lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCCCc1cc(O)c2c(c1)OC(C)(C)[C@H]1CCC(C)=C[C@@H]21
InChIKey: CYQFCXCEBYINGO-SJORKVTESA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MAGL (unknown origin) in human U-937 cells using [ethanolamine-1-3H]AEA as substrate preincubated for 30 mins followed by substrate addition measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 314.47, ALogP 5.74, HBA 2, HBD 1, PSA 29.46, QED 0.57
Compound (SMILES): Cc1nc2c(cnn2-c2csc(C(=O)NC3COC3)c2)cc1Nc1c(F)cccc1Cl
InChIKey: KDMADGZAPDHVHE-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) by titration method
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 457.92, ALogP 4.46, HBA 7, HBD 2, PSA 81.07, QED 0.46
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(C3CCN(C(=O)c4cccnn4)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: UVXCGYVEUGYYNC-JBACZVJFSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Activity Assay: Activity Against Tyro3 Tyrosine Kinase.
Measurement: IC50 = 275 nM (pChEMBL 6.559999942779541)
Descriptors: MW 491.64, ALogP 4.32, HBA 8, HBD 2, PSA 109.06, QED 0.51
Compound (SMILES): O=C(NO)c1ccc(CSc2nnc(-c3ccncc3)n2-c2ccccc2)cc1
InChIKey: BOPVWFFDSBZXNO-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of FAK (unknown origin) by FRET-based Z'-Lyte assay
Measurement: IC50 = 22400 nM (pChEMBL 4.650000095367432)
Descriptors: MW 403.47, ALogP 3.74, HBA 7, HBD 2, PSA 92.93, QED 0.29
Compound (SMILES): O=C1CCc2cc(C(=O)CCCN3CCN(c4ccccn4)CC3)ccc2N1
InChIKey: NFCAJYXEMNIWPF-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human dopamine D4 receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 407.38 nM (pChEMBL 6.389999866485596)
Descriptors: MW 378.48, ALogP 2.75, HBA 5, HBD 1, PSA 65.54, QED 0.78
Compound (SMILES): COc1ccc(CC(=O)Nc2cc(C3CCC3)[nH]n2)cc1
InChIKey: PFCAHEMJANLCHH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Binding affinity to CDK9 (unknown origin)
Measurement: Kd = 1065 nM (pChEMBL 5.96999979019165)
Descriptors: MW 285.35, ALogP 2.87, HBA 3, HBD 2, PSA 67.01, QED 0.89
Compound (SMILES): CC(C)(C)Oc1cc(CCC(C)(C)N2Cc3ccc(S(C)(=O)=O)cc3C2)ccc1O
InChIKey: ISQAPFMBJFZOLG-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Radioligand Binding Assay: Radioligand binding assays for Sigma-1 receptors and Sigma-2 receptors were carried out by a commercial contract research organization. For Sigma-1 binding, various concentrations of test compounds from 100 μM to 1 nM were used to displace 8 nM [3H](+)pentazocine from endogenous receptors on Jurkat cell membranes (Ganapathy M E et al. 1991, J Pharmacol. Exp. Ther. 289:251-260). 10 μM Haloperidol was used to define non-specific binding. For Sigma-2 receptors various concentrations of test compounds from 100 μM to 1 nM were used to displace 5 nM [3H] 1,3-Di-(2-tolyl)guanidine from endogenous receptors on membranes from rat cerebral cortex in the presence of 300 nM (+)pentazocine to mask Sigma-1 receptors. (Bowen W D, et al. 1993, Mol. Neuropharmcol 3:117-126). 10 μM Haloperidol was used to define non-specific binding. Reactions were terminated by rapid filtration through Whatman GF/C filters using a Brandel 12R cell harvester followed by two washes with ice-cold buffer. Radioactivity on the dried filter discs was measured using a liquid scintillation analyzer (Tri-Carb 2900TR; PerkinElmer Life and Analytical Sciences). The displacement curves were plotted and the Ki values of the test ligands for the receptor subtypes were determined using GraphPad Prism (GraphPad Software Inc., San Diego, Calif.). The percentage specific binding was determined by dividing the difference between total bound (disintegrations per minute) and nonspecific bound (disintegrations per minute) by the total bound (disintegrations per minute).
