lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NC1CCN(c2c(-c3cc(F)cc(F)c3)cnc3ccc(-c4ccccc4O)cc23)CC1
InChIKey: ISEVDBBZOFRQNF-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: cAMP Assay : Four days prior to the assay, 5,000 Chinese hamster ovary cells (CHO-K1, ATCC #CCL-61) stably expressing the human SSTR2 are plated in each well of a 96-well tissue culture-treated plate in Ham's F12 growth media (ThermoFisher #10-080-CM) supplemented with 10% donor bovine serum (Gemini Bio-Products #100-506), 100 U/mL penicillin; 100 ug/mL streptomycin; 2 mM L-glutamine (Gemini Bio-Products #400-110) and 0.2 mg/mL hygromycin B (GoldBio #31282-04-9). The cells are cultured at 37° C., 5% CO2 and 95% humidity. On the day of the assay, the media is aspirated and the cells are treated with 50 μL of 1.6 μM NKH477 (Sigma #N3290) plus various dilutions of compounds of the invention in assay buffer [1× Hank's Balanced Salt Solution (ThermoFisher #SH3058802), 0.5 mM HEPES pH 7.4, 0.1% bovine serum albumin, 0.2 mM 3-Isobutyl-1-methylxanthine (IBMX, VWR #200002-790)]. The cells are incubated for 20 minutes at 37° C. (the final concentration of the compounds of the invention are typically 0-10,000 nM). The cells are treated with 50 μL of lysis buffer (HRTF cAMP kit, Cisbio). The lysate is transferred to 384-well plates and cAMP detection and visualization antibodies are added and incubated for 1-24 hours at room temperature. The time-resolved fluorescent signal is read with a Tecan M1000Pro multiplate reader. The intracellular cAMP concentrations are calculated by regression to a standard curve and are plotted vs. the concentration of the compounds of the invention and the EC50 of the compounds are calculated using standard methods. All data manipulations are in GraphPad Prism v6.
Measurement: EC50 < 10 nM (pChEMBL 8)
Descriptors: MW 431.49, ALogP 5.48, HBA 4, HBD 2, PSA 62.38, QED 0.45
Compound (SMILES): COc1ccc(OC)c(-n2nnc(C(=O)Nc3cc(B4OC(C)(C)C(C)(C)O4)cc(C(C)(C)C)c3)c2C)c1
InChIKey: LGEMQQVBCMNEFB-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 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 520.44
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCC3(CC2)CC(=O)c2cc(OCCO)ccc2O3)c([N+](=O)[O-])c1
InChIKey: LUGSQNZOCSCMMA-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 477.5, ALogP 1.62, HBA 9, HBD 2, PSA 162.3, QED 0.46
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(C)c3c2)[C@@H](C)n2nnnc2N1C
InChIKey: QUNODOWDVLTAHL-SNVBAGLBSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by HTRF analysis
Measurement: IC50 = 5220 nM (pChEMBL 5.28000020980835)
Descriptors: MW 338.38, ALogP 1.78, HBA 7, HBD 2, PSA 104.62, QED 0.74
Compound (SMILES): N#Cc1c(N)ncnc1N1CSC[C@H]1c1nc2cccc(Cl)c2c(=O)n1-c1cccs1
InChIKey: ZGWOQMKRSVYPJK-AWEZNQCLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) incubated for 90 mins by [gamma-33P]-ATP based scintillation counting method
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 467.97, ALogP 3.6, HBA 10, HBD 1, PSA 113.72, QED 0.49
Compound (SMILES): Cc1nc2c(c(-c3cc(C(N)=O)c(O)c4c3OCCO4)cn2CC(=O)Nc2cc(N3CCN(C)C[C@@H]3C)nc(F)c2Cl)c(=O)n1C
InChIKey: CJMWXCIZQLNCEA-AWEZNQCLSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 655.09, ALogP 2.25, HBA 12, HBD 3, PSA 170.07, QED 0.26
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3c(C#N)cnn3C)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: WAWDCCVZPCGIJC-OALUTQOASA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 542.58, ALogP 2.71, HBA 10, HBD 3, PSA 155.21, QED 0.32
Compound (SMILES): Nc1ccc(S(=O)(=O)Nc2ccsc2-c2nc(-c3ccccc3)no2)cc1
InChIKey: BKPTXQBGBXVYFW-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA IX
Measurement: Ki = 10780 nM (pChEMBL 4.96999979019165)
