lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ncc(-c2ccc3ncn([C@H]4CCN(C(=O)C5CC5)C4)c(=O)c3c2)cc1NS(=O)(=O)c1ccc(F)cc1
InChIKey: IXSQTDIQFDKYIS-NRFANRHFSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of P110delta/p85alpha (unknown origin) using L-alpha-phosphatidylinositol as substrate after 40 mins by ATP depletion assay
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 563.61, ALogP 3.59, HBA 8, HBD 1, PSA 123.49, QED 0.36
Compound (SMILES): Oc1cccc(-c2nc(-c3ccc(F)cc3)c(-c3ccnc4[nH]c(-c5ccccc5)cc34)[nH]2)c1
InChIKey: SOTOGKXMOXJSOQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminally GST-tagged EGFR L858R/T790M/C797S triple mutant expressed in baculovirus in Sf9 insect cells preincubated for 20 mins followed by addition of [33P]-ATP measured after 2 hrs by filter-binding method
Measurement: IC50 = 782 nM (pChEMBL 6.110000133514404)
Descriptors: MW 446.49, ALogP 6.8, HBA 3, HBD 3, PSA 77.59, QED 0.28
Compound (SMILES): Clc1cc(NC2=NC[C@@]3(CN4CCC3CC4)O2)ncn1
InChIKey: MPKJZAQJACHFNL-ZDUSSCGKSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Agonist activity at alpha3beta4 nAChR (unknown origin) assessed as increase in calcium influx measured for 2 mins by Fluo-4-AM dye based FLIPR assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 293.76, ALogP 1.39, HBA 6, HBD 1, PSA 62.64, QED 0.79
Compound (SMILES): COc1ccc2c(c1)CC[N+](C)(C)C2.[I-]
InChIKey: YWASSVRYTISOMT-UHFFFAOYSA-M
Target: Nicotinic acetylcholine receptor alpha-4/beta-2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9ERK7
Assay: Antagonist activity at mouse alpha4beta2 nAChR expressed in HEK293 cells assessed as inhibition of (S)-nicotine-induced current response measured up to 90 secs by FMP assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 192.28, ALogP 1.83, HBA 1, HBD 0, PSA 9.23, QED 0.62
Compound (SMILES): CC(=O)Nc1cc(-c2ccc(C)c(S(N)(=O)=O)c2)no1
InChIKey: AWVYVIXIVZZHJY-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase-7 assessed as reduction in enzyme-catalyzed hydration activity using CO2 as substrate preincubated for 15 mins followed substrate addition measured after 10 to 100 sec by phenol red dye based stopped flow assay
Measurement: Ki = 84.5 nM (pChEMBL 7.070000171661377)
Descriptors: MW 295.32, ALogP 1.26, HBA 5, HBD 2, PSA 115.29, QED 0.88
Compound (SMILES): C=CC(=O)Nc1cccc(Cl)c1Nc1ncc(OCc2cc(OC)cc(OC)c2)cn1
InChIKey: TWTPRQANGWFYAF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of His-tagged cytoplasmic recombinant human FGFR4 (781 to 1338 residues) expressed in baculovirus expression system using Tyr 4 peptide as substrate incubated for 1 hr by FRET-based Z'-Lyte assay
Measurement: IC50 = 22.7 nM (pChEMBL 7.639999866485596)
Descriptors: MW 440.89, ALogP 4.59, HBA 7, HBD 2, PSA 94.6, QED 0.47
Compound (SMILES): O=C(O)Cc1ccccc1O[C@H]1CN[C@H](C(=O)O)C1
InChIKey: LPGJYTIZCNSNPB-ZJUUUORDSA-N
Target: Glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19491
Assay: Displacement of (RS)-[3H]AMPA from eGFP-fused recombinant rat full length GluA2 receptor expressed in HEK293T/17 cells by liquid scintillation counting method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 265.26, ALogP 0.51, HBA 4, HBD 3, PSA 95.86, QED 0.72
Compound (SMILES): CN1C(=O)[C@@H](N2CCc3cn(CC4CCS(=O)(=O)CC4)nc3C2=O)COc2ccccc21
InChIKey: IVVSBEQDCAZLFY-SFHVURJKSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Abl(ABL1IHY1) Takeda global kinase panel