Measurement: Ki = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 431.6, ALogP 4.7, HBA 5, HBD 1, PSA 66.84, QED 0.72
Compound (SMILES): CCCN(CCCCOc1ccc2ccc(=O)[nH]c2c1)CC1CC1c1cccc(Cl)c1Cl
InChIKey: OSXVNRDDXPNSDP-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing GFP2-beta-arrestin2 assessed as beta-arrestin2 recruitment preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 97.72 nM (pChEMBL 7.010000228881836)
Descriptors: MW 473.44, ALogP 6.51, HBA 3, HBD 1, PSA 45.33, QED 0.32
Compound (SMILES): CC(Oc1cc(Cl)ccc1Cl)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: YREDDRFGDDZWFS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Binding affinity to human 5HT2A receptor expressed in CHO-K1 cells assessed as inhibition constant incubated for 1 hr radioligand binding assay
Measurement: Ki = 355 nM (pChEMBL 6.449999809265137)
Descriptors: MW 383.28, ALogP 2.65, HBA 7, HBD 1, PSA 80.4, QED 0.87
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NCC(C)CCCc1ccccc1
InChIKey: TYUKINNXLNULMD-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human D2L receptor expressed in HEK293T cells co-expressing CRE-Luc incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 588.84 nM (pChEMBL 6.230000019073486)
Descriptors: MW 416.6, ALogP 3.24, HBA 4, HBD 4, PSA 118.42, QED 0.27
Compound (SMILES): C/C=C1/CN2CC[C@@]34c5ccccc5N(C)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: HAGBWVNSVWLTKY-ZFWLQQAWSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human mu opioid receptor expressed in CHO-K1 cells by radioligand binding assay
Measurement: Ki = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 366.46, ALogP 2.31, HBA 5, HBD 0, PSA 42.01, QED 0.56
Compound (SMILES): CNC(=O)C(C1CCOC1)N(CC(c1ccccc1)c1ccccc1)C(=O)c1cc(C)c(=O)n(C)c1
InChIKey: DNDOVJOKEDNARH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from 6His-tagged BRD4 BD2/BD1 Y97A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 487.6, ALogP 3.12, HBA 5, HBD 1, PSA 80.64, QED 0.53
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NC(C)c1ccco1
InChIKey: MZDWSPIRGJHBII-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Agonist activity at human histamine H2 receptor expressed in HEK293T cells co-expressing ELucC by beta arrestin2 recruitment assay
Measurement: EC50 = 234.42 nM (pChEMBL 6.630000114440918)
Descriptors: MW 350.45, ALogP 1.93, HBA 5, HBD 4, PSA 131.56, QED 0.36
Compound (SMILES): NC(=O)c1ccc2c(c1)CCCN2Cc1ccc(C(=O)NO)cc1
InChIKey: ZRFMDXMQBRKKOA-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human HDAC4 using Boc-Lys(TFA)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence-based assay
Measurement: IC50 = 454 nM (pChEMBL 6.340000152587891)
Descriptors: MW 325.37, ALogP 1.86, HBA 4, HBD 3, PSA 95.66, QED 0.59
Compound (SMILES): COc1ccc(Cl)cc1C1CC1CNCCCOc1ccc2ccc(=O)[nH]c2c1
InChIKey: SREQHVVABVWCKT-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing GFP2-beta-arrestin2 assessed as beta-arrestin2 recruitment preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 15.14 nM (pChEMBL 7.820000171661377)
Descriptors: MW 412.92, ALogP 4.35, HBA 4, HBD 2, PSA 63.35, QED 0.51
Compound (SMILES): Nc1nc2cc(-c3nn(CCCCCCC(=O)NO)c4ncnc(N)c34)ccc2o1
InChIKey: FKVKATMLAUBQFC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin) using U-Light-4E-BP1 peptide as a substrate in the presence of ATP incubated for 30 mins by Lance ultra assay
Measurement: IC50 = 7.67 nM (pChEMBL 8.119999885559082)
Descriptors: MW 410.44, ALogP 2.25, HBA 10, HBD 4, PSA 171, QED 0.19
Compound (SMILES): CC(C)(Oc1cccc(N2CCC[C@@H](C(=O)N(Cc3ccc(-c4cn[nH]c4)cc3)C3CC3)C2)c1)C(=O)N1CCNCC1.Cl
InChIKey: PQRRIGABHUYXRQ-UFTMZEDQSA-N
Target: Catenin beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35222
Assay: Inhibition of beta-catenin (unknown origin) transfected in HEK293 cells cotransfected with pCMV-RL assessed as reduction in luciferase activity measured after 24 hrs by TOPFlash luciferase reporter assay
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 570.74, ALogP 4.07, HBA 6, HBD 2, PSA 93.8, QED 0.4
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NCC(C)C1CCCCC1
InChIKey: PMBDKZARCOUAFU-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Agonist activity at human histamine H2 receptor expressed in HEK293T cells co-expressing ELucC by beta arrestin2 recruitment assay
Measurement: EC50 = 223.87 nM (pChEMBL 6.650000095367432)
Descriptors: MW 380.56, ALogP 2.8, HBA 4, HBD 4, PSA 118.42, QED 0.33
Compound (SMILES): CC(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](CCCCN)C(N)=O
InChIKey: VFHJSFDHAZMQQA-NAGBALJGSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 767.93, ALogP 4.08, HBA 6, HBD 7, PSA 201.3, QED 0.06
Compound (SMILES): O=C1NC(=O)C(CCC(=O)N2CCN(c3cccc(Cl)c3)CC2)(c2ccccc2)N1
InChIKey: BLPSVYQVAGCHMF-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: In Vitro Assay: MMP-13(2): The basis for the assay is the cleavage of the substrate 520 MMP-fret substrate XV (Anaspec, Catalog #: AS-60582-01) by human MMP13 (Chemicon, Cat # CC068). For the dose response (10 point), 4 uL of a dilution series of compound (2 mM highest concentration, 1/5 dilution in DMSO further diluted 1 in 10 in water, corresponding to a final highest concentration of 20 uM), is transferred to 384 well Fluotrac 200 plate (Greiner, cat #781076) and incubated at room temperature for 30 min with a 26 uL buffer solution (50 mM Tris pH7.5, 150 mM NaCl, 10 mM CaCl2, 0.05% CHAPS, 5 uM ZnCl2) containing MMP13 (6.25 10-6 ug/uL) (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration). The reaction is initiated by adding to the assay plate 520 MMP-fret substrate XV (10 uL, 4 uM) in the same buffer. Finally, the fluorescence is read on the Envision (Perkin Elmer) after an incubation of 60 min at room temperature (Excitation 485 nm, Emission 530).