Descriptors: MW 398.47, ALogP 3.85, HBA 7, HBD 2, PSA 111.11, QED 0.49
Compound (SMILES): CN(C)C[C@@H]1CN(C(=O)Cc2cc(F)c(F)cc2F)CC[C@@]1(O)c1cccc(O)c1
InChIKey: JMDFENKDWRFUQU-OPAMFIHVSA-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 = 126.9 nM (pChEMBL 6.900000095367432)
Descriptors: MW 422.45, ALogP 2.65, HBA 4, HBD 2, PSA 64.01, QED 0.73
Compound (SMILES): CCNC(=O)c1ccnc(CNCC(=O)N(CC)CCN(C)C)c1
InChIKey: WXFDDWMINUVYFL-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of KDM5B (unknown origin ) by Alphascreen assay
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 335.45, ALogP 0.33, HBA 5, HBD 2, PSA 77.57, QED 0.64
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc3cnn(C)c3cc2N2CC[C@@H](N)C2)n1
InChIKey: JWBXEWFBXJNXBU-OAHLLOKOSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 461.5, ALogP 2.97, HBA 8, HBD 2, PSA 111.19, QED 0.47
Compound (SMILES): Cc1cc(C)cc(-c2cncc(-c3ccc4c(O)cccc4c3)c2C(=O)NCCN)c1
InChIKey: DLQDTOXPYMCBJT-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 411.51, ALogP 4.58, HBA 4, HBD 3, PSA 88.24, QED 0.45
Compound (SMILES): C[C@H]1COCCN1c1cc(NC(=O)Cn2cc(-c3cc(Cl)c(O)c(C(N)=O)c3)c3c(=O)n(C)cnc32)c(Cl)cn1
InChIKey: NDRFFOKFYGUOKD-ZDUSSCGKSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 10 nM (pChEMBL 8)
Descriptors: MW 586.44, ALogP 2.77, HBA 10, HBD 3, PSA 157.6, QED 0.31
Compound (SMILES): NC1CCN(c2c(-c3cc(F)cc(F)c3)cnc3ccc(-c4cccc(F)c4O)cc23)CC1
InChIKey: VOLGHANNFIVAPZ-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 449.48, ALogP 5.62, HBA 4, HBD 2, PSA 62.38, QED 0.43
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCC3(CC2)CC(=O)c2ccc(Br)cc2O3)c([N+](=O)[O-])c1
InChIKey: LZYIJZSCAFQEKR-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant
Measurement: Ki = 61.2 nM (pChEMBL 7.210000038146973)
Descriptors: MW 496.34, ALogP 3.01, HBA 7, HBD 1, PSA 132.84, QED 0.51
Compound (SMILES): Cc1onc(-c2ccccc2)c1C=CCCCCCNC(=O)C(C)S
InChIKey: IIDXNZPWTMVERQ-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 358.51, ALogP 4.66, HBA 4, HBD 2, PSA 55.13, QED 0.51
Compound (SMILES): CCCCOc1ccc(C(C)(C)C)cc1NC(=O)c1nnn(-c2ccccc2OC)c1C
InChIKey: BFEGOGQVNYZSMN-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 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 436.56, ALogP 5.31, HBA 6, HBD 1, PSA 78.27, QED 0.48
Compound (SMILES): CC(C)(C)C1CCC(c2cc(C(=O)N3CCC(Oc4cc(N5CCNCC5)ccc4C#N)CC3)ccc2O[C@H]2CCNC2)CC1.Cl.Cl
InChIKey: BJLUZOOHVQRTRQ-BZWZXOHXSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of full length beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)/N-terminal biotinylated human BCL9 HD2 (350 to 375 residues) protein-protein interaction incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 613.85, ALogP 5.71, HBA 7, HBD 2, PSA 89.86, QED 0.41
Compound (SMILES): O=C(CCCCCCNC(=O)C(O)(O)C(F)(F)F)Nc1ncc(-c2ccc(Br)cc2)s1
InChIKey: XFFMCHUCKPYGQZ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) incubated for 3 hrs by chemiluminescent assay
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 524.36, ALogP 3.82, HBA 6, HBD 4, PSA 111.55, QED 0.28
Compound (SMILES): COc1cc(N2CCC(N(C)C)CC2)ccc1Nc1ncc(C(=O)OC(C)C)c(-c2cn(C)c3ccccc23)n1
InChIKey: TZVJCWOLQMYNMO-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S mutant (unknown origin) using TK-substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 10 mins by HTRF assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 542.68, ALogP 5.48, HBA 9, HBD 1, PSA 84.75, QED 0.29
Compound (SMILES): COc1cc(Nc2nc(-c3nc(-c4ccccc4F)cs3)cs2)cc(OC)c1
InChIKey: XHVXCBIACIZRRP-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 413.5, ALogP 5.83, HBA 7, HBD 1, PSA 56.27, QED 0.43
Compound (SMILES): Nc1cc(Oc2ccc3c(C(=O)Nc4ccc(F)c(C(F)(F)F)c4)cccc3c2)ncn1
