descriptors: MW 414.68, ALogP 4.49, HBA 4, HBD 4, PSA 48.12, QED 0.34
Compound (SMILES): CN(C)c1cccc2c(S(=O)(=O)N[C@H](C(=O)Nc3ccc(C(=O)NO)cc3)c3ccccc3)cccc12
InChIKey: QXIIXGYKPYLMDY-VWLOTQADSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 using fluorogenic as substrate measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 24.4 nM (pChEMBL 7.610000133514404)
Descriptors: MW 518.6, ALogP 3.68, HBA 6, HBD 4, PSA 127.84, QED 0.21
Compound (SMILES): CCOC(=O)N1C[C@@H]2C[C@H]1CN2c1nc(-c2cnc(N)c(OC(F)F)n2)cc(C2CC2)n1
InChIKey: KBBJVNCJPHHXME-RYUDHWBXSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 447.45, ALogP 2.41, HBA 9, HBD 1, PSA 119.59, QED 0.71
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@H](Cc2ccccc2)NC(=O)C2CCN(C(=O)OCc3ccccc3)CC2)CC1
InChIKey: FCORXOBTLFNQOU-SZAHLOSFSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 639.8, ALogP 3.83, HBA 8, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): O=C(CCCCCCNCc1ccc([N+](=O)[O-])cc1)NO
InChIKey: BNOSPXWJXXMXQF-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant HDAC3 expressed in baculovirus by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 295.34, ALogP 2.14, HBA 5, HBD 3, PSA 104.5, QED 0.27
Compound (SMILES): NC(=O)c1ccccc1-c1ccc(N2CCC[C@@H](NC(=O)Nc3ccc(C(F)(F)F)cc3)C2=O)cc1
InChIKey: PURUWPLYNJDKEY-JOCHJYFZSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: cAMP Assay: FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays. A mixture of forskolin (5 μM final for FPR2 or 10 μM final for FPR1) and IBMX (200 μM final) were added to 384-well Proxiplates (Perkin-Elmer) pre-dotted with test compounds in DMSO (1% final) at final concentrations in the range of 0.020 nM to 100 μM. Chinese Hamster Ovary cells (CHO) overexpressing human FPR1 or human FPR2 receptors were cultured in F-12 (Ham's) medium supplemented with 10% qualified FBS, 250 μg/ml zeocin and 300 μg/ml hygromycin (Life Technologies). Reactions were initiated by adding 2,000 human FPR2 cells per well or 4,000 human FPR1 cells per well in Dulbecco's PBS (with calcium and magnesium) (Life Technologies) supplemented with 0.1% BSA (Perkin-Elmer). The reaction mixtures were incubated for 30 min at room temperature. The level of intracellular cAMP was determined using the HTRF HiRange cAMP assay reagent kit (Cisbio) according to manufacturer's instruction. Solutions of cryptate conjugated anti-cAMP and d2 flurorophore-labelled cAMP were made in a supplied lysis buffer separately. Upon completion of the reaction, the cells were lysed with equal volume of the d2-cAMP solution and anti-cAMP solution. After a 1-h room temperature incubation, time-resolved fluorescence intensity was measured using the Envision (Perkin-Elmer) at 400 nm excitation and dual emission at 590 nm and 665 nm.