Measurement: IC50 = 2150 nM (pChEMBL 5.670000076293945)
Descriptors: MW 426.9, ALogP 2.5, HBA 4, HBD 2, PSA 81.75, QED 0.72
Compound (SMILES): N=C(NO)c1ccc2nc(-c3cccc(-c4cn5ccccc5n4)c3)[nH]c2c1
InChIKey: WEMGUFBETKXSRV-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of C-terminal His-tagged human recombinant full length HDAC3 (1 to 428 residues)/N-terminal GST-tagged human recombinant NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells assessed as reduction in 7-amino-4-methylcoumarin release using fluorogenic HDAC substrate 3 measured every 5 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 368.4, ALogP 3.85, HBA 5, HBD 4, PSA 102.09, QED 0.22
Compound (SMILES): Nc1ncnc2c1c(-c1cnc3[nH]ccc3c1)nn2CCCCCCCCC(=O)NO
InChIKey: ARDWVIIRTDNEHG-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Ac-peptide as a substrate pretreated for 15 mins followed by substrate addition
Measurement: IC50 = 9.54 nM (pChEMBL 8.020000457763672)
Descriptors: MW 422.49, ALogP 3.19, HBA 8, HBD 4, PSA 147.63, QED 0.17
Compound (SMILES): CNC(=O)C(C)N(CC(c1ccccc1)c1ccccn1)C(=O)c1cc(C)c(=O)n(C)c1
InChIKey: NDGVSZDTUKRHOH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from 6His-tagged BRD4 BD1/BD2 Y390A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 432.52, ALogP 2.5, HBA 5, HBD 1, PSA 84.3, QED 0.62
Compound (SMILES): CC1(CCCN2CCN(c3ccccn3)CC2)Cc2cc(Cl)ccc2C1=O
InChIKey: AKXPLUFJRRUGNE-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human dopamine D4 receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 47.86 nM (pChEMBL 7.320000171661377)
Descriptors: MW 383.92, ALogP 4.08, HBA 4, HBD 0, PSA 36.44, QED 0.78
Compound (SMILES): CN1CCN(Cc2ccc(OCCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2)CC1
InChIKey: NZDANPPRKVYGPL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Binding affinity to 5-HT6 receptor (unknown origin)
Measurement: Ki = 122.7 nM (pChEMBL 6.909999847412109)
Descriptors: MW 480.63, ALogP 4.75, HBA 6, HBD 0, PSA 44.98, QED 0.41
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(C3CCN(C(=O)c4ncccn4)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: RGFGVLQJEABYNU-JBACZVJFSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Activity Assay: Activity Against Tyro3 Tyrosine Kinase.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 491.64, ALogP 4.32, HBA 8, HBD 2, PSA 109.06, QED 0.51
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc4scc(-c5cccc(NS(C)(=O)=O)c5)c4n3)cc2)CC1
InChIKey: MQMVBXQAIMTOTQ-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of FAK (unknown origin)
Measurement: IC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 508.67, ALogP 4.62, HBA 8, HBD 2, PSA 90.46, QED 0.38
Compound (SMILES): CC(C)n1cc(C(=O)Nc2ccc(Oc3cc(NC(=O)N4CCC(N5CCN(C)CC5)CC4)ncn3)cc2)c(=O)n(-c2ccc(F)cc2)c1=O
InChIKey: QPIHEOATRHIZAP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Mus musculus
UniProt: Q60805
Assay: Inhibition of Mer in mouse BaF3 cells
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 685.76, ALogP 3.8, HBA 11, HBD 2, PSA 146.93, QED 0.28
Compound (SMILES): CCc1nc(-c2ccc3c(c2)CC[C@H]3NC(=O)c2cnn(C)c2)no1
InChIKey: IOVAZWDIRCRMTM-OAHLLOKOSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes assessed as bufuralol 1'-hydroxylation reaction incubated for 30 mins in presence of NADP by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 337.38, ALogP 2.45, HBA 6, HBD 1, PSA 85.84, QED 0.79
Compound (SMILES): FC(F)(F)c1cccc(Nc2nc(Nc3ccc(-c4ccsc4)cn3)ncc2Cl)c1
InChIKey: WRTIVQWHCXIVQC-UHFFFAOYSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of Cathepsin L (unknown origin) using Z-Leu-Arg-AMC as substrate pretreated for 60 mins followed by substrate addition incubated for 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.87, ALogP 6.76, HBA 6, HBD 2, PSA 62.73, QED 0.35
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(NCC3CC3)c3ccccc3)ccc2F)c1
InChIKey: MCLZOCFEIKBMBA-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as substrate measured after 5 mins by microplate reader analysis
Measurement: IC50 = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 537.56, ALogP 5.83, HBA 5, HBD 3, PSA 84.97, QED 0.23
Compound (SMILES): C[C@@H]1CC[C@@H](Nc2nc(NC(C)(C)C)ncc2C(N)=O)C[C@H]1O
InChIKey: QBBRJRLJWXRSHQ-CKYFFXLPSA-N
Target: Mitogen-activated protein kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P45984
Assay: Inhibition of JNK2 (unknown origin)
Measurement: IC50 = 45.8 nM (pChEMBL 7.340000152587891)
Descriptors: MW 321.43, ALogP 1.75, HBA 6, HBD 4, PSA 113.16, QED 0.67
Compound (SMILES): CC(C(=O)Nc1ccc(Cl)cc1)N1CCC2C(CCCN2c2ccnc(C(F)(F)F)n2)C1
InChIKey: DAQDDNYIMPDZDJ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human whole blood
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 467.92, ALogP 4.47, HBA 5, HBD 1, PSA 61.36, QED 0.72
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(C3CCN(C(=O)C4CCOCC4)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: OHFCYJVNUVCECF-VJBMBRPKSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Activity Assay: Activity Against Tyro3 Tyrosine Kinase.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 497.68, ALogP 4.64, HBA 7, HBD 2, PSA 92.51, QED 0.58
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)c(N)c3)nc3[nH]ccc23)c1
InChIKey: LWZHQZHKOWYTJH-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR C797S mutant (unknown origin) pretreated with substrate for 10 mins followed by ATP addition measured after 60 mins by mobility shift assay
Measurement: IC50 = 0.76 nM (pChEMBL 9.119999885559082)
Descriptors: MW 484.56, ALogP 3.95, HBA 8, HBD 4, PSA 124.43, QED 0.23
Compound (SMILES): Nc1ccc(CCCCN2CCN(c3ccccn3)CC2)cc1
InChIKey: PGTMRNBGCGSJFJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 310.44, ALogP 2.81, HBA 4, HBD 1, PSA 45.39, QED 0.66
Compound (SMILES): CCCCCc1cc(O)c2c(c1)OC(C)(C)[C@H]1CCC(C)=C[C@@H]21