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 458.54, ALogP 1.13, HBA 7, HBD 0, PSA 101.81, QED 0.68
Compound (SMILES): N#Cc1ccc(CN2CCC(NC(=O)c3ccc(Cl)cc3Cl)CC2)cc1
InChIKey: PAECAVHKWAMWMA-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent GABA transporter 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P48066
Assay: Inhibition of human GAT3 expresses in tsA201 cells assessed as reduction in [3H]GABA uptake after 3 mins by scintillation counting method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 388.3, ALogP 4.26, HBA 3, HBD 1, PSA 56.13, QED 0.85
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)Nc2cc(Cl)ccc2Cl)cc1
InChIKey: JVTAGZMZWCGBKW-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human recombinant carbonic anhydrase 1 preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 747 nM (pChEMBL 6.130000114440918)
Descriptors: MW 360.22, ALogP 3.28, HBA 3, HBD 3, PSA 101.29, QED 0.78
Compound (SMILES): COc1cc(CNC(=O)C#Cc2cn(Cc3ccc(C(=O)N(C)C)cc3)c(=O)[nH]c2=O)ccc1F
InChIKey: UEGUSCZBRJCYEP-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of C-terminal tagged human recombinant MMP13 catalytic domain expressed in Escherichia coli using (5-FAM/QX) FRET peptide as substrate by fluorescence assay
Measurement: IC50 = 109.65 nM (pChEMBL 6.960000038146973)
Descriptors: MW 478.48, ALogP 1.1, HBA 6, HBD 2, PSA 113.5, QED 0.52
Compound (SMILES): C[C@@H]1CN(C(=O)c2nc(Nc3cc(C4CC4)[nH]n3)c3cc(Cl)ccc3n2)CCN1
InChIKey: RTGFZUPLFGBDKE-LLVKDONJSA-N
Target: Serine/threonine-protein kinase PAK 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P286
Assay: Inhibition of full length recombinant human His-tagged PAK5 (295 to 591 residues) expressed in Baculovirus expression system by Z'-Lyte assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 411.9, ALogP 3.06, HBA 6, HBD 3, PSA 98.83, QED 0.61
Compound (SMILES): CC[C@@H](C)[C@@H]1N=C(c2ccccc2)c2ccccc2N(CCCCC(=O)NO)C1=O
InChIKey: MJFMMWISMNQZBL-VGSWGCGISA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human KDAC8 after 60 mins by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 407.51, ALogP 3.96, HBA 4, HBD 2, PSA 82, QED 0.39
Compound (SMILES): CCc1ccc(C(=O)NCC2NCCc3ccccc32)cc1
InChIKey: NWMKHRAVUSQKEV-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in HEK293 cells assessed as inhibition of forskolin-induced adenylyl cyclase-mediated cAMP accumulation after 30 mins by HTRF assay
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 294.4, ALogP 2.87, HBA 2, HBD 2, PSA 41.13, QED 0.91
Compound (SMILES): Cc1cc(=O)oc2cc(OCc3ccc(Br)cc3)ccc12
InChIKey: FVWAAOMTWGZPCD-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using S-butylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 345.19, ALogP 4.44, HBA 3, HBD 0, PSA 39.44, QED 0.66
Compound (SMILES): COc1ccncc1CCCNCc1ccc2ccc(N)nc2c1
InChIKey: IQPCOMIHSUSLGC-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Inhibition of recombinant human nNOS expressed in Escherichia coli using L-arginine as substrate after 30 secs by hemoglobin capture assay
Measurement: Ki = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 322.41, ALogP 2.94, HBA 5, HBD 2, PSA 73.06, QED 0.65
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CCCN2[C@H]2CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(N)=O)NC(=O)[C@@H]3CSSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)[C@H](Cc4cnc[nH]4)NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC1=O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)NC2=O
