lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)c1ccc(OCCN2CCN(Cc3ccccc3)CC2)cc1O
InChIKey: ALCYGBKZIXJPOZ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B using kynuramine as substrate measured after 30 mins by fluorimetric assay
Measurement: IC50 = 10200 nM (pChEMBL 4.989999771118164)
Descriptors: MW 354.45, ALogP 2.79, HBA 5, HBD 1, PSA 53.01, QED 0.78
Compound (SMILES): Cc1cc(C(c2cccc(Cl)c2)c2cccc(Cl)c2)sc1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: IYEVEBSAVHGBPY-IBGZPJMESA-N
Target: C3a anaphylatoxin chemotactic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16581
Assay: Agonist activity at C3a receptor in human MDM cells assessed as induction of intracellular calcium release measured at 1 sec interval for => 200 secs by Fluo-3 AM dye-based FLIPR assay
Measurement: EC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 533.48, ALogP 4.99, HBA 4, HBD 5, PSA 128.3, QED 0.14
Compound (SMILES): O=[N+]([O-])c1ccc2c(c1)=[N+]([O-])C1(CCCC1)[N+]=2[O-]
InChIKey: LCFCUDVZEQEHDG-UHFFFAOYSA-N
Target: Separin (SINGLE PROTEIN), Homo sapiens
UniProt: Q14674
Assay: Inhibition of epitope-tagged separase (unknown origin) using Rad21-MCA as substrate preincubated for 1 hr followed by substrate addition measured after 3 hrs by fluorescence assay
Measurement: IC50 = 17100 nM (pChEMBL 4.769999980926514)
Descriptors: MW 249.23, ALogP -0.14, HBA 4, HBD 0, PSA 95.28, QED 0.3
Compound (SMILES): CC/C=C\C(=O)Nc1cc(Nc2nc(C)cc(-c3cn(C)c4ccc(F)cc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: AFZIZZRKADLGAJ-KTKRTIGZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild-type EGFR (unknown origin) using substrate-biotin by ELISA-based mobility shift assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 559.69, ALogP 5.74, HBA 8, HBD 2, PSA 87.55, QED 0.23
Compound (SMILES): Nc1nc(-c2cccc(CO)c2)nc2sc(-c3ccccc3)nc12
InChIKey: JSVSRNHXYPGLRB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cells assessed as inhibition of NECA-induced increase in cAMP accumulation preincubated for 10 mins followed by NECA addition by GloSensor cAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 334.4, ALogP 3.49, HBA 6, HBD 2, PSA 84.92, QED 0.6
Compound (SMILES): Cc1nc(NC(=O)OC(C)(C)C)sc1-c1csc(NCCO)n1
InChIKey: WWUPCEYMTCIFHX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Inhibition of recombinant human full length His6-tagged PI4KIII beta expressed in Sf9 cells incubated for 10 mins by scintillation counting method
Measurement: IC50 = 1360 nM (pChEMBL 5.869999885559082)
Descriptors: MW 356.47, ALogP 3.33, HBA 8, HBD 3, PSA 96.37, QED 0.76
Compound (SMILES): CSc1nnc(CCO)n1-c1ccc(Cl)cc1Cl
InChIKey: HDVGCISUSAZPKT-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Inhibition of human TLR8 expressed in HEK-Blue cells assessed as inhibition of R848-induced NF-kappaB activation measured after 24 hrs by quanti-blue based SEAP reporter gene assay
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 304.2, ALogP 2.83, HBA 5, HBD 1, PSA 50.94, QED 0.88
Compound (SMILES): C[C@H](Nc1nccc(N2C(=O)OC[C@@H]2[C@H](C)F)n1)c1ncn2c1COc1cc(C3CC3)ccc1-2
InChIKey: WOOAASQLIKZGJI-SUNYJGFJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay
Measurement: IC50 = 33.4 nM (pChEMBL 7.480000019073486)
Descriptors: MW 464.5, ALogP 4.29, HBA 8, HBD 1, PSA 94.4, QED 0.58
Compound (SMILES): O=C1C=C(n2cc(CCCCl)nn2)C(=O)c2c(O)cccc21
InChIKey: WIOLWYIJJQBFMS-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human P2X7R expressed in HEK293 cells assessed as inhibition of ATP-induced ethidium iodide uptake preincubated for 5 mins followed by ATP induction and measured after 25 mins by fluorescence assay
Measurement: IC50 = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 317.73, ALogP 2.08, HBA 6, HBD 1, PSA 85.08, QED 0.87
Compound (SMILES): O=C(c1c(O)cc(Cl)cc1Cl)N1CC2(CCCC2)C1
InChIKey: IFJWJGKTFFMLBO-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of TNAS binding to human sepiapterin reductase by 19F-NMR spectra analysis
Measurement: IC50 = 4780 nM (pChEMBL 5.320000171661377)
Descriptors: MW 300.19, ALogP 3.72, HBA 2, HBD 1, PSA 40.54, QED 0.86
Compound (SMILES): CCOc1nc(CC)c(CNC(=O)[C@@H](CS)CC(C)C)n1Cc1ccc(-c2ccccc2C(=O)O)c(F)c1
InChIKey: BXOTUFWBXZIMMA-HXUWFJFHSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Displacement of Europium-labeled angiotensin-2 from human AT1 receptor expressed in CHOK1 cell membranes after 120 mins by DELFIA
Measurement: Ki = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 541.69, ALogP 5.61, HBA 6, HBD 3, PSA 93.45, QED 0.24
Compound (SMILES): O=C(NCc1cccc(C(F)(F)F)c1)c1cccc2c1cnn2-c1ccccc1F
InChIKey: XKIIHVGDWUWKJX-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Antagonist activity at recombinant CCR1 (unknown origin) expressed in non-adherent cells co-expressing Galpha16 assessed as inhibition of MIP-1 alpha-induced calcium flux by Fluo-4 NW or Calcium 4 dye based FLIPR TETRA assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 413.37, ALogP 5.11, HBA 3, HBD 1, PSA 46.92, QED 0.47
Compound (SMILES): O=C(c1c2c(nn1-c1ccc(F)cc1)CCC(NCc1ccc(F)cc1)C2)N1CCCCC1
InChIKey: SMVFIZSERNBAJQ-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor (unknown origin) expressed in HEK293 cell membranes after 120 mins by microbeta scintillation counting method