InChIKey: HJFDTNBKNJFDQP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Mus musculus
UniProt: P35918
Assay: Inhibition of mouse recombinant GST-fused VEGFR2 kinase domain expressed in baculovirus expression system using poly-Glu-Tyr (4:1) as substrate measured after 10 mins in presence of gamma-[33P]-ATP by scintillation counting analysis
Measurement: IC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 442.37, ALogP 5.41, HBA 5, HBD 2, PSA 90.13, QED 0.41
Compound (SMILES): CC(=O)O[C@@]12CO[C@@H]1C[C@H](O)[C@@]1(C)C(=O)[C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](OCCC(=O)NCCCC[C@H](NC(=O)CC[C@@H](NC(=O)[C@H](C)NC(=O)/C=C/c4ccc(F)cc4Cl)C(N)=O)C(=O)O)[C@@H](NC(=O)OC(C)(C)C)c4ccccc4)C[C@@](O)([C@@H](OC(=O)c4ccccc4)[C@H]21)C3(C)C
InChIKey: BQJQHHXUJDRCSN-HBSVTOSBSA-N
Target: Nucleotide-binding oligomerization domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC29
Assay: Antagonist activity at NOD2 in human HEK-Blue hNOD2 cells assessed as inhibition of MDP-induced NOD2 activation
Measurement: IC50 = 13120 nM (pChEMBL 4.880000114440918)
Descriptors: MW 1389.92
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(=O)O
InChIKey: UCYMPMGFNQYIPQ-HXUWFJFHSA-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 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 460.9, ALogP 5.9, HBA 5, HBD 2, PSA 98.9, QED 0.37
Compound (SMILES): O=S(=O)(Nc1cc(Sc2ccccc2)c(O)c2ccccc12)c1c(F)c(F)c(F)c(F)c1F
InChIKey: ZXJHEANDHXHGMV-UHFFFAOYSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of STAT3 phosphorylation in human MOLM-13 cells
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 497.47, ALogP 6.19, HBA 4, HBD 2, PSA 66.4, QED 0.15
Compound (SMILES): CC(C)(O)c1ccc(-c2cn3cc(Cl)cc3c(=O)[nH]2)cc1
InChIKey: OAXRVCSFISVGCI-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 302.76, ALogP 3.18, HBA 3, HBD 2, PSA 57.5, QED 0.76
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(CC)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: BAPLSMNZBLGGHQ-NXZAIFCTSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from kappa opioid receptor (unknown origin) assessed as inhibition constant incubated for 180 mins by competitive radioligand binding assay
Measurement: Ki = 1170 nM (pChEMBL 5.929999828338623)
Descriptors: MW 380.49, ALogP 2.7, HBA 5, HBD 0, PSA 42.01, QED 0.58
Compound (SMILES): CC[C@](C)(O)C#Cc1cc2c(ccn2-c2cc(OC)nc(N)n2)cn1
InChIKey: HPJVZSVEIGCFJP-SFHVURJKSA-N
Target: Tau-tubulin kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6IQ55
Assay: Inhibition of TTBK2 (unknown origin)
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 337.38, ALogP 1.92, HBA 7, HBD 2, PSA 99.08, QED 0.71
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc(C#N)c4)n3)cc2C(F)(F)F)CC1
InChIKey: BGJRDIYMVFGUSL-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 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 438.46, ALogP 4.53, HBA 6, HBD 1, PSA 68.08, QED 0.65
Compound (SMILES): CC1(C)CNCc2cc(Nc3ncc4c(=O)n(-c5c(Cl)cccc5Cl)ccc4n3)ccc21
InChIKey: ALMVORCDEJHPLC-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 = 283 nM (pChEMBL 6.550000190734863)
Descriptors: MW 466.37, ALogP 5.21, HBA 6, HBD 2, PSA 71.84, QED 0.43
Compound (SMILES): CCOC(=O)c1ncc2[nH]c3ccc(OC)cc3c2c1COC
InChIKey: BYMDBFGHCDTBMT-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P34903
Assay: Binding affinity to human recombinant GABAA alpha3 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 314.34, ALogP 3.05, HBA 5, HBD 1, PSA 73.44, QED 0.73
Compound (SMILES): O=C(Nc1cnccc1-c1ccccc1Cl)c1ccnc(NC(=O)C2CC2)c1
InChIKey: FIUNUJMCHFAOKT-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 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 392.85, ALogP 4.4, HBA 4, HBD 2, PSA 83.98, QED 0.67