InChIKey: CFQRWRHLWMZZET-MVXRHJEXSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Agonist activity at human MC5R expressed in HEK293 cells assessed as increase in cAMP production incubated for 2 hrs by AlphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 3928.57
Compound (SMILES): Cc1cc(CCC(=O)O)ccc1OCc1cccc(Oc2ccccc2)c1
InChIKey: PSWWIJPJQUAYCG-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFA1 receptor expressed in human U2OS cells co-expressing Galpha16 assessed as calcium mobilization by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 3981.07 nM (pChEMBL 5.400000095367432)
Descriptors: MW 362.43, ALogP 5.38, HBA 3, HBD 1, PSA 55.76, QED 0.58
Compound (SMILES): c1ccc2c(c1)CN[C@@H](CN(CCCCNC1CCCCC1)[C@H]1CCCc3cccnc31)C2
InChIKey: AEOPBRLVLXDVLL-IZLXSDGUSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Agonist activity at CXCR4 in human CCRF-CEM cells assessed as induction of Ca2+ flux measured for 90 secs by calcium dye-based fluorescence assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 446.68, ALogP 5.18, HBA 4, HBD 2, PSA 40.19, QED 0.52
Compound (SMILES): O=C(CSc1nnc(Nc2ccccc2)s1)N/N=C/c1ccc(-c2ccc(Cl)cc2Cl)o1
InChIKey: FSGMWEDHXAJYNT-BHGWPJFGSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Competitive inhibition of carbonic anhydrase-2 in human erythrocyte membranes assessed as reduction in H+ release using CO2 as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 0.66 nM (pChEMBL 9.180000305175781)
Descriptors: MW 504.42, ALogP 6.09, HBA 8, HBD 2, PSA 92.41, QED 0.17
Compound (SMILES): Cc1cc(C)cc(C(=O)N(CCCCCC(=O)NO)CC(=O)NC2CCCCC2)c1
InChIKey: FMAYUVHWYXXHME-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli using Z-L-Lys(epsilon-trifluoroacetyl)-AMC as substrate measured after 90 mins by fluorescence assay
Measurement: IC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 417.55, ALogP 3.26, HBA 4, HBD 3, PSA 98.74, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCc3cc(O)c(O)cc3[C@@H]2c2ccccc2)cc1
InChIKey: UBKCMPKCMMEDIG-NRFANRHFSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 424.48, ALogP 2.53, HBA 5, HBD 3, PSA 120.93, QED 0.56
Compound (SMILES): O=S(=O)(NCCCCN1CC=C(c2c[nH]c3ccc(Cl)cc23)CC1)c1ccc(F)cc1
InChIKey: SZFUWLHTOXSEDK-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylspiperone from human D2 receptor expressed in CHO-K1 cells after 60 mins by scintillation counting
Measurement: Ki = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 461.99, ALogP 4.81, HBA 3, HBD 2, PSA 65.2, QED 0.47
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)OCCO3)cc1NC(=O)c1ccc2c(c1)CCCN2
InChIKey: LLTXIVYBCVSFHB-UHFFFAOYSA-N
Target: Pirin (SINGLE PROTEIN), Homo sapiens
UniProt: O00625
Assay: Inhibition of bisamide probe binding to pirin in human SKOV3 cells by SILAC-based quantitative mass spectrometry pull down assay
Measurement: Ki = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 443.5, ALogP 4.63, HBA 5, HBD 3, PSA 88.69, QED 0.55
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(C#N)cc1)c(C)cc(=O)n2C
InChIKey: OHKRNOLZIOHQBM-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Inhibition of human BRPF1 expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 383.43, ALogP 2.53, HBA 6, HBD 1, PSA 101.19, QED 0.75
Compound (SMILES): CC1Cc2ccc(C(=O)Nc3cc(CN4CCN(C)CC4)cc(C(F)(F)F)c3)cc2CN1c1cncnc1