Measurement: Ki = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 450.53, ALogP 4.42, HBA 4, HBD 1, PSA 50.16, QED 0.63
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)cc(=O)n(Cc2cc(Br)ccc2C(=O)OC)c1=O
InChIKey: BODIBWMUDWNFME-QGZVFWFLSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of recombinant human DPP4 expressed in baculovirus infected Sf9 insect cells using Gly-Pro-AMC as substrate measured at 60 secs interval for 20 mins by fluorescence assay
Measurement: IC50 = 395 nM (pChEMBL 6.400000095367432)
Descriptors: MW 489.37, ALogP 1.56, HBA 8, HBD 1, PSA 99.56, QED 0.51
Compound (SMILES): Cc1ccc(S(=O)(=O)N[C@@H](CC(=O)NC(C)(C)C)C(=O)NCCNC(=O)c2ccccc2)cc1
InChIKey: SCUFZIUNKCLTOL-FQEVSTJZSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of human beta5 20S constitutive proteasome using suc-LLVY-AMC as substrate
Measurement: IC50 = 1410 nM (pChEMBL 5.849999904632568)
Descriptors: MW 488.61, ALogP 1.49, HBA 5, HBD 4, PSA 133.47, QED 0.38
Compound (SMILES): CCCCC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(-c3ccc(-c4cnc([C@@H]5CCCN5C(=O)[C@H](NC(=O)CCCC)c5ccccc5)s4)cc3)cc2)s1)c1ccccc1
InChIKey: PIQFNFGQZBFWLU-YWDQWAANSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 1b infected in human HuH7 replicon cells assessed as reduction in subgenomic viral RNA replication treated for 2 days followed by compound washout and subsequent compound dosing measured after 1 day by SEAP reporter gene assay
Measurement: EC50 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 893.19, ALogP 11.02, HBA 8, HBD 2, PSA 124.6, QED 0.09
Compound (SMILES): Cc1cc(C#N)ccc1O[C@@H](C)COc1cccc(-c2ccnn2C)c1
InChIKey: IPMAECGFJWTQDT-INIZCTEOSA-N
Target: Protein-S-isoprenylcysteine O-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: O60725
Assay: Inhibition of recombinant human ICMT expressed in baculovirus infected Sf9 insect cells using SAM as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by MTase-Glo assay
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 347.42, ALogP 4.11, HBA 5, HBD 0, PSA 60.07, QED 0.67
Compound (SMILES): COc1cc(NC(=O)Nc2nnc(SCc3cc(=O)n4ccc(C)cc4n3)s2)cc(OC)c1
InChIKey: SXMIBJYDUSTCDO-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human full length TRKB expressed in CHO cells assessed as decrease in NGF-induced Ca2+ flux by Calcium 4 dye-based FLIPR TETRA assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 484.56, ALogP 3.81, HBA 10, HBD 2, PSA 119.74, QED 0.3
Compound (SMILES): C=CC(=O)N1CCC(Oc2c(N)ncnc2-c2cc(F)cc(NC(=O)c3ccc(C4CC4)cc3F)c2C)CC1
InChIKey: SQPBHMYMFCISEC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Biochemical Enzyme Assay: The inhibitory activity of the present compounds against Btk was assessed in a biochemical enzyme assay. Assay plates in 384 well format were prepared with 8-point serial dilutions for the test compounds on a Thermo CatX workstation equipped with a Innovadyne Nanodrop Express. The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO. The kinase reactions were started by stepwise addition of 4.5 ul per well of peptide/ATP-solution (4 uM FITC-Ahx-TSELKKWALYDYMPMNAND-NH2, 164 uM ATP) in kinase buffer (50 mM HEPES, pH 7.5, 1 mM DTT, 0.02% Tween20, 0.02% BSA, 0.6% DMSO, 10 mM beta-glycerophosphate, and 10 uM sodium orthovanadate, 18 mM MgCl2, 1 mM MnCl2) and 4.5 ul per well of enzyme solution (6.4 nM full-length human recombinant BTK) in kinase buffer. Kinase reactions were incubated at 30° C. for 60 minutes and subsequently terminated by addition of 16 ul per well of stop solution (100 mM HEPES pH 7.5, 5% DMSO, 0.1% Caliper coating reagent, 10 mM EDTA, and 0.015% Brij35). Kinase reactions were analyzed on a Caliper LC3000 workstation by separating phosphorylated and unphosphorylated peptides and kinase activities were calculated from the amounts of newly formed phospho-peptide. Inhibition data were calculated by comparison to control reactions without enzyme (100% inhibition) and without inhibitors (0% inhibition). The concentration of inhibitor required for 50% inhibition (IC50) was calculated from the inhibition in response to inhibitor concentrations.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 533.58, ALogP 5, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): CNCCN1CCCC1
InChIKey: GYGYDOOXVKDZCF-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Inhibition of full-length Halo-tagged human CARM1 (1 to 608 residues) expressed in 293-F cells using [3H]-SAM and biotinylated histone peptides by scintillation proximity based radiometric assay
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 128.22, ALogP 0.3, HBA 2, HBD 1, PSA 15.27, QED 0.59
Compound (SMILES): Cn1c(Nc2cccc(-c3cncnc3)c2)cc(=O)n(O)c1=O
InChIKey: VUPOVUBXSSFCFO-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of RNase H activity of full length recombinant HIV1 reverse transcriptase assessed as reduction in nonspecific internal cleavage using HTS1 substrate
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 311.3, ALogP 0.98, HBA 8, HBD 2, PSA 102.04, QED 0.7
Compound (SMILES): CC/C=C\C(=O)Nc1cc(Nc2ncc(C#N)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: KSQXFPXLNKIUTF-JYRVWZFOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR T790M/L858R double mutant (unknown origin) using substrate-biotin by ELISA-based mobility shift assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 552.68, ALogP 5.16, HBA 9, HBD 2, PSA 111.34, QED 0.25