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 496.49, ALogP 4.79, HBA 3, HBD 3, PSA 104.53, QED 0.47
Compound (SMILES): O=C1CCc2cc(OCCN3CCCC3c3cccc(F)c3)ccc2N1
InChIKey: ZHGIASFMHGIOQA-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of full length human ALDH1A1 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis
Measurement: IC50 >= 100000 nM (pChEMBL 4)
Descriptors: MW 354.43, ALogP 3.93, HBA 3, HBD 1, PSA 41.57, QED 0.88
Compound (SMILES): Cc1ncsc1-c1ccc2c(c1)OCCOCCOC[C@@H](NC(=O)C[C@H]1N=C(c3ccc(Cl)cc3)c3c(sc(C)c3C)-n3c(C)nnc31)COCCOCCOCC(=O)N[C@@H](C(C)(C)C)C(=O)N1C[C@H](O)C[C@H]1C(=O)NC2
InChIKey: GMEHQGWGMMKWAX-NGMXXZSUSA-N
Target: von Hippel-Lindau disease tumor suppressor (SINGLE PROTEIN), Homo sapiens
UniProt: P40337
Assay: Binding affinity to VHL (unknown origin) assessed as dissociation constant by isothermal titration calorimetry assay
Measurement: Kd = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 1118.78
Compound (SMILES): Cc1cccc2c(C(=O)N3CCN(Cc4ccc(C(=O)NO)cc4)CC3)c[nH]c12
InChIKey: LOYLSJNIQXFWSL-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using fluorogenic peptide RHKKAc-AMC as substrate by fluorescence-based assay
Measurement: IC50 = 2250 nM (pChEMBL 5.650000095367432)
Descriptors: MW 392.46, ALogP 2.55, HBA 4, HBD 3, PSA 88.67, QED 0.47
Compound (SMILES): CCC(=O)Nc1cc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)ccc1C
InChIKey: YKDZIFFKQUNVHH-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of AKT1 phosphorylation in human HCT-116 cells
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 375.44, ALogP 3.58, HBA 7, HBD 3, PSA 107.14, QED 0.61
Compound (SMILES): COc1cc2c(cc1OC)C(=O)/C(=C/c1ccc([N+](=O)[O-])cc1)C2
InChIKey: NRZJZJKDBFVBRU-NTUHNPAUSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of self-induced amyloid beta (1 to 42) (unknown origin) disaggregation by ThT-based fluorometric assay
Measurement: IC50 = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 325.32, ALogP 3.43, HBA 5, HBD 0, PSA 78.67, QED 0.49
Compound (SMILES): N#Cc1nc2c(nc1C#N)-c1ccc(O)cc1C2=O
InChIKey: WWMOLNPIOMEHFL-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P40818
Assay: Inhibition of human USP8 using Ub-AMC as substrate
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 248.2, ALogP 1.14, HBA 6, HBD 1, PSA 110.66, QED 0.64
Compound (SMILES): COc1cc(N2CC[C@@H](Oc3ccc(N4C[C@H](F)[C@@H](C)[C@@H]4CC(=O)O)cc3)[C@H](C)C2)c(Cl)cn1
InChIKey: CYIZNYHHAGFMBN-YLZPZURSSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q76JU9
Assay: Positive allosteric modulation of mouse GPR40
Measurement: EC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 491.99, ALogP 4.67, HBA 6, HBD 1, PSA 75.13, QED 0.6
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCCCCN(C)Cc1ccc(O)cc1
InChIKey: UUXMKUDVTHMKFM-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 60610 nM (pChEMBL 4.21999979019165)
Descriptors: MW 478.68, ALogP 7.2, HBA 5, HBD 1, PSA 54.7, QED 0.16
Compound (SMILES): Cc1onc(-c2ccccc2)c1C=CCCCCCNC(=O)CS
InChIKey: IUTMTBXLLAOWGT-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant HDAC3/NCOR2 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 344.48, ALogP 4.27, HBA 4, HBD 2, PSA 55.13, QED 0.53
Compound (SMILES): CC(C)(C(=O)Nc1ccc(-c2cncc(C(F)(F)F)n2)cn1)c1csc(NS(=O)(=O)C2CC2)n1
InChIKey: CZIDGRDZSFIUHX-UHFFFAOYSA-N
Target: CTP synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17812
Assay: Inhibition of human CTPS1 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 512.54, ALogP 3.83, HBA 8, HBD 2, PSA 126.83, QED 0.49