InChIKey: GCCXSOBNEILODC-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Lantha Screen Eu Kinase Activity Assay: The effects of compounds on the kinases DDR1 and DDR2 were assessed by using a Lantha Screen Eu kinase activity assay technology (Invitrogen, USA). Kinase reactions are performed in a 10 uL volume in low-volume 384-well plates. The kinases in reaction buffer consist of 50 mM HEPES pH 7.5, 0.01% BRU-35, 10 mM MgCl2, and 1 mM EGTA, the concentration of Fluorescein-Poly GAT substrate (Invitrogen, USA) in the assay is 100 nM. Kinase reactions were initiated with the addition of 100 nM ATP in the presence of serials of dilutions of compounds. The reactions were allowed to proceed for 1 h at room temperature before a 10 uL preparation of EDTA (20 mM) and Eu-labeled antibody (4 nM) in TR-FRET dilution buffer are added. The final concentration of antibody in the assay well is 2 nM, and the final concentration of EDTA is 10 mM. The plate is allowed to incubate at room temperature for one more hour before the TR-FRET emission ratios of 665 nm/340 nm were acquired on a PerkinElmer EnVision multilabel reader (Perkin-Elmer, Inc.). Data analysis and curve fitting were performed using GraphPad Prism4 software, resulting in the half maximal inhibitory concentration (IC50) shown in table 1. The functional assays of compounds on the kinase activities of c-kit and Abl were determined using the FRET-based Z'-Lyte assay system according to the manufacturer's instructions (Invitrogen, USA). Tyrosine 2 peptide was used as Abl substrate, and Ser/Thr 6 peptide was used as the substrate for c-kit. The reactions were carried out in 384-well plates in a 10 uL of reaction volume with appropriate amount of kinases in 50 mM HEPES (pH 7.5), 10 Mm MgCl2, 1 mM EGTA, and 0.01% Brij-35. The reactions were incubated 1 h at room temperature in the presence of 2 uM of substrate with 10 uM of ATP (for Abl1 assays) or 300 uM of ATP (kit assay) and in the presence of various concentrations of the compounds.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.59, ALogP 4.45, HBA 6, HBD 1, PSA 64.6, QED 0.53
Compound (SMILES): CC1=C(CO)Oc2cccc3c2c1cn3S(=O)(=O)c1ccccc1
InChIKey: GMSIWIKTSBRYGS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Binding affinity to 5HT2A receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 341.39, ALogP 2.99, HBA 5, HBD 1, PSA 68.53, QED 0.8
Compound (SMILES): O=C(C1CCN(c2cc(Oc3ccccc3F)ncn2)CC1)N1CCc2ccccc2C1
InChIKey: OBLWLENBNRYSCO-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Antagonist activity at recombinant human M5 receptor expressed in CHO cells co-expressing Gqi5 by calcium mobilization assay
Measurement: IC50 = 732 nM (pChEMBL 6.130000114440918)
Descriptors: MW 432.5, ALogP 4.21, HBA 5, HBD 0, PSA 58.56, QED 0.62
Compound (SMILES): CC1(C)[C@H](Nc2c(C(N)=O)cnn3cc(-c4ccccc4)cc23)CC[C@]1(C)N
InChIKey: DIFGSGNUHRNWPK-GCJKJVERSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human whole blood assessed as reduction in IL-2 induced IFN-gamma production after 18 hrs by ELISA
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 377.49, ALogP 3.42, HBA 5, HBD 3, PSA 98.44, QED 0.65
Compound (SMILES): O=C1CCc2ccc(OCCCN3CCC(N4CCCC4)CC3)cc2N1
InChIKey: KKRQTLZLQIANNI-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI insect cells using kynuramine as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 19200 nM (pChEMBL 4.71999979019165)
Descriptors: MW 357.5, ALogP 2.9, HBA 4, HBD 1, PSA 44.81, QED 0.8