Compound (SMILES): Cc1ccccc1OCC(=O)Nc1ccc2c(ccn2C)c1
InChIKey: OEVYBLHOFAXAJL-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of His6-tagged NOTUM purified from human HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 294.35, ALogP 3.5, HBA 3, HBD 1, PSA 43.26, QED 0.8
Compound (SMILES): Cc1cccc(-c2ccnc(N3CCN(C(=O)Nc4ccc(OS(N)(=O)=O)cc4)CC3)n2)c1
InChIKey: XTZCWVQOKQSBGP-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 93300 nM (pChEMBL 4.03000020980835)
Descriptors: MW 468.54, ALogP 2.39, HBA 7, HBD 2, PSA 130.75, QED 0.59
Compound (SMILES): NC[C@H]1O[C@@H](O[C@@H](c2cn(Cc3ccc(COc4ccc(C(=O)c5ccccc5)cc4)cc3)nn2)[C@H]2O[C@@H](n3ccc(=O)[nH]c3=O)[C@H](O)[C@@H]2O)[C@H](O)[C@@H]1O.O=C(O)C(F)(F)F
InChIKey: BHFXPMADGMCRJN-LDFZHVOLSA-N
Target: Phospho-N-acetylmuramoyl-pentapeptide-transferase (SINGLE PROTEIN), Bacillus subtilis (strain 168)
UniProt: Q03521
Assay: Inhibition of MraY in Bacillus subtilis using UDP-MurNAc-[14C]pentapeptide as substrate by radioactivity scanning assay
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 742.74, ALogP -0.23, HBA 16, HBD 6, PSA 246.5, QED 0.09
Compound (SMILES): Cc1cnc(NC(=O)CCCOc2cncc(Cl)c2)s1
InChIKey: XUPYCHMBUNHQEX-UHFFFAOYSA-N
Target: Protein Tat (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)
UniProt: P04608
Assay: Activation of Tat-mediated HIV1 transcription in HEK293- FlpIn-FM cells harboring LTR driven CBR reporter co-expressing CMV driven CBG reporter assessed as LTR-driven gene expression incubated for 48 hr using Chroma-Glo substrate by luciferase dual reporter cellular assay
Measurement: EC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 311.79, ALogP 3.3, HBA 5, HBD 1, PSA 64.11, QED 0.83
Compound (SMILES): CCCOc1ccc(C[C@H](NC(=O)Cc2c(C)n(C(=O)c3ccc(Cl)cc3)c3ccc(OC)cc23)C(=O)NS(=O)(=O)c2ccc(Cl)c([N+](=O)[O-])c2)cc1
InChIKey: VKOFHICRVRSPIX-YTTGMZPUSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of 5-FAM-tagged Bid-BH3 peptide binding to Bcl2 (unknown origin) by fluorescence polarization assay
Measurement: Ki = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 781.67, ALogP 6.43, HBA 10, HBD 2, PSA 175.94, QED 0.1
Compound (SMILES): CCC(=O)NCC1CCN(c2ccc(NC(=O)Nc3cccc(Oc4ccnc5cc(OC)c(OC)cc45)c3)cc2C(F)(F)F)CC1
InChIKey: OLGYUCMAKXEACW-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of His-tagged cKIT (unknown origin) expressed in Sf9 cells using Poly(4:1 Glu, Tyr) peptide as substrate after 1 hr by ADP-glo kinase assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 651.69, ALogP 7.45, HBA 7, HBD 3, PSA 114.05, QED 0.16
Compound (SMILES): Cn1cc(-c2ccc(N3CCC(C4c5c(F)cccc5-c5cncn54)CC3)cc2F)cn1
InChIKey: ODBJBEMGFKUTHU-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition Activity Assay: IDO1: For testing, 24 μL of enzyme (IDO1) was diluted 100 times with 50 mM KPB to 2400 μL. The concentration of the enzyme solution was 2.6 ng/μL. A 96 well reaction plate (AXYGEN, PCR-96-FLT-C) (hereinafter referred to as the reaction plate) was added with the enzyme solution at 24 μL/well. The blank well was added with 24 μL of KPB [Preparation of KPB buffer (50 mM): 6.805 g of KH2PO4 was weighed using an analytical balance, and placed into a 1000 mL beaker, deionized water was added with a measuring cylinder to 900 ml, the pH was adjusted to 6.5 by 1M KOH, then the mixture was introduced into a 1 L measuring cylinder, and water was added to 1 L. It was stored at 4° C.]. Then, 1 μL of a compound or DMSO was added into the corresponding wells in the reaction plate. Preparation of solution A: 200 μL of 500 mM L-sodium ascorbate were added with 1050 μL of KPB, then the mixture was mixed uniformly for 3 seconds at the maximum speed in a turbine mixer. Solution B: 100 μL of 10 mM tryptophan were added with 100 μL of 100,000 unit/mL catalase, 5 μL of 10 mM methylene blue, and 1050 μL of KPB successively, then the mixture was mixed uniformly for 3 seconds at the maximum speed in a turbine mixer. Then, 1200 μL of solution A and 1200 μL of solution B were taken and mixed uniformly for 3 seconds at the maximum speed in a turbine mixer. The mixture was added to the reaction plate at 24 μL/well. The reaction plate was placed in a plate centrifuge and centrifuged for 15 seconds at the maximum speed, so that the reaction liquids converged to the bottom. The reaction mixture was mixed uniformly for 30 seconds on a shaker, and incubated for 1 hour at 37° C. in a constant temperature incubator. In the reaction plate, 30% (W/V) trichloroacetic acid was added at 10 μL/well, then the mixture was incubated for 15 minutes at 65° C. in an incubator. The reaction plate was centrifuged in a centrifuge for 5 minutes at 4700 RPM at room temperature. Then, 40 μL of the supernatant was transferred from the reaction plate to the corresponding 96 well test plate (Corning, #3599) by a multi-channel pipette. Then, 2% (W/V) 4-(dimethylamino)benzaldehyde/glacial acetic acid solution was added at 40 μL/well, and the mixture was mixed uniformly for 1 minute on a shaker at the maximum speed. After incubation for 2 minutes at room temperature, the absorbance at 480 nm was read on a Synergy HT (BIOTEK) reader.