InChIKey: CYQFCXCEBYINGO-SJORKVTESA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of human ABHD6 transfected in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 = 39800 nM (pChEMBL 4.400000095367432)
Descriptors: MW 314.47, ALogP 5.74, HBA 2, HBD 1, PSA 29.46, QED 0.57
Compound (SMILES): Cc1nc2c(cnn2-c2csc(C(=O)NC3COC3)c2)cc1Nc1c(F)cccc1Cl
InChIKey: KDMADGZAPDHVHE-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) by titration method
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 457.92, ALogP 4.46, HBA 7, HBD 2, PSA 81.07, QED 0.46
Compound (SMILES): O=C1CCc2cc(C(=O)CCCN3CCN(c4ccccn4)CC3)ccc2N1
InChIKey: NFCAJYXEMNIWPF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 47.3 nM (pChEMBL 7.329999923706055)
Descriptors: MW 378.48, ALogP 2.75, HBA 5, HBD 1, PSA 65.54, QED 0.78
Compound (SMILES): CC(C)(C)Oc1cc(CCC(C)(C)N2Cc3ccc(S(C)(=O)=O)cc3C2)ccc1O
InChIKey: ISQAPFMBJFZOLG-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Radioligand Binding Assay: Radioligand binding assays for Sigma-1 receptors and Sigma-2 receptors were carried out by a commercial contract research organization. For Sigma-1 binding, various concentrations of test compounds from 100 μM to 1 nM were used to displace 8 nM [3H](+)pentazocine from endogenous receptors on Jurkat cell membranes (Ganapathy M E et al. 1991, J Pharmacol. Exp. Ther. 289:251-260). 10 μM Haloperidol was used to define non-specific binding. For Sigma-2 receptors various concentrations of test compounds from 100 μM to 1 nM were used to displace 5 nM [3H] 1,3-Di-(2-tolyl)guanidine from endogenous receptors on membranes from rat cerebral cortex in the presence of 300 nM (+)pentazocine to mask Sigma-1 receptors. (Bowen W D, et al. 1993, Mol. Neuropharmcol 3:117-126). 10 μM Haloperidol was used to define non-specific binding. Reactions were terminated by rapid filtration through Whatman GF/C filters using a Brandel 12R cell harvester followed by two washes with ice-cold buffer. Radioactivity on the dried filter discs was measured using a liquid scintillation analyzer (Tri-Carb 2900TR; PerkinElmer Life and Analytical Sciences). The displacement curves were plotted and the Ki values of the test ligands for the receptor subtypes were determined using GraphPad Prism (GraphPad Software Inc., San Diego, Calif.). The percentage specific binding was determined by dividing the difference between total bound (disintegrations per minute) and nonspecific bound (disintegrations per minute) by the total bound (disintegrations per minute).
Measurement: Ki = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 431.6, ALogP 4.7, HBA 5, HBD 1, PSA 66.84, QED 0.72
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NCC(C)CCCc1ccccc1
InChIKey: TYUKINNXLNULMD-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3 receptor expressed in HEK293T cells co-expressing CRE-Luc incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 56.23 nM (pChEMBL 7.25)
Descriptors: MW 416.6, ALogP 3.24, HBA 4, HBD 4, PSA 118.42, QED 0.27
Compound (SMILES): C/C=C1/CN2CC[C@@]34c5ccccc5N(C)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: HAGBWVNSVWLTKY-ZFWLQQAWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from human kappa opioid receptor expressed in U2OS cells by radioligand binding assay
Measurement: Ki = 2250 nM (pChEMBL 5.650000095367432)
Descriptors: MW 366.46, ALogP 2.31, HBA 5, HBD 0, PSA 42.01, QED 0.56
Compound (SMILES): Cc1cc(-c2cc(-c3cc(S(=O)(=O)NCC(C)(C)O)ccc3C)cnc2N)on1
InChIKey: PJSOHQYOAVQLMP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Lanthascreen Kinase Binding Assay for mTOR (G): Binding Assays are based on the binding and displacement of an Alexa Fluor 647-labeled, ATP-competitive kinase inhibitors to the kinase of interest. Invitrogen's Kinase Tracers have been developed to address a wide range of kinase targets and are based on ATP-competitive kinase inhibitors, making them suitable for detection of any compounds that bind to the ATP site or to an allosteric site altering the conformation of the ATP site.In the Lanthascreen kinase binding assay, the donor (Eu3+-anti-GST (glutathione S-transferase) antibody) is excited at 340 nm and will transfer its energy to the acceptor (Alexa Fluor 647-labeled ATP-competitive kinase inhibitor=Tracer-314). The emission from the Tracer-314 (Alexa Fluor 647 inhibitor) can be monitored with a filter centered at 665 nm because it is located between the emission peaks of the donor, which is measured at 615/620 nm. The binding of both, the Tracer-314 and Eu3+-anti-GST antibody, to the kinase results in a high degree of FRET from the Eu3+-donor fluorophore to the Alexa-Fluor 647-acceptor fluorophore on the Tracer-314. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET.50 nL of compound dilutions were dispensed onto white 384-well small volume polystyrene plate. Then 5 ul of GST-mTOR and Europium-anti-GST antibody followed by 5 ul of tracer-314 (final assay volume 10 ul) are incubated at RT. The standard reaction buffer for the Lanthascreen kinase binding assay contained 50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM EGTA, 0.01% Pluronic F-127. Plates are read 60 mins later in a Synergy2 reader using an integration time of 0.2 microseconds and a delay of 0.1 microseconds.To calculate the emission ratio, the signal emitted at 665 nm from the acceptor (Alexa Fluor 647-labeled Tracer-314) is divided by the signal emitted at 620 nm from the donor (Eu3+ anti-GST antibody).Control for the 0% inhibition was given by the solvent vehicle of the compounds (90% DMSO in H2O). Control for the relative 100% inhibition was performed by adding 10 uM in the mix containing GST-mTOR and Europium anti-GST antibody. An additional control for the absolute 0% inhibition is given by Eu3+ anti-GST antibody without GST-mTOR. Standard compounds for the lipid kinase panel profiling were used as a reference and included in all assay plates in the form of 8 dilution points.