Compound (SMILES): Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(N4CCN(CCNC(=O)CCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)nc3)cc3c2cnn3C(C)C)c(=O)[nH]1
InChIKey: LRMNSTSNSCJHGZ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 (unknown origin)
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 914.04, ALogP 3.07, HBA 14, HBD 5, PSA 233.06, QED 0.07
Compound (SMILES): O=C(Nc1cccc(-n2cc(CNc3ccc(N4CC(O)C4)c(C(=O)N4CCCCC4)c3)nn2)c1)c1cc(F)cc(F)c1
InChIKey: YVNLBZDKGHSKPK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 587.63, ALogP 4.22, HBA 8, HBD 3, PSA 115.62, QED 0.28
Compound (SMILES): Cc1cccc(-n2c(=O)c3cnc(Nc4ccc(N5CCN(C)CC5)cc4)nc3n2-c2cccc(C(C)(C)O)n2)c1
InChIKey: JAWYXFZJQSZEGT-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 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 550.67, ALogP 4, HBA 10, HBD 2, PSA 104.34, QED 0.33
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CS)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)O
InChIKey: IFMJSYQQPWJQEL-AHNRHFCJSA-N
Target: Proprotein convertase subtilisin/kexin type 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NBP7
Assay: Inhibition of PCSK9 mediated LDLR degradation in human HepG2 cells assessed as restoration of LDLR
Measurement: EC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 3370.87
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ccccc1
InChIKey: BDARZHMPJRWQLB-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 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 470.98, ALogP 5.05, HBA 4, HBD 1, PSA 75.71, QED 0.57
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2O[C@@H](C)C/C=C\[C@H]3c2ccccc2)cc1
InChIKey: QASNVFRJXGIQNZ-JKZIFQNUSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 542.64, ALogP 7.35, HBA 5, HBD 3, PSA 104.82, QED 0.2
Compound (SMILES): C[C@@H]1[C@@H]2Cc3ccccc3[C@]1(C)CCN2CCN1CCCC1
InChIKey: OEILHFLXSQZBDT-LSTHTHJFSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma 2 receptor (unknown origin) assessed as inhibition constant in presence of (+)-SKF10047 by radioligand binding assay
Measurement: Ki = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 298.47, ALogP 3.31, HBA 2, HBD 0, PSA 6.48, QED 0.84
Compound (SMILES): Cc1cc2c(=O)[nH]c(-c3ccc(C(C)(C)O)cc3)cn2c1
InChIKey: HIVDAZHBOHYAOK-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 282.34, ALogP 2.83, HBA 3, HBD 2, PSA 57.5, QED 0.76
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCCCN5CCC(O)CC5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: WBHILSPRBDBBDX-ZNOUKXQUSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from recombinant human histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition constant incubated for 30 mins by liquid scintillation analysis
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 466.71, ALogP 5.23, HBA 4, HBD 1, PSA 35.94, QED 0.58
Compound (SMILES): O=C(CCCCCn1cc(-c2ccc3ncnc(Nc4ccc(Br)cc4F)c3c2)nn1)NO
InChIKey: NIGXIHUCIANGDC-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 514.36, ALogP 4.6, HBA 8, HBD 3, PSA 117.85, QED 0.17
Compound (SMILES): C#CCO[C@@H]1[C@H](C)[C@@H](COS(=O)(=O)C=C)O[C@H]1n1nc(-c2ccc(C)cc2)c2c(N)ncnc21
InChIKey: IWODHENDABKBRB-OYSWKTHDSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Inhibition of LYN (unknown origin) at 1 uM by kinase-profiling analysis
Measurement: IC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 483.55, ALogP 2.43, HBA 10, HBD 1, PSA 131.45, QED 0.38
Compound (SMILES): CCOC(=O)c1[nH]c2ccc(F)cc2c1CN1CCN(c2ccccc2)CC1
InChIKey: FARUCCZQJHBFSU-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-spiperone from human D4 receptor expressed in CHO cells assessed as inhibition constant
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 381.45, ALogP 3.81, HBA 4, HBD 1, PSA 48.57, QED 0.68