Measurement: IC50 = 7.65 nM (pChEMBL 8.119999885559082)
Descriptors: MW 431.49, ALogP 5.05, HBA 5, HBD 0, PSA 38.88, QED 0.46
Compound (SMILES): O=C(Nc1ccc2cc(C(=O)Nc3nccs3)ccc2c1)c1ccc(Cl)c(Cl)c1
InChIKey: MRITYVDXXFOOAU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Binding affinity to wild-type human full length CDK4/cyclinD1 (M1 to E303 residues) expressed in mammalian expression system measured after 1 hr by kinomescan method
Measurement: Kd = 8020 nM (pChEMBL 5.099999904632568)
Descriptors: MW 442.33, ALogP 6.11, HBA 4, HBD 2, PSA 71.09, QED 0.4
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)CCC(=O)NCCCOCCOCCOCCCNC(=O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: SBYYENLJESTZAO-MUQYVUFSSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 800.3 nM (pChEMBL 6.099999904632568)
Descriptors: MW 3008.66
Compound (SMILES): COc1cc(N(CC(F)(F)F)c2cccc(C(F)(F)F)c2)cnc1C(=O)[C@H]1C[C@@H]1C(=O)O
InChIKey: WXLRAEUAAAIUAP-KBPBESRZSA-N
Target: Leukotriene C4 synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16873
Assay: Inhibition of human N-terminal His6-tagged LTC4S expressed in Pichia pastoris X33 using LTA4 methyl ester and glutathione as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by LC-MS/MS analysis
Measurement: IC50 = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 462.35, ALogP 4.71, HBA 5, HBD 1, PSA 79.73, QED 0.47
Compound (SMILES): O[C@@H]1CCCC[C@H]1[C@H]1c2ccccc2-c2cncn21
InChIKey: GRXLEHXBNCURNH-FVQBIDKESA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human A172 cells after 24 hrs in presence of IFNgamma by NFK green reagent based assay
Measurement: EC50 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 254.33, ALogP 3, HBA 3, HBD 1, PSA 38.05, QED 0.85
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)NCCc2cn(Cc3ccc([N+](=O)[O-])cc3)nn2)C[C@H](N)[C@H]1NC(C)=O
InChIKey: IVORERVVPLPJMZ-RBZQAINGSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus (A/Puerto Rico/8/1934(H1N1))
UniProt: P03468
Assay: Inhibition of Influenza A virus (A/goose/Guangdong/SH7/2013(H5N1)) Neuraminidase N1 preincubated for 10 mins followed by MUNANA substrate addition and measured after 40 mins by fluorescence method
Measurement: IC50 = 4630 nM (pChEMBL 5.329999923706055)
Descriptors: MW 513.6, ALogP 1.63, HBA 9, HBD 3, PSA 167.3, QED 0.28
Compound (SMILES): Nc1nc2c3ccccc3[nH]c(=S)n2n1
InChIKey: KDMAATNMAUOLFS-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Inhibition of rat cortex adenosine A1 receptor using [3H]CCPA measured after 90 mins by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 217.26, ALogP 1.52, HBA 5, HBD 2, PSA 72, QED 0.56
Compound (SMILES): COC1Cc2ccccc2[C@]2(CC[C@@H](NCC3CCCCC3)CC2)O1
InChIKey: QANFZJPWWAIUST-CTTUZFCVSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma 1 receptor in guinea pig brain cortex membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 343.51, ALogP 4.54, HBA 3, HBD 1, PSA 30.49, QED 0.87
Compound (SMILES): COC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](Cc1ccc(OP(=O)(O)O)cc1)NC(C)=O)C(C)C)[C@@H](C)O
InChIKey: ZAZUFAYZXJARJH-HJHDOSNWSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of STAT3 (unknown origin)
Measurement: Ki = 21900 nM (pChEMBL 4.659999847412109)
Descriptors: MW 773.82, ALogP -1.39, HBA 12, HBD 10, PSA 310.83, QED 0.03
Compound (SMILES): C=C1[C@H](O)[C@H]2[C@@H](OC(=O)c3ccccc3)[C@](C)(OC(C)=O)C[C@]2(O)[C@H](OC(C)=O)[C@@H](C)/C=C/C(C)(C)C(=O)[C@H](OC(C)=O)[C@H]1OC(C)=O
InChIKey: XTKYSUFGBHDBME-WWNHBMMRSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp in doxorubicin-resistant human MCF7/ADR cells assessed as reversal of doxorubicin resistance by measuring doxorubicin IC50 incubated for 48 hrs by MTT assay (Rvb = doxorubicin alone = 64.8 +/- 2.1 uM)
Measurement: IC50 = 20600 nM (pChEMBL 4.690000057220459)
Descriptors: MW 672.72, ALogP 2.8, HBA 13, HBD 2, PSA 189.03, QED 0.26
Compound (SMILES): C[S+]([O-])c1ccc(-c2cnc3ccc(NC4CCN(S(C)(=O)=O)CC4)nn23)cc1
InChIKey: PPOBKVGXDVRWRX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells at holding potential of -90 mV by QPatch clamp method
Measurement: IC50 = 25900 nM (pChEMBL 4.590000152587891)
Descriptors: MW 433.56, ALogP 1.97, HBA 7, HBD 1, PSA 102.66, QED 0.62
Compound (SMILES): COc1cc(-c2nnc(-c3cc(OC(F)(F)F)ccc3-n3cncn3)o2)ccc1OCC1CC1
InChIKey: RLFCRRZRBILIJF-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Negative allosteric modulation of rat mGlu7 receptor expressed in HEK cells co-expressing Galpha15 assessed as reduction in calcium mobilization incubated for 142 secs prior to glutamate addition for 120 secs followed by L-AP4 addition and measured after 40 secs by Fluo-4 AM dye based fluorescence assay