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 416.5, ALogP 2.65, HBA 7, HBD 3, PSA 131.34, QED 0.56
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NC(C)c1ccco1
InChIKey: MZDWSPIRGJHBII-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human D2L receptor expressed in HEK293T cells co-expressing CRE-Luc incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 1698.24 nM (pChEMBL 5.769999980926514)
Descriptors: MW 350.45, ALogP 1.93, HBA 5, HBD 4, PSA 131.56, QED 0.36
Compound (SMILES): NC(=O)c1ccc2c(c1)CCCN2Cc1ccc(C(=O)NO)cc1
InChIKey: ZRFMDXMQBRKKOA-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant human HDAC5 using Boc-Lys(TFA)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence-based assay
Measurement: IC50 = 276 nM (pChEMBL 6.559999942779541)
Descriptors: MW 325.37, ALogP 1.86, HBA 4, HBD 3, PSA 95.66, QED 0.59
Compound (SMILES): CC1(CC(CO)C(=O)N2CCN(c3cc(Cl)cc(Cl)c3)CC2)NC(=O)NC1=O
InChIKey: LHKXLEZLEFHFJV-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: In Vitro Assay: MMP2: Protocol 2: The basis for the assay is the cleavage of the substrate 390 MMP FRET substrate I (Anaspec, Catalog n#: AS-27076) by human MMP2 (R&D SYSTEMS INC., Cat #902-MP).For the dose response (10 point), 4 μL of a dilution series of compound (2 mM highest concentration, 1/5 dilution in DMSO further diluted 1 in 10 in water, corresponding to a final highest concentration of 20 μM), is transferred to 384 well Fluotrac 200 plate (Greiner, cat #781076) and incubated at room temperature for 30 min with a 26 μL buffer solution (45 mM Tris pH 7.5, 9 mM CaCl2, 135 mM NaCl, 0.045% Brij35) containing MMP2 (0.03 ng/L) (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration).The reaction is initiated by adding to the assay plate 390 MMP FRET substrate I (10 μL, 2.5 μM, Anaspec) in the same buffer.Finally, the fluorescence is read on the Envision (Perkin Elmer) after an incubation of 30 min at room temperature (Excitation 485 nm, Emission 530).
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 429.3, ALogP 1.24, HBA 5, HBD 3, PSA 101.98, QED 0.61
Compound (SMILES): Nc1nc2cc(-c3nn(CCCCCCC(=O)NO)c4ncnc(N)c34)ccc2o1
InChIKey: FKVKATMLAUBQFC-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using Ac-peptide as a substrate pretreated for 15 mins followed by substrate addition
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 410.44, ALogP 2.25, HBA 10, HBD 4, PSA 171, QED 0.19
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NCC(C)C1CCCCC1
InChIKey: PMBDKZARCOUAFU-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human D2L receptor expressed in HEK293T cells co-expressing CRE-Luc incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 263.03 nM (pChEMBL 6.579999923706055)
Descriptors: MW 380.56, ALogP 2.8, HBA 4, HBD 4, PSA 118.42, QED 0.33
Compound (SMILES): N=C(NO)c1ccc2nc(-c3cccc(-c4cn5ccccc5n4)c3)[nH]c2c1
InChIKey: WEMGUFBETKXSRV-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of N-terminal GST-tagged/C-terminal His-tagged human recombinant HDAC4 (627 to 1084 residues) expressed in baculovirus-infected Sf9 cells assessed as reduction in 7-amino-4-methylcoumarin release measured every 5 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 368.4, ALogP 3.85, HBA 5, HBD 4, PSA 102.09, QED 0.22
Compound (SMILES): CNC(=O)C(C)N(CC(c1ccccc1)c1ccccn1)C(=O)c1cc(C)c(=O)n(C)c1
InChIKey: NDGVSZDTUKRHOH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from 6His-tagged BRD4 BD1/BD2 Y390A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 432.52, ALogP 2.5, HBA 5, HBD 1, PSA 84.3, QED 0.62
Compound (SMILES): CC1(CCCN2CCN(c3ccccn3)CC2)Cc2cc(Cl)ccc2C1=O
InChIKey: AKXPLUFJRRUGNE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 0.74 nM (pChEMBL 9.130000114440918)
Descriptors: MW 383.92, ALogP 4.08, HBA 4, HBD 0, PSA 36.44, QED 0.78
Compound (SMILES): CN1CCN(Cc2ccc(OCCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2)CC1
InChIKey: NZDANPPRKVYGPL-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Binding affinity to alpha1 adrenoceptor (unknown origin)
Measurement: Ki = 353.6 nM (pChEMBL 6.449999809265137)
Descriptors: MW 480.63, ALogP 4.75, HBA 6, HBD 0, PSA 44.98, QED 0.41
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc4scc(-c5cccc(NS(C)(=O)=O)c5)c4n3)cc2)CC1
InChIKey: MQMVBXQAIMTOTQ-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Inhibition of CK2alpha1 (unknown origin)