Compound (SMILES): O=C(Nc1cnccc1-c1ccc(Cl)cc1Cl)c1ccnc(NC(=O)C2CC2)c1
InChIKey: SSTMOSQZONYWBG-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 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 427.29, ALogP 5.05, HBA 4, HBD 2, PSA 83.98, QED 0.6
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccccc4)c3c2)C(C)(C)n2nnnc2N1C
InChIKey: KHSAHYKLUPESPP-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by HTRF analysis
Measurement: IC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 414.47, ALogP 3.31, HBA 7, HBD 2, PSA 104.62, QED 0.53
Compound (SMILES): CCCCn1c2cc(OCc3ccc(F)cc3)ccc2c2cc[n+](Cc3ccccc3)c(C)c21.[Br-]
InChIKey: JGWBVGJOVYUQAZ-UHFFFAOYSA-M
Target: Serine/threonine-protein kinase PLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H4B4
Assay: Inhibition of PLK3 (unknown origin)
Measurement: IC50 = 1810 nM (pChEMBL 5.739999771118164)
Descriptors: MW 453.58, ALogP 6.96, HBA 2, HBD 0, PSA 18.04, QED 0.23
Compound (SMILES): Cc1cc2c(cc1C1(c3ccc(C(=O)O)cc3)OCCO1)C(C)(C)CCC2(C)C
InChIKey: IDVFJUSYLBAGDL-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P48443
Assay: Agonist activity at RXRgamma (unknown origin)
Measurement: EC50 = 232 nM (pChEMBL 6.630000114440918)
Descriptors: MW 394.51, ALogP 5.29, HBA 3, HBD 1, PSA 55.76, QED 0.77
Compound (SMILES): c1cn(Cc2ccc(Nc3nc(-c4nccs4)cs3)cc2)cn1
InChIKey: FCMDCMRHZDEBSC-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 = 48.55 nM (pChEMBL 7.309999942779541)
Descriptors: MW 339.45, ALogP 4.26, HBA 7, HBD 1, PSA 55.63, QED 0.59
Compound (SMILES): Cc1onc(-c2ccccc2)c1COCCCCCNC(=O)[C@@H](C)S
InChIKey: SXOJHTOVXGQVDN-OAHLLOKOSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 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 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 362.5, ALogP 3.77, HBA 5, HBD 2, PSA 64.36, QED 0.5
Compound (SMILES): C#CCOc1ccccc1-c1csc(-c2csc(Nc3cccc(F)c3)n2)n1
InChIKey: ACQHWRINVFGEAM-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 = 1039 nM (pChEMBL 5.980000019073486)
Descriptors: MW 407.5, ALogP 5.83, HBA 6, HBD 1, PSA 47.04, QED 0.41
Compound (SMILES): Cc1cn(-c2cccc(F)c2)c2ccc(C(=O)NS(C)(=O)=O)cc12
InChIKey: DNBLZRUMMGYSLS-UHFFFAOYSA-N
Target: Sodium channel protein type 1 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.1/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 346.38, ALogP 2.77, HBA 4, HBD 1, PSA 68.17, QED 0.79
Compound (SMILES): CCc1ccc(-c2cc(-c3ccc(S(=O)(=O)N[C@H](C(=O)O)C(C)C)cc3)no2)s1
InChIKey: YUKZMFUVSSRXAN-IBGZPJMESA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of MMP12 (unknown origin)
Measurement: IC50 = 0.566 nM (pChEMBL 9.25)
Descriptors: MW 434.54, ALogP 4.02, HBA 6, HBD 2, PSA 109.5, QED 0.55
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(N(S(=O)(=O)c3cccs3)S(=O)(=O)c3cccs3)ccc21
InChIKey: PSYTUNZMUBFHEK-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 = 2860 nM (pChEMBL 5.539999961853027)
Descriptors: MW 534.66, ALogP 4.58, HBA 8, HBD 0, PSA 104.97, QED 0.36
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCN(C)Cc1ccc(O)cc1
InChIKey: FMUARSILENPDKK-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 = 2060 nM (pChEMBL 5.690000057220459)
Descriptors: MW 422.57, ALogP 5.64, HBA 5, HBD 1, PSA 54.7, QED 0.29
Compound (SMILES): N=C(N)NCCP(=O)(O)CP(=O)(O)O
InChIKey: MNWZTJZEYHDOIP-UHFFFAOYSA-N
Target: Isopentenyl-diphosphate Delta-isomerase (SINGLE PROTEIN), Escherichia coli (strain K12)
UniProt: Q46822
Assay: Competitive inhibition of Escherichia coli IPP isomerase assessed as inhibition constant by Lineweaver-burk plot analysis
Measurement: Ki = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 245.11, ALogP -1.12, HBA 3, HBD 6, PSA 156.73, QED 0.2
Compound (SMILES): COc1ccc(OC)c(-n2nnc(C(=O)Nc3ccccc3C(C)(C)C)c2C)c1