Measurement: IC50 = 1310 nM (pChEMBL 5.880000114440918)
Descriptors: MW 473.41, ALogP 4.68, HBA 9, HBD 0, PSA 97.32, QED 0.36
Compound (SMILES): CN1Cc2nccc(-c3cn(C)nc3-c3ccc(F)cc3)c2C1=O
InChIKey: NGDXEOHYWJHBTJ-UHFFFAOYSA-N
Target: Casein kinase I isoform delta (SINGLE PROTEIN), Homo sapiens
UniProt: P48730
Assay: Inhibition of human CK1delta in presence of [gamma33P]-ATP
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 322.34, ALogP 2.87, HBA 4, HBD 0, PSA 51.02, QED 0.73
Compound (SMILES): Clc1ccc(CNCC2CCN(Cc3ccccc3Cl)CC2)cc1
InChIKey: WCVYQXYTLUYPOK-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Displacement of [125I]-CXCL12 from human CXCR4 receptor expressed in HEK293T cell membranes after 2 hrs by scintillation counting analysis
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 363.33, ALogP 5, HBA 2, HBD 1, PSA 15.27, QED 0.78
Compound (SMILES): COc1cccc(Nc2ncnc3sc4c(c23)CCN(S(=O)(=O)c2ccc(F)cc2F)C4)c1
InChIKey: UVKPXVZXQBKDSK-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: Inhibition of human MNK1 using CREBtide substrate by gamma-[32P]-ATP competitive inhibition assay
Measurement: IC50 = 1880 nM (pChEMBL 5.730000019073486)
Descriptors: MW 488.54, ALogP 4.47, HBA 7, HBD 1, PSA 84.42, QED 0.45
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1ccc(NC(=O)[C@H](Cc2cccs2)NC(=O)c2ccccn2)cc1
InChIKey: JRLTWODULRIQQA-FQEVSTJZSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of USP30 (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 486.62, ALogP 3.2, HBA 6, HBD 3, PSA 117.26, QED 0.45
Compound (SMILES): CN1C(=O)S/C(=C\c2cc(OCc3cncc(NCc4ccncc4)c3)c(O)cc2Br)C1=O
InChIKey: BYRMJKKJMBDNRS-WNFQYIGGSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of recombinant His6-SUMO tagged human CGAS expressed in Escherichia coli BL21/pLys cells incubated for 20 mins by Kinase Glo chemiluminescence assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 527.4, ALogP 4.8, HBA 8, HBD 2, PSA 104.65, QED 0.42
Compound (SMILES): N#Cc1ccnc(N2CCC(NC(=O)[C@H]3CN(C#N)CCO3)C2)c1
InChIKey: PYXOJYSQURVYMA-ARLHGKGLSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: USP30 Biochemical IC50 Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 540 nm; λ Emission 590 nm.
Measurement: IC50 = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 326.36, ALogP -0.17, HBA 7, HBD 1, PSA 105.28, QED 0.77
Compound (SMILES): COCCN1CCN(C(CN2CCC(N3CCCCC3)CC2)c2ccc(F)cc2)CC1
InChIKey: DOXYVRGRYDIYMI-UHFFFAOYSA-N
Target: Hepcidin (SINGLE PROTEIN), Homo sapiens
UniProt: P81172
Assay: Inhibition of human hepcidin-stimulated recombinant C-terminal Halo-tagged human FPN internalization in MDCK cells incubated for 15 to 20 mins by Halo-tagged TMR based fluorescence assay
Measurement: IC50 < 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 432.63, ALogP 3.08, HBA 5, HBD 0, PSA 22.19, QED 0.63
Compound (SMILES): Cn1ccc2c(N3CCN(CCCCOc4ccc5c(c4)NC(=O)CC5)CC3)cccc21
InChIKey: JVPFEJREBIUBMB-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human dopamine D2long receptor (unknown origin) expressed in HEK293T cells co-expressing TEV fused-beta-Arrestin2 and GRK2 assessed as increase in beta-arrestin-2 recruitment after overnight incubation by Tango assay
Measurement: EC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 432.57, ALogP 4.04, HBA 5, HBD 1, PSA 49.74, QED 0.57
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(=O)[C@H](CO)NC(C)=O)C(C)C)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CO)C(N)=O)[C@@H](C)O
InChIKey: JAMJYCIFEJUENN-FKEAHFMHSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 9314 nM (pChEMBL 5.03000020980835)
Descriptors: MW 3502.07
Compound (SMILES): O=C(Nc1cnn(-c2ccccc2)c1)c1ccc(NS(=O)(=O)c2ccccc2)cc1
InChIKey: VAEVBQSUBIGLJX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) incubated for 30 mins by enzyme immunoassay
Measurement: IC50 = 25410 nM (pChEMBL 4.590000152587891)
Descriptors: MW 418.48, ALogP 3.93, HBA 5, HBD 2, PSA 93.09, QED 0.5
Compound (SMILES): CC(C)[C@H](NC(=O)c1ccccc1Br)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)CF
InChIKey: HAGNKILLPGZJLE-BJLQDIEVSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Biological Assay: For exemplary compounds of the disclosure, Ki for inhibition of MALT1 was measured (Table E11). A concentration of 100 nM MALT1 was used for the assay.