Measurement: IC50 = 13.9 nM (pChEMBL 7.860000133514404)
Descriptors: MW 508.67, ALogP 4.62, HBA 8, HBD 2, PSA 90.46, QED 0.38
Compound (SMILES): CCc1nc(-c2ccc3c(c2)CC[C@H]3NC(=O)c2cnn(C)c2)no1
InChIKey: IOVAZWDIRCRMTM-OAHLLOKOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes assessed as midazolam 1'-hyrozylation reaction incubated for 30 mins in presence of NADP by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 337.38, ALogP 2.45, HBA 6, HBD 1, PSA 85.84, QED 0.79
Compound (SMILES): FC(F)(F)c1cccc(Nc2nc(Nc3ccc(-c4ccsc4)cn3)ncc2Cl)c1
InChIKey: WRTIVQWHCXIVQC-UHFFFAOYSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of Cathepsin S (unknown origin) using MCA-Arg-Pro-Lys-Pro-Val-Glu-NVAL-Trp-Arg-Lys-(DNP)-NH2 as substrate pretreated for 60 mins followed by substrate addition incubated for 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.87, ALogP 6.76, HBA 6, HBD 2, PSA 62.73, QED 0.35
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(NCC3CC3)c3ccccc3)ccc2F)c1
InChIKey: MCLZOCFEIKBMBA-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Plasma Kallikrein Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader (Winooski, Vt., USA). Data were analyzed using SigmaPlot software (Systat Software, Inc., San Jose, Calif., USA) (Four Parameter Logistic Curve). Ki values for the inhibitors were determined using the Cheng-Prusoff equation (Biochem. Pharmacol. 1973, 22, 3099).
Measurement: Ki = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 537.56, ALogP 5.83, HBA 5, HBD 3, PSA 84.97, QED 0.23
Compound (SMILES): C[C@@H]1CC[C@@H](Nc2nc(NC(C)(C)C)ncc2C(N)=O)C[C@H]1O
InChIKey: QBBRJRLJWXRSHQ-CKYFFXLPSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3 (unknown origin)
Measurement: IC50 = 52.2 nM (pChEMBL 7.28000020980835)
Descriptors: MW 321.43, ALogP 1.75, HBA 6, HBD 4, PSA 113.16, QED 0.67
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)c(N)c3)nc3[nH]ccc23)c1
InChIKey: LWZHQZHKOWYTJH-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR L858R/T790M/C797S mutant (unknown origin) pretreated with substrate for 10 mins followed by ATP addition measured after 60 mins by mobility shift assay
Measurement: IC50 = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 484.56, ALogP 3.95, HBA 8, HBD 4, PSA 124.43, QED 0.23
Compound (SMILES): Nc1ccc(CCCCN2CCN(c3ccccn3)CC2)cc1
InChIKey: PGTMRNBGCGSJFJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 13.49 nM (pChEMBL 7.869999885559082)
Descriptors: MW 310.44, ALogP 2.81, HBA 4, HBD 1, PSA 45.39, QED 0.66
Compound (SMILES): CCCCCc1cc(O)c2c(c1)OC(C)(C)[C@H]1CCC(C)=C[C@@H]21
InChIKey: CYQFCXCEBYINGO-SJORKVTESA-N
Target: Lysophosphatidylserine lipase ABHD12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N2K0
Assay: Inhibition of human ABHD12 transfected in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 = 14100 nM (pChEMBL 4.849999904632568)
Descriptors: MW 314.47, ALogP 5.74, HBA 2, HBD 1, PSA 29.46, QED 0.57
Compound (SMILES): Cc1nc2c(cnn2-c2csc(C(=O)NC3COC3)c2)cc1Nc1c(F)cccc1Cl
InChIKey: KDMADGZAPDHVHE-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of human CK1E using KRRRAL[pS]VASLPGL as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 457.92, ALogP 4.46, HBA 7, HBD 2, PSA 81.07, QED 0.46
Compound (SMILES): O=C1CCc2cc(C(=O)CCCN3CCN(c4ccccn4)CC3)ccc2N1
InChIKey: NFCAJYXEMNIWPF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 378.48, ALogP 2.75, HBA 5, HBD 1, PSA 65.54, QED 0.78
Compound (SMILES): CC(C)(C)Oc1cc(CCC(C)(C)N2Cc3ccc(S(C)(=O)=O)cc3C2)ccc1O
InChIKey: ISQAPFMBJFZOLG-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Competitive Radioligand Binding Assay: The affinity of candidate sigma-2 ligand compounds at sigma-1 and sigma-2 receptors was also determined by displacement of different known labeled sigma-2 or sigma-1 ligands. Filtration assays were conducted according the previously published procedure (Xu, et al., 2005). Test compounds were dissolved in N,N-Dimethylformamide (DMF), dimethyl sulfoxide (DMSO) or ethanol and then diluted in 50 mM Tris-HCl pH 7.4 buffer containing 150 mM NaCl and 100 mM EDTA. Membrane homogenates were made from guinea pig brain for sigma-1 binding assay and rat liver for sigma-2 binding assay. Membrane homogenates were diluted with 50 mM Tris-HCl buffer, pH 8.0 and incubated at 25° C. in a total volume of 150 uL in 96 well plates with the radioligand and test compounds with concentrations ranging from 