InChIKey: VTTAHBDGCKLNOT-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 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 394.48, ALogP 4.14, HBA 6, HBD 1, PSA 78.27, QED 0.7
Compound (SMILES): N#C[C@@H]1C[C@H](F)CN1C(=O)[C@@H](N)Cc1cc(Cl)c(Cl)cc1Cl
InChIKey: WQDMIHXZLGRFFI-RVBZMBCESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG by thallium flux assay
Measurement: IC50 = 97700 nM (pChEMBL 4.010000228881836)
Descriptors: MW 364.64, ALogP 2.98, HBA 3, HBD 1, PSA 70.12, QED 0.84
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CC[C@@H]1CC[C@@H](CNC(=O)c2cc3ccccc3[nH]2)C1
InChIKey: QIUNPJREZURMGC-UVPKRVSESA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylscopolamine from human dopamine D2 receptor expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 25400 nM (pChEMBL 4.590000152587891)
Descriptors: MW 461.61, ALogP 4.14, HBA 5, HBD 3, PSA 96.27, QED 0.49
Compound (SMILES): CC(=O)N1c2ccc(NC(=O)CCc3cccc(Cl)c3)cc2C2(CCCCC2)C1(C)C
InChIKey: SDXOTRLCWRFJCY-UHFFFAOYSA-N
Target: Thyrotropin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P16473
Assay: Antagonist activity at human TSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 439, ALogP 6.26, HBA 2, HBD 1, PSA 49.41, QED 0.61
Compound (SMILES): Clc1cc(Cl)cc(Nc2nc(-c3nccs3)cs2)c1
InChIKey: BEVMNCUXVXPGPP-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 = 55.7 nM (pChEMBL 7.25)
Descriptors: MW 328.25, ALogP 5.32, HBA 5, HBD 1, PSA 37.81, QED 0.71
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)CC1
InChIKey: QSUSOTUHCHGTAN-SXOMAYOGSA-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): O=C(NNCCC1CCCC1)c1ccc(Br)cc1
InChIKey: ZLEUBTRYAAACNU-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
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 = 1080 nM (pChEMBL 5.96999979019165)
Descriptors: MW 311.22, ALogP 3.26, HBA 2, HBD 2, PSA 41.13, QED 0.65
Compound (SMILES): CC(C)n1nc(N)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: OHTAVMVCBUOHHE-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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 439.51, ALogP 2.33, HBA 11, HBD 2, PSA 146.5, QED 0.46
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccc(F)cc4)n3)cc2C(F)(F)F)CC1
InChIKey: PAHHDKVUHLNVHT-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 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 431.44, ALogP 4.8, HBA 5, HBD 1, PSA 44.29, QED 0.6
Compound (SMILES): CCCCCCCCN1C(=O)c2ccc(C(=O)OCc3cn(-c4ccc(S(N)(=O)=O)cc4)nn3)cc2C1=O
InChIKey: XQOBEXOEPZAQRJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human transmembrane carbonic anhydrase 9 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 50.04 nM (pChEMBL 7.300000190734863)
Descriptors: MW 539.61, ALogP 3.23, HBA 9, HBD 1, PSA 154.55, QED 0.21
Compound (SMILES): O=C(Cn1c(CCCN2CCN(c3cccc(Cl)c3Cl)CC2)nc2cc(Br)c(Br)cc21)NCc1ccccc1
InChIKey: AKQWVRLMOLBNQU-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human D2 receptor expressed in HEK293T cells assessed as beta-arrestin recruitment preincubated for 10 mins with coelenterazine followed by compound addition and measured after 10 mins by BRET assay
Measurement: EC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 694.3, ALogP 6.94, HBA 5, HBD 1, PSA 53.4, QED 0.21
Compound (SMILES): Cc1cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc2n([C@@H]2CCC[C@@]2(C)O)c1=O
InChIKey: APLCQEOLIQVWQN-OXQOHEQNSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 31.4 nM (pChEMBL 7.5)
Descriptors: MW 435.55, ALogP 1.41, HBA 8, HBD 2, PSA 117.42, QED 0.75
Compound (SMILES): CC1CN(c2nc3ccc(Cl)cc3s2)CCC1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: VEWDWCKHTFNUTA-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPAR-alpha ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 479.43, ALogP 6.16, HBA 5, HBD 1, PSA 62.66, QED 0.44