Measurement: Ki = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 569.48, ALogP 1.48, HBA 5, HBD 5, PSA 157.48, QED 0.15
Compound (SMILES): C[C@H]1NC(=O)c2cc(-c3cccc4c(=O)n(CC(C)(C)N)c(NC(C)(C)C)nc34)[nH]c21
InChIKey: OZWQMYWGAMLKRZ-GFCCVEGCSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of full length recombinant PIM2 (unknown origin) assessed as reduction in BAD phosphorylation at Ser112 residues preincubated for 30 mins followed by biotinylated BAD addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 422.53, ALogP 3.14, HBA 6, HBD 4, PSA 117.83, QED 0.52
Compound (SMILES): CC[C@H](C)[C@H](Nc1ccc(N(CC(=O)O)S(=O)(=O)c2ccc(OC)cc2)c2ccccc12)C(=O)O
InChIKey: HOHLLQVNARJHRA-FYSMJZIKSA-N
Target: Kelch-like ECH-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14145
Assay: Displacement of FITC-LDEETGEFL-NH2 from human KEAP1 Kelch domain (322 to 609 residues) measured after 30 mins by fluorescence polarization assay
Measurement: IC50 = 1490 nM (pChEMBL 5.829999923706055)
Descriptors: MW 500.57, ALogP 4.04, HBA 6, HBD 3, PSA 133.24, QED 0.36
Compound (SMILES): COc1ccc(C2=NN(C3CCCCCC3)C(=O)[C@@H]3CC=CC[C@H]23)cc1C#Cc1cnco1
InChIKey: ZKKVUOTUBHLPJG-BJKOFHAPSA-N
Target: Class 1 phosphodiesterase PDEB1 (SINGLE PROTEIN), Trypanosoma brucei
UniProt: Q8WQX9
Assay: Inhibition of Trypanosoma brucei PDEB1 catalytic domain (565 to 918 residues) expressed in Escherichia coli BL21 incubated for 20 mins using cAMP as substrate by PDELight HTS cAMP phosphodiesterase Kit based luminometry
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 443.55, ALogP 4.93, HBA 5, HBD 0, PSA 67.93, QED 0.38
Compound (SMILES): O=C(Nc1nc2ccc(Cl)cc2s1)c1cn(-c2ccccc2)nc1-c1ccccc1
InChIKey: PUGCWXBHZFBSAI-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-tagged VEGFR2 (805 to 1356 residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) as substrate incubated for 45 mins by kinase-Glo luminescent assay
Measurement: IC50 = 647 nM (pChEMBL 6.190000057220459)
Descriptors: MW 430.92, ALogP 6.05, HBA 5, HBD 1, PSA 59.81, QED 0.38
Compound (SMILES): Cc1c(-c2ccc3c(c2)CCN3c2ncccc2OC(F)F)n(C)c(=O)[nH]c1=O
InChIKey: NGOQMJOVLWWZTQ-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at wild type human D1R expressed in HEK293 cells assessed as effect on cAMP accumulation incubated for 10 mins by Gs-cAMP Glosensor assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 400.38, ALogP 2.74, HBA 6, HBD 1, PSA 80.22, QED 0.73
Compound (SMILES): Cc1ccc(CN2C(=O)N(c3ccc(Cl)cc3)C(=O)C2CCC(=O)Nc2ccc(C(=O)NO)cc2)cc1
InChIKey: RSMGBZPONOKBDP-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of HDAC11 (unknown origin) using Ac-LeuGlyLys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 520.97, ALogP 4.52, HBA 5, HBD 3, PSA 119.05, QED 0.23
Compound (SMILES): CCc1sc2ncnc(O[C@H](C)C(=O)O)c2c1-c1ccc2ccccc2c1
InChIKey: LECUPUVLYQKJMC-GFCCVEGCSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of N-terminal fluorescein labelled Puma-BH3 peptide from TEV-fused His-tagged human Mcl-1 expressed in Escherichia coliBL21(DE3) pLysS cells after 2 hrs by fluorescence polarization assay
Measurement: Ki = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 378.45, ALogP 4.93, HBA 5, HBD 1, PSA 72.31, QED 0.53
Compound (SMILES): CCCCCCCCCCc1ccc(NC(=O)C(=O)N2C[C@H](Oc3ccc(CCS(=O)(=O)OCC)cc3)[C@H](Oc3ccc(/C=C/S(=O)(=O)OCC)cc3)C2)cc1
InChIKey: CRUPUHJUVOOKRI-IWTNZTPGSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) using pNPP as substrate after 30 mins
Measurement: IC50 = 1080 nM (pChEMBL 5.96999979019165)
Descriptors: MW 813.05, ALogP 7.29, HBA 10, HBD 1, PSA 154.61, QED 0.06
Compound (SMILES): CCOC1C[C@H]2C(C)(C)CCC[C@]2(C(=O)OC)c2c1cc(C(C)C)c(O)c2O
InChIKey: HYOYOOYYLOFIDU-KMXYETGPSA-N
Target: Farnesyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: P14324
Assay: Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged FPPS expressed in Escherichia coli BL21 (DE3) using GPP and IPP as substrate preincubated for 30 mins followed by substrate addition by continuous spectrophotometric assay
Measurement: IC50 = 13300 nM (pChEMBL 4.880000114440918)
Descriptors: MW 390.52, ALogP 4.94, HBA 5, HBD 2, PSA 75.99, QED 0.56
Compound (SMILES): O=C(Cn1c(=O)oc2ccc(F)cc21)c1ccc2ccccc2c1
InChIKey: ZYZYOGYFCLTNCX-UHFFFAOYSA-N
Target: Chromodomain Y-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y232
Assay: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis
Measurement: Kd = 20100 nM (pChEMBL 4.699999809265137)
Descriptors: MW 321.31, ALogP 3.77, HBA 4, HBD 0, PSA 52.21, QED 0.54
Compound (SMILES): C[C@H](c1ccc(O)cc1)[C@H](O)N1CCC(Cc2ccccc2)CC1
InChIKey: JOVJMUHKBUFINJ-IERDGZPVSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: Displacement of [3H]ifenprodil from GluN1a/GluN2B (unknown origin) expressed in mouse L(tk-) cell membranes after 120 mins by solid scintillation counting method