0.1 nM to 10 uM. After incubation was completed, the reactions were terminated by the addition of 150 uL of ice-cold wash buffer (10 mM Tris HCl, 150 mM NaCl, pH 7.4) using a 96 channel transfer pipette (Fisher Scientific, Pittsburgh, Pa.) and the samples harvested and filtered rapidly through 96 well fiber glass filter plate (Millipore, Billerica, Mass.) that had been presoaked with 100 uL of 50 mM Tris-HCl buffer. Each filter was washed four times with 200 uL of ice-cold wash buffer (10 mM Tris-HCl, 150 mM NaCl, pH 7.4). A Wallac 1450 MicroBeta liquid scintillation counter (Perkin Elmer, Boston, Mass.) was used to quantitate the bound radioactivity. The sigma-1 receptor binding assays were conducted using guinea pig brain membrane homogenates (300 ug protein) and 5 nM [3H](+)-pentazocine (34.9 Ci/mmol, Perkin Elmer, Boston, Mass.), incubation time was 90 min at room temperature. Nonspecific binding was determined from samples that contained 10 μM of cold haloperidol. The sigma-2 receptor binding assays were conducted using rat liver membrane homogenates (300 ug protein) and 2 nM sigma-2 highly selective radioligand [3H]RHM-1 only (no other blockers) (America Radiolabeled Chemicals Inc. St. Louis, Mo.), 10 nM [3H]DTG (58.1 Ci/mmol, Perkin Elmer, Boston, Mass.) or 10 nM [3H]Haloperidol (America Radiolabeled Chemicals Inc., St. Louis, Mo.) in the presence of 1 uM (+)-pentazocine to block sigma-1 sites, incubation times were 6 minutes for [3H]RHM-1, 120 min for [3H]DTG and [3H]haloperidol at room temperature. Nonspecific binding was determined from samples that contained 10 uM of cold haloperidol.
Measurement: Ki = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 431.6, ALogP 4.7, HBA 5, HBD 1, PSA 66.84, QED 0.72
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NCC(C)CCCc1ccccc1
InChIKey: TYUKINNXLNULMD-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human histamine D2L receptor receptor expressed in HEK293T cells co-expressing ELucC by beta arrestin2 recruitment assay
Measurement: EC50 = 2951.21 nM (pChEMBL 5.53000020980835)
Descriptors: MW 416.6, ALogP 3.24, HBA 4, HBD 4, PSA 118.42, QED 0.27
Compound (SMILES): C/C=C1/CN2CC[C@@]34c5ccccc5N(C)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: HAGBWVNSVWLTKY-ZFWLQQAWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from human kappa opioid receptor expressed in U2OS cells by radioligand binding assay
Measurement: Ki = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 366.46, ALogP 2.31, HBA 5, HBD 0, PSA 42.01, QED 0.56
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NC(C)c1ccco1
InChIKey: MZDWSPIRGJHBII-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3 receptor expressed in HEK293T cells co-expressing CRE-Luc incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 17.38 nM (pChEMBL 7.760000228881836)
Descriptors: MW 350.45, ALogP 1.93, HBA 5, HBD 4, PSA 131.56, QED 0.36
Compound (SMILES): NC(=O)c1ccc2c(c1)CCCN2Cc1ccc(C(=O)NO)cc1
InChIKey: ZRFMDXMQBRKKOA-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human HDAC7 using Boc-Lys(TFA)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence-based assay
Measurement: IC50 = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 325.37, ALogP 1.86, HBA 4, HBD 3, PSA 95.66, QED 0.59
Compound (SMILES): CC1(CC(CO)C(=O)N2CCN(c3cc(Cl)cc(Cl)c3)CC2)NC(=O)NC1=O
InChIKey: LHKXLEZLEFHFJV-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: In Vitro Assay: MMP2: Protocol 2: The basis for the assay is the cleavage of the substrate 390 MMP FRET substrate I (Anaspec, Catalog n#: AS-27076) by human MMP2 (R&D SYSTEMS INC., Cat #902-MP).For the dose response (10 point), 4 μL of a dilution series of compound (2 mM highest concentration, 1/5 dilution in DMSO further diluted 1 in 10 in water, corresponding to a final highest concentration of 20 μM), is transferred to 384 well Fluotrac 200 plate (Greiner, cat #781076) and incubated at room temperature for 30 min with a 26 μL buffer solution (45 mM Tris pH 7.5, 9 mM CaCl2, 135 mM NaCl, 0.045% Brij35) containing MMP2 (0.03 ng/L) (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration).The reaction is initiated by adding to the assay plate 390 MMP FRET substrate I (10 μL, 2.5 μM, Anaspec) in the same buffer.Finally, the fluorescence is read on the Envision (Perkin Elmer) after an incubation of 30 min at room temperature (Excitation 485 nm, Emission 530).