Compound (SMILES): COc1cccc(S(=O)(=O)n2ccc3cnc(Nc4ccc(N5C[C@@H](C)N[C@@H](C)C5)cc4)nc32)c1
InChIKey: GLRBJDQXLPBXND-HDICACEKSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) using TK as substrate incubated for 1 hr in presence of biotin/ATP by HTRF assay
Measurement: IC50 = 29.6 nM (pChEMBL 7.53000020980835)
Descriptors: MW 492.61, ALogP 3.61, HBA 9, HBD 2, PSA 101.38, QED 0.42
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(Cl)c3F)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: RWBHBQMJZIBEBQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 432.89, ALogP 5.73, HBA 4, HBD 3, PSA 82.28, QED 0.33
Compound (SMILES): COc1ccc(/C=c2\c(=O)[nH]n3c(=O)c4ccccc4nc23)cc1
InChIKey: QNBMVIAVMRUVAY-UVTDQMKNSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX-2 using acetylcholinesterase as substrate preincubated for 10 mins followed by substrate addition and measured after 30 sec by Ellman's method
Measurement: IC50 = 488.2 nM (pChEMBL 6.309999942779541)
Descriptors: MW 319.32, ALogP 1.09, HBA 5, HBD 1, PSA 76.46, QED 0.6
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCc5ccccn5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: NJQGZXLJDWIJDQ-MASCHLQQSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from Sprague-Dawley rat brain membrane histamine H3 receptor assessed as inhibition constant incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 416.61, ALogP 5.98, HBA 3, HBD 0, PSA 25.36, QED 0.61
Compound (SMILES): O=C(OCCCN1CCN(c2ccncc2)CC1)c1cc2ccccc2o1
InChIKey: LHUNAHOZEVLINA-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Binding affinity to human D3 receptor expressed in CHO cells assessed as inhibition constant by scintillation counting method
Measurement: Ki > 10 nM (pChEMBL 8)
Descriptors: MW 365.43, ALogP 3.2, HBA 6, HBD 0, PSA 58.81, QED 0.49
Compound (SMILES): COCCn1cc(-c2n[nH]c3cnc(N4C5CCC4C(=O)N(C)C5)nc23)cn1
InChIKey: AVXYKYUDFKFQSI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: Phosphorylated (P): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including phosphorylated (P)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 382.43, ALogP 0.67, HBA 8, HBD 1, PSA 105.06, QED 0.69
Compound (SMILES): COc1ccc(S(=O)(=O)N(c2c(C)cc(-c3cccc(C(F)(F)F)c3)cc2C(=O)NO)N(C)C)cc1
InChIKey: IPKOKUIXGDZGRK-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of TACE (unknown origin)
Measurement: IC50 = 633 nM (pChEMBL 6.199999809265137)
Descriptors: MW 523.53, ALogP 4.48, HBA 6, HBD 2, PSA 99.18, QED 0.35
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCCN(C)Cc1ccc(O)cc1
InChIKey: VSDNNQHHKUMUKF-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 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 450.62, ALogP 6.42, HBA 5, HBD 1, PSA 54.7, QED 0.21
Compound (SMILES): NC[C@@H](NC(=O)c1ccc(-c2ccncc2)cc1)c1ccccc1
InChIKey: MLGGUGPIWDHBAI-LJQANCHMSA-N
Target: cGMP-dependent protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13237
Assay: Inhibition of PRKG2 (unknown origin)
Measurement: IC50 = 2.512 nM (pChEMBL 8.600000381469727)
Descriptors: MW 317.39, ALogP 3.18, HBA 3, HBD 2, PSA 68.01, QED 0.76
Compound (SMILES): O=C(CCCCCCNCc1ccc2ccccc2c1)NO
InChIKey: ZTHTYSUCXALYGC-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli BL21 (DE3) cells by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 300.4, ALogP 3.39, HBA 3, HBD 3, PSA 61.36, QED 0.38
Compound (SMILES): Cc1ccc2c(c1)C(=O)CC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)O2
InChIKey: WUECJPFZZOZFNC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 3550.5 nM (pChEMBL 5.449999809265137)
Descriptors: MW 431.47, ALogP 2.56, HBA 7, HBD 1, PSA 132.84, QED 0.58
Compound (SMILES): N#C/C(=C/c1cccc(-c2ncnc3[nH]ccc23)c1)C(N)=O