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 325.45, ALogP 3.77, HBA 3, HBD 2, PSA 43.7, QED 0.88
Compound (SMILES): COc1cnc(Nc2ccc(N3CCOCC3)cc2)nc1Nc1ccc(C)c(O)c1
InChIKey: HSZFANAUIVGILH-UHFFFAOYSA-N
Target: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99640
Assay: Displacement of (6-FAM)KI(pY)VV from PKMYT1 kinase domain (unknown origin) by fluorescence polarization binding assay
Measurement: IC50 = 9332.54 nM (pChEMBL 5.03000020980835)
Descriptors: MW 407.47, ALogP 3.82, HBA 8, HBD 3, PSA 91.77, QED 0.57
Compound (SMILES): COCCc1cn(Cc2ccc(C(=O)NO)cc2)c2ccccc12
InChIKey: QOOQDKFEHZLJPF-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of tubastatin-Alexa647-tracer binding to recombinant GST-tagged HDAC10 (unknown origin) measured after 1 hr by TR-FRET assay
Measurement: IC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 324.38, ALogP 3, HBA 4, HBD 2, PSA 63.49, QED 0.54
Compound (SMILES): C[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)COCCOCCNC(=O)CCOCCOCCOCCNC(=O)CCc1ccc(C(=C\C=C2\N(CCCCS(=O)(=O)O)c3ccc4c(S(=O)(=O)[O-])cc(S(=O)(=O)O)cc4c3C2(C)C)/C=C/C2=[N+](CCCCS(=O)(=O)O)c3ccc4c(S(=O)(=O)O)cc(S(=O)(=O)O)cc4c3C2(C)C)cc1)P(=O)(O)C[C@@H](CCc1ccccc1)C(=O)O
InChIKey: RUVHVYMIMBVNKN-YQGUEOHTSA-N
Target: Carboxypeptidase A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P15085
Assay: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry
Measurement: Ki = 0.089 nM (pChEMBL 10.050000190734863)
Descriptors: MW 1974.22
Compound (SMILES): CSCC[C@@H]1NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(C)=O)CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C(C)C)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: ILFRUBJWEVVJKE-QZUGYRSRSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 2870.52
Compound (SMILES): C[S+]([O-])c1ccc(-c2cnc3ccc(NC4CCS(=O)(=O)CC4)nn23)cc1
InChIKey: RXCGYHXRJHWFNX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells at holding potential of -90 mV by QPatch clamp method
Measurement: IC50 = 28800 nM (pChEMBL 4.539999961853027)
Descriptors: MW 404.52, ALogP 2.12, HBA 7, HBD 1, PSA 99.42, QED 0.67
Compound (SMILES): CN(C)c1ccc(C(=O)N2CCN(C(=O)c3ccc(-c4ccc5c(N)n[nH]c5c4)cc3)CC2)cc1
InChIKey: OHAKLBJQRKYWCS-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of wild type BCR/ABL (unknown origin) measured after 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 2540 nM (pChEMBL 5.590000152587891)
Descriptors: MW 468.56, ALogP 3.48, HBA 5, HBD 2, PSA 98.56, QED 0.48
Compound (SMILES): Cc1nn(-c2ccccc2)c2c1C(c1cccc(C(F)(F)F)c1)CS(=O)(=O)O2
InChIKey: VUIFQCLGLTVSJF-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 16440 nM (pChEMBL 4.78000020980835)
Descriptors: MW 408.4, ALogP 4.05, HBA 5, HBD 0, PSA 61.19, QED 0.6
Compound (SMILES): CCNC(=O)c1ncc(Nc2ncc(F)c(N3C[C@H]4CC[C@H](C3)N4C(=O)C3CC3)n2)cc1C
InChIKey: ZXBVETHTIGOXIX-IAGOWNOFSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK1/TYK2 signaling pathway in human lymphocytes of whole blood assessed as reduction in IFN-alpha induced STAT3 phosphorylation preincubated for 45 mins followed by IFN-alpha addition and measured measured after 15 mins by FACS assay
Measurement: IC50 = 385 nM (pChEMBL 6.420000076293945)
Descriptors: MW 453.52, ALogP 2.4, HBA 7, HBD 2, PSA 103.35, QED 0.69
Compound (SMILES): CCN1C(=O)CC(SC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)C(C)(C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)C(C)(C)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]2CCCN2C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(C)=O)C(C)C)C(N)=O)C1=O
InChIKey: XBDGNGLSQOFOTQ-BUMIVJFUSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 24.23 nM (pChEMBL 7.619999885559082)
Descriptors: MW 2588.98
Compound (SMILES): CS(=N)(=O)c1ccc(-c2ccc(CNC(=O)Cn3c4c(c5cc(F)ccc53)CCn3nccc3-4)nc2)cc1
InChIKey: ASFKLTLQDLUTBK-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of recombinant full length human TRKA expressed in U2OS cells using Poly(Glu:Tyr) as substrate after 30 mins by scintillation counting assay
Measurement: IC50 <= 0.7 nM (pChEMBL 9.154999732971191)
Descriptors: MW 528.61, ALogP 4.61, HBA 7, HBD 2, PSA 105.66, QED 0.34
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc(C)cc1Oc1ccc2sc(N)nc2c1
InChIKey: CXJSZPACGPCOSU-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LB2
Assay: Agonist activity at human MrgprX1 expressed in HEK293 cells incubated for 2 mins by Fluo4AM dye based FLIPR assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 441.53, ALogP 4.79, HBA 7, HBD 2, PSA 103.54, QED 0.45
Compound (SMILES): O=C(CNc1ccc2oc(=O)ccc2c1)c1ccccc1