Measurement: IC50 = 2820 nM (pChEMBL 5.550000190734863)
Descriptors: MW 429.3, ALogP 1.24, HBA 5, HBD 3, PSA 101.98, QED 0.61
Compound (SMILES): Nc1nc2cc(-c3nn(CCCCCCC(=O)NO)c4ncnc(N)c34)ccc2o1
InChIKey: FKVKATMLAUBQFC-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using Ac-peptide as a substrate pretreated for 15 mins followed by substrate addition
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 410.44, ALogP 2.25, HBA 10, HBD 4, PSA 171, QED 0.19
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NCC(C)C1CCCCC1
InChIKey: PMBDKZARCOUAFU-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3 receptor expressed in HEK293T cells co-expressing CRE-Luc incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 43.65 nM (pChEMBL 7.360000133514404)
Descriptors: MW 380.56, ALogP 2.8, HBA 4, HBD 4, PSA 118.42, QED 0.33
Compound (SMILES): N=C(NO)c1ccc2nc(-c3cccc(-c4cn5ccccc5n4)c3)[nH]c2c1
InChIKey: WEMGUFBETKXSRV-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of N-terminal GST-tagged human recombinant full length HDAC5 expressed in baculovirus-infected Sf9 cells assessed as reduction in 7-amino-4-methylcoumarin release measured every 5 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 368.4, ALogP 3.85, HBA 5, HBD 4, PSA 102.09, QED 0.22
Compound (SMILES): CNC(=O)C(C)N(CC(c1ccccc1)c1ccccn1)C(=O)c1cc(C)c(=O)n(C)c1
InChIKey: NDGVSZDTUKRHOH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from 6His-tagged BRD4 BD2/BD1 Y97A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 432.52, ALogP 2.5, HBA 5, HBD 1, PSA 84.3, QED 0.62
Compound (SMILES): CC1(CCCN2CCN(c3ccccn3)CC2)Cc2cc(Cl)ccc2C1=O
InChIKey: AKXPLUFJRRUGNE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 0.7413 nM (pChEMBL 9.130000114440918)
Descriptors: MW 383.92, ALogP 4.08, HBA 4, HBD 0, PSA 36.44, QED 0.78
Compound (SMILES): CN1CCN(Cc2ccc(OCCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2)CC1
InChIKey: NZDANPPRKVYGPL-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Binding affinity to histamine H1 receptor (unknown origin)
Measurement: Ki = 642.4 nM (pChEMBL 6.190000057220459)
Descriptors: MW 480.63, ALogP 4.75, HBA 6, HBD 0, PSA 44.98, QED 0.41
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc4scc(-c5cccc(NS(C)(=O)=O)c5)c4n3)cc2)CC1
InChIKey: MQMVBXQAIMTOTQ-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET (unknown origin)
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 508.67, ALogP 4.62, HBA 8, HBD 2, PSA 90.46, QED 0.38
Compound (SMILES): CCc1nc(-c2ccc3c(c2)CC[C@H]3NC(=O)c2cnn(C)c2)no1
InChIKey: IOVAZWDIRCRMTM-OAHLLOKOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes assessed as testosterone 6-beta-hydroxylation reaction incubated for 30 mins in presence of NADP by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 337.38, ALogP 2.45, HBA 6, HBD 1, PSA 85.84, QED 0.79
Compound (SMILES): FC(F)(F)c1cccc(Nc2nc(Nc3ccc(-c4ccsc4)cn3)ncc2Cl)c1
InChIKey: WRTIVQWHCXIVQC-UHFFFAOYSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of Cathepsin K (unknown origin) using MCA-Arg-Pro-Lys-Pro-Val-Glu-NVAL-Trp-Arg-Lys-(DNP)-NH2 as substrate pretreated for 60 mins followed by substrate addition incubated for 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.87, ALogP 6.76, HBA 6, HBD 2, PSA 62.73, QED 0.35
Compound (SMILES): C[C@@H]1CC[C@@H](Nc2nc(NC(C)(C)C)ncc2C(N)=O)C[C@H]1O
InChIKey: QBBRJRLJWXRSHQ-CKYFFXLPSA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: Inhibition of N-terminal GST-tagged human recombinant full length JNK1 expressed in baculovirus-infected Sf9 cells using p38 substrate and ATP as substrate incubated for 5 hrs by ADP-Glo Kinase assay
Measurement: IC50 = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 321.43, ALogP 1.75, HBA 6, HBD 4, PSA 113.16, QED 0.67
Compound (SMILES): Nc1ccc(CCCCN2CCN(c3ccccn3)CC2)cc1
InChIKey: PGTMRNBGCGSJFJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-Ketanserin from human 5-HT2A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 626 nM (pChEMBL 6.199999809265137)
Descriptors: MW 310.44, ALogP 2.81, HBA 4, HBD 1, PSA 45.39, QED 0.66
Compound (SMILES): Cc1nc2c(cnn2-c2csc(C(=O)NC3COC3)c2)cc1Nc1c(F)cccc1Cl
InChIKey: KDMADGZAPDHVHE-UHFFFAOYSA-N
Target: Epithelial discoidin domain-containing receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q08345
Assay: Inhibition of human DDR1 using KKSRGDYMTMQIG as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 247 nM (pChEMBL 6.610000133514404)
Descriptors: MW 457.92, ALogP 4.46, HBA 7, HBD 2, PSA 81.07, QED 0.46
Compound (SMILES): O=C1CCc2cc(C(=O)CCCN3CCN(c4ccccn4)CC3)ccc2N1
InChIKey: NFCAJYXEMNIWPF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-Ketanserin from human 5-HT2A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 3111 nM (pChEMBL 5.510000228881836)
Descriptors: MW 378.48, ALogP 2.75, HBA 5, HBD 1, PSA 65.54, QED 0.78
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NCC(C)CCCc1ccccc1
InChIKey: TYUKINNXLNULMD-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human histamine D3 receptor receptor expressed in HEK293T cells co-expressing ELucC by beta arrestin2 recruitment assay
Measurement: EC50 = 416.87 nM (pChEMBL 6.380000114440918)
Descriptors: MW 416.6, ALogP 3.24, HBA 4, HBD 4, PSA 118.42, QED 0.27