InChIKey: PBACTZXZNFJQGT-GHXNOFRVSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) incubated for 45 mins by LC-MS/MS analysis
Measurement: IC50 = 0.77 nM (pChEMBL 9.109999656677246)
Descriptors: MW 289.3, ALogP 2.02, HBA 4, HBD 2, PSA 108.45, QED 0.57
Compound (SMILES): C[C@H]1CN(c2nc3ccc(Cl)cc3s2)CCN1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: KPLTXOWOJNWKCJ-AWEZNQCLSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 480.42, ALogP 4.82, HBA 6, HBD 1, PSA 65.9, QED 0.52
Compound (SMILES): CC(C)N1C[C@H](C)[C@H](NC(=O)c2cc3ccc(Br)cc3[nH]2)C1
InChIKey: LOSOPIVYJSAUGK-MEDUHNTESA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Agonist activity at D4R (unknown origin) by camp reporter assay
Measurement: EC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 364.29, ALogP 3.39, HBA 2, HBD 2, PSA 48.13, QED 0.88
Compound (SMILES): Nc1ccc(/N=N/c2ccc(/C=C/c3ccc(/N=N/c4ccc(N)c5ccccc45)cc3S(=O)(=O)O)c(S(=O)(=O)O)c2)c2ccccc12
InChIKey: BEOHKTZPLVXCFG-NKPXSSHVSA-N
Target: Sentrin-specific protease 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BQF6
Assay: Binding Assay: The binding of SPI-01 to the enzyme-substrate complex was investigated. CSP analysis was carried out on the 40 kDa complex of 15N-labeled full length precursor SUMO-1-GGHSTV (SUMO-1-FL) with unlabeled SENP1-C603S. An equimolar amount of SPI-01 was added to the 1:1 enzyme-substrate complex. The only observed CSP on the 15N-labeled precursor SUMO-1-FL was on the C-terminal residues S99 and V101 (FIGS. 7 and 8) (Song et al., PNAS 101:14373-8 (2004)). This result indicates that SPI-01 binds the enzyme-substrate complex at the interface between SENP and the C-terminal tails of precursor SUMO-FL. X-ray crystal structures showed that the C-terminal tail of precursor SUMO sits in and projects out of the catalytic tunnel of SENPs (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006)). In the case of SENP1, the region that interacts with the projected C-terminus is predominantly acidic and favors the C-terminus of SUMO-1, which is polar and positively charged, over that of SUMO-2, whose C-terminus is mainly hydrophobic (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006); and Shen et al., The Biochemical Journal 397:279-88 (2006)).
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 678.75, ALogP 8.65, HBA 10, HBD 4, PSA 210.22, QED 0.05
Compound (SMILES): COc1ccc(-c2nc(N3CCOCC3)c3sc(CN(C)c4ccc(C(=O)NO)cc4)cc3n2)cn1
InChIKey: ZPDSADGKXLOVPB-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human HDAC1 by fluorogenic assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 506.59, ALogP 3.35, HBA 10, HBD 2, PSA 112.94, QED 0.29
Compound (SMILES): Cc1cnc(NC(=O)N[C@@H]2CCCN(c3ccc(-c4ccccc4NS(C)(=O)=O)cc3F)C2=O)cn1
InChIKey: LPEZWOPFRXAYNB-HXUWFJFHSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
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. A calibration curve was constructed with an external cAMP standard at concentrations ranging from 1 μM to 0.1 pM by plotting the fluorescent intensity ratio from 665 nm emission to the intensity from the 590 nm emission against cAMP concentrations. The potency and activity of a compound to inhibit cAMP production was then determined by fitting to a 4-parametric logistic equation from a plot of cAMP level versus compound concentrations.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 512.57, ALogP 3.28, HBA 6, HBD 3, PSA 133.39, QED 0.46
Compound (SMILES): Cc1c(C(=O)N[C@@H](CCC2CC2)C(=O)Nc2ccc(C#N)cc2)[nH]c2c1C(=O)CC(C)(C)C2
InChIKey: OWORSODZTADOQX-IBGZPJMESA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Inhibition of DNMT1 (unknown origin)
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 446.55, ALogP 4.28, HBA 4, HBD 3, PSA 114.85, QED 0.59