Compound (SMILES): COc1ccc(S(=O)(=O)N2CCN(c3cccnc3)CC2C(=O)NO)cc1
InChIKey: LHPNKVRYCBRQPZ-UHFFFAOYSA-N
Target: Matrilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P09237
Assay: Inhibition of recombinant human MMP7 using Mca-Pro-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 20 to 30 mins by fluorescence microplate reader analysis
Measurement: IC50 = 27680 nM (pChEMBL 4.559999942779541)
Descriptors: MW 392.44, ALogP 0.48, HBA 7, HBD 2, PSA 112.07, QED 0.56
Compound (SMILES): O=C(NC1CC1)c1nc2cccnn2c1-c1cc(F)c(Cl)c(F)c1
InChIKey: GYZISZRYVGZYRR-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: The PDE4A3, PDE4B1, PDE4C1 and PDE4D3 assays: The PDE4A3, PDE4B1, PDE4C1 and PDE4D3 assays use the Scintillation Proximity Assay (SPA) technology to measure the inhibition of human recombinant PDE4A1, PDE4B3, PDE4C1, and PDE4D3 enzyme activity by compounds in vitro. The PDE4A1, PDE4B3, PDE4C1, and PDE4D3 assays are run in parallel using identical parameters, except for the concentration of enzyme (80 pM PDE4A3, 40 pM PDE4B3, 40 pM PDE4C1 and 10 pM PDE4D). The assays are performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE4A3, PDE4B1, PDE4C1, and PDE4D to convert ¿20% of substrate (1 μM cAMP consisting of 20 nM 3H-cAMP+980 uM cold cAMP) and a range of inhibitors. Reactions are incubated for 30 min at 25° C. The addition of 20 uL of 8 mg/ml yitrium silicate SPA beads (Perkin Elmer) stops the reaction. The plates are sealed (TopSeal, Perkin Elmer) and the beads are allowed to settle for 8 hrs, after which they are read on the Trilux Microbeta overnight.
Measurement: IC50 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 348.74, ALogP 3.22, HBA 4, HBD 1, PSA 59.29, QED 0.74
Compound (SMILES): O=C(NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO)c1cccc(C(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1
InChIKey: LJOOWNHZCTUDSG-XRSDMRJBSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of human recombinant MMP-2 expressed in mouse cells using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated with enzyme for 3 hrs followed by substrate addition and measured every 10 secs for 15 mins by fluorescence based analysis
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 1232.62
Compound (SMILES): O=[N+]([O-])C1=Cc2cc(C#Cc3ccc(CO)cc3)ccc2OC1C(F)(F)F
InChIKey: DMAGHFXHRJCHRS-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Binding affinity to dopamine 5 receptor (unknown origin)
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 375.3, ALogP 3.52, HBA 4, HBD 1, PSA 72.6, QED 0.5
Compound (SMILES): COc1ccc(C(c2c(-c3ccccc3)n(O)c3ccccc23)N2CCN(C)CC2)cc1
InChIKey: BBAJRFXAJHAPJE-UHFFFAOYSA-N
Target: Bcl-2-like protein 11/Bcl-2-related protein A1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16548
Assay: Inhibition of Bfl-1/Bim (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 427.55, ALogP 4.89, HBA 5, HBD 1, PSA 40.87, QED 0.46
Compound (SMILES): O=C(Cn1c(=O)[nH]c2ccccc21)N1CCN(c2ncc(Cl)cc2-c2cnc(N3CCC(O)CC3)nc2)CC1
InChIKey: RZSJEXJNWYEMBF-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 549.04, ALogP 2.14, HBA 9, HBD 2, PSA 123.48, QED 0.39
Compound (SMILES): COc1cccc(C2(O)CCN(C(=O)CCc3cccc(C(F)(F)F)c3)CC2CN(C)C)c1
InChIKey: GALQJRZZGDWBSC-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 464.53, ALogP 3.94, HBA 4, HBD 1, PSA 53.01, QED 0.67
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@H](Cc2ccccc2)NC(=O)c2ccncc2)CC1