InChIKey: NPIBXWJMYNWBHM-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin) using acetylthiocholine iodide as substrate by Ellman's method
Measurement: IC50 = 148 nM (pChEMBL 6.829999923706055)
Descriptors: MW 279.3, ALogP 3.09, HBA 4, HBD 1, PSA 59.31, QED 0.59
Compound (SMILES): O=C(CCc1csc(/C=C/c2ccc(Br)cc2)n1)NO
InChIKey: OSYVKTYZELVKCQ-FPYGCLRLSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using fluorogenic HDAC substrate 3 pre-incubated for 30 mins followed by HDAC developer addition and measured after 15 mins by fluorogenic assay
Measurement: IC50 = 16610 nM (pChEMBL 4.78000020980835)
Descriptors: MW 353.24, ALogP 3.51, HBA 4, HBD 2, PSA 62.22, QED 0.64
Compound (SMILES): CCN(c1cc2oc(-c3ccc(F)cc3)c(C(=O)NC)c2cc1-c1ccc(OC)c(C(=O)NC2(c3ncccn3)CC2)c1)S(C)(=O)=O
InChIKey: OHUDQFHGSHRNJY-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 2a JFH1 NS5B RNA dependent RNA polymerase infected in human HuH7 replicon cells after 3 days by luciferase reporter gene assay
Measurement: EC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 657.72, ALogP 5.27, HBA 8, HBD 2, PSA 143.73, QED 0.21
Compound (SMILES): O=S(=O)(NC1CCN(c2ncnc3c2nc(-c2ccccc2Cl)n3-c2ccc(Cl)cc2)CC1)c1ccc(F)cc1
InChIKey: SEIWOXCZYWIJGL-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]-CP55940 from human CB1 receptor expressed in CHO cell membranes
Measurement: Ki = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 597.5, ALogP 5.88, HBA 7, HBD 1, PSA 93.01, QED 0.26
Compound (SMILES): CCCOc1cccc(C(=O)NNS(=O)(=O)c2ccc3ccccc3c2)c1
InChIKey: LBOUTYQAWHOGBB-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6A (SINGLE PROTEIN), Homo sapiens
UniProt: Q92794
Assay: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 384.46, ALogP 3.25, HBA 4, HBD 2, PSA 84.5, QED 0.61
Compound (SMILES): O=C(Nc1cccc(C2CCCN(c3ncnc4[nH]ccc34)C2)c1)Nc1ccccc1N1CCCCC1
InChIKey: NSVAODWRRXRPHA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: In Vitro BTK Kinase Assay: The purpose of the BTK in vitro assay is to determine compound potency against BTK through the measurement of IC50. Compound inhibition is measured after monitoring the amount of phosphorylation of a fluorescein-labeled polyGAT peptide (Invitrogen PV3611) in the presence of active BTK enzyme (Upstate 14-552), ATP, and inhibitor. The BTK kinase reaction was done in a black 96 well plate (costar 3694). For a typical assay, a 24 μL aliquot of a ATP/peptide master mix (final concentration; ATP 10 μM, polyGAT 100 nM) in kinase buffer (10 mM Tris-HCl pH 7.5, 10 mM MgCl2, 200 μM Na3PO4, 5 mM DTT, 0.01% Triton X-100, and 0.2 mg/ml casein) is added to each well. Next, 1 μL of a 4-fold, 40× compound titration in 100% DMSO solvent is added, followed by adding 15 uL of BTK enzyme mix in 1× kinase buffer (with a final concentration of 0.25 nM). The assay is incubated for 30 minutes before being stopped with 28 μL of a 50 mM EDTA solution. Aliquots (5 μL) of the kinase reaction are transferred to a low volume white 384 well plate (Corning 3674), and 5 μL of a 2× detection buffer (Invitrogen PV3574, with 4 nM Tb-PY20 antibody, Invitrogen PV3552) is added. The plate is covered and incubated for 45 minutes at room temperature. Time resolved fluorescence (TRF) on Molecular Devices M5 (332 nm excitation; 488 nm emission; 518 nm fluorescein emission) is measured. IC50 values are calculated using a four parameter fit with 100% enzyme activity determined from the DMSO control and 0% activity from the EDTA control.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 495.63, ALogP 5.98, HBA 5, HBD 3, PSA 89.18, QED 0.32
Compound (SMILES): NS(=O)(=O)c1cccc(Nc2nc(NCc3ccccc3)c3ccccc3n2)c1
InChIKey: AWVQNXPWVWEELS-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5 using [3H]cGMP as substrate incubated for 10 mins by liquid scintillation counter analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 405.48, ALogP 3.63, HBA 6, HBD 3, PSA 110, QED 0.45
Compound (SMILES): CN(C)C(=O)c1cc2cnc(Nc3ccc(C(=O)NCCCCCCN=C=S)cc3F)nc2n1C1CCCC1
InChIKey: NOGROWIFEYWZNS-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of recombinant full-length human CDK9/cyclinT1 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC peptide as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 551.69, ALogP 5.52, HBA 8, HBD 2, PSA 104.51, QED 0.17
Compound (SMILES): COc1ccc(CC(=O)O)c(NC(=O)c2ccc(Cc3c[nH]c4nc(N)[nH]c(=O)c34)cc2)c1
InChIKey: UOZOJZZNBFZRTI-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Cryptosporidium hominis
UniProt: A0A0S4TER9
Assay: Inhibition of recombinant Cryptosporidium hominis TS-DHFR expresssed in Escherichia coli PA414 using dUMP and 5,10-methylenetetrahydrofolate as substrate by spectrometry
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 447.45, ALogP 2.31, HBA 6, HBD 5, PSA 163.19, QED 0.29