InChIKey: JEJVZDGRLIYMOS-RRPNLBNLSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 499.62, ALogP 2.49, HBA 7, HBD 2, PSA 101.72, QED 0.42
Compound (SMILES): Cc1cc(Oc2ccc(S(=O)(=O)N(Cc3ccccc3)c3ccc(C(=O)O)c(O)c3)cc2)cc(C)c1Cl
InChIKey: MHWCKPSUVMUWFL-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 1672 nM (pChEMBL 5.78000020980835)
Descriptors: MW 538.02, ALogP 6.55, HBA 5, HBD 2, PSA 104.14, QED 0.26
Compound (SMILES): O=C(/C=C/c1ccc(S(=O)(=O)Nc2cc(F)cc(F)c2)cc1)NO
InChIKey: DAXZERYOFDXUJS-ZZXKWVIFSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 354.33, ALogP 2.28, HBA 4, HBD 3, PSA 95.5, QED 0.44
Compound (SMILES): CC1(C)c2ccccc2N(Cc2ccc(C(=O)NO)cc2)C1c1cccnc1
InChIKey: HGCZGYHCBRKJNB-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using FLUOR DE LYS fluorometric substrate pre-incubated for 15 mins and followed by substrate addition and measured after 60 mins by microplate reader assay
Measurement: IC50 = 2170 nM (pChEMBL 5.659999847412109)
Descriptors: MW 373.46, ALogP 4.24, HBA 4, HBD 2, PSA 65.46, QED 0.53
Compound (SMILES): Cc1cc(C)n(CC(=O)N2CCN(c3ccccc3-c3ccccc3)CC2)n1
InChIKey: PDMXTXOJHWGUDX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 374.49, ALogP 3.52, HBA 4, HBD 0, PSA 41.37, QED 0.7
Compound (SMILES): CC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@]1(C)CCCCCC/C=C\CCC[C@@](C)(C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC1=O)[C@@H](C)O
InChIKey: SOTXVDFJHYKWOG-NJUAEABQSA-N
Target: Protein Mdm4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15151
Assay: Binding affinity to human MDM4 assessed as dissociation constant by ITC assay
Measurement: Kd = 43.3 nM (pChEMBL 7.360000133514404)
Descriptors: MW 2085.39
Compound (SMILES): N#Cc1cn(Cc2ccccc2)c2c(NCCCc3ccccc3)ncnc12
InChIKey: SXEQBLZMVHHAJH-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP (unknown origin)
Measurement: IC50 = 20414 nM (pChEMBL 4.690000057220459)
Descriptors: MW 367.46, ALogP 4.4, HBA 5, HBD 1, PSA 66.53, QED 0.49
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccnc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: UWDRPHXOMMPVSE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Binding affinity to Mycobacterium tuberculosis recombinant N-terminal His-tagged PknB (1 to 331 residues) expressed in Escherichia coli DH5alpha cells by microscale thermophoresis analysis
Measurement: Kd = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 448.88, ALogP 4.71, HBA 6, HBD 1, PSA 57.18, QED 0.58
Compound (SMILES): NC1CCN(c2c(-c3cc(F)cc(F)c3)cnc3ccc(-c4cccc(O)c4)cc23)CC1
InChIKey: ZTBPVQXPLLMZGW-UHFFFAOYSA-N
Target: Somatostatin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30872
Assay: Agonist activity at human SST1 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 431.49, ALogP 5.48, HBA 4, HBD 2, PSA 62.38, QED 0.45
Compound (SMILES): CC[C@](C)(O)C#Cc1cc2c(ccn2-c2ccnc(N)n2)cn1
InChIKey: ISYRCGISNANONJ-KRWDZBQOSA-N
Target: Tau-tubulin kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6IQ55
Assay: Inhibition of TTBK2 (unknown origin)
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 307.36, ALogP 1.91, HBA 6, HBD 2, PSA 89.85, QED 0.71
Compound (SMILES): Cc1ccc(S(=O)(=O)O)cc1.Cc1ccsc1C(=O)Nc1cc(CN2CCN(C(=O)CO)CC2)ccc1/C=C/c1n[nH]c2ccccc12
InChIKey: SIJKXSMUXNJNQM-HRNDJLQDSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human Aurora B kinase expressed in SUM149 cells
Measurement: IC50 = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 515.64, ALogP 3.99, HBA 6, HBD 3, PSA 101.56, QED 0.35