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cn2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: KYIZIDOGSHFMBO-PPHZAIPVSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 20100 nM (pChEMBL 4.699999809265137)
Descriptors: MW 448.54, ALogP 5.85, HBA 4, HBD 1, PSA 62.66, QED 0.51
Compound (SMILES): CC(C)[C@@]1(C(=O)O)CC[C@@](C)(c2nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3)c3c(N)nccn23)C1
InChIKey: DDAGGHIDQSHQBU-VSGBNLITSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 566.58, ALogP 5.81, HBA 7, HBD 3, PSA 135.5, QED 0.27
Compound (SMILES): C=CC(=O)Nc1cc(Nc2cc(-c3cccc(NC(=O)c4cc5c(s4)CCCC5)c3C)cn(C)c2=O)ccc1C(=O)N1CCOCC1
InChIKey: UQDKCJOIUBVSRC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of full length recombinant human N-terminal His tagged BKT expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr)4:1 as substrate pretreated for 60 mins followed by substrate addition after 1 hr by ADP-Glo luminescence assay
Measurement: IC50 = 16.5 nM (pChEMBL 7.78000020980835)
Descriptors: MW 651.79, ALogP 5.89, HBA 8, HBD 3, PSA 121.77, QED 0.2
Compound (SMILES): C[C@H](NC(=O)c1cc(Cl)cnc1Oc1ccc(F)cc1)c1ccc(C(=O)O)cc1
InChIKey: KQRDIJJCEPLGDK-LBPRGKRZSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Antagonist activity at human EP3 receptor
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 414.82, ALogP 4.86, HBA 4, HBD 2, PSA 88.52, QED 0.6
Compound (SMILES): CN1[C@@H]2CC[C@H]1c1c(sc(NC(=O)Nc3ccc(Cl)cc3)c1C(N)=O)C2.Cl
InChIKey: VFXQFPNKKZLQHQ-LYCTWNKOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 46000 nM (pChEMBL 4.340000152587891)
Descriptors: MW 390.9, ALogP 3.84, HBA 4, HBD 3, PSA 87.46, QED 0.74
Compound (SMILES): NC/C=C\CN(C[C@H]1Cc2ccccc2CN1)[C@H]1CCCc2cccnc21
InChIKey: VUXQRANDPGSPRS-QOZQEUDZSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant human CYP2D6 expressed in insect microsomes using AMMC as substrate preincubated for 30 mins followed by NADPH addition measured after 45 mins by fluorescence assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 362.52, ALogP 2.99, HBA 4, HBD 2, PSA 54.18, QED 0.78
Compound (SMILES): O=C(c1ccccc1)N1C[C@H]2OC34CCC1C2C31CCN(CCc2ccccc2)C4Cc2ccc(O)cc21
InChIKey: NTCCUWROZNYZLA-OUQYSMQKSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human delta opioid receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: EC50 = 0.61 nM (pChEMBL 9.210000038146973)
Descriptors: MW 506.65, ALogP 4.58, HBA 4, HBD 1, PSA 53.01, QED 0.56
Compound (SMILES): Cc1ncn(-c2ccc(C(=O)N[C@H]3[C@H]4CC[C@H]3N(c3ncc(Cl)c5cnoc35)C4)c(Cl)c2)n1
InChIKey: PQCRELQHENQSGP-RQUSPXKASA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in liver microsomes (unknown origin) assessed as formation of acetaminophen from phenacetin in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 484.35, ALogP 3.82, HBA 8, HBD 1, PSA 101.97, QED 0.47
Compound (SMILES): CC(C(=O)NCCOc1ccc2oc(=O)ccc2c1)c1ccc(-c2ccccc2)c(F)c1
InChIKey: RDCNYQNKGWIHTR-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 catalytic domain preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 23.5 nM (pChEMBL 7.630000114440918)
Descriptors: MW 431.46, ALogP 4.9, HBA 4, HBD 1, PSA 68.54, QED 0.33
Compound (SMILES): COc1ccccc1N1CCN(CCCC(=O)Nc2ccn3ncc(/C=N\O)c3c2)CC1
InChIKey: IBCJUIIXFRJMOE-UQQQWYQISA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]spiperone from human Dopamine D4 receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 436.52, ALogP 2.69, HBA 8, HBD 2, PSA 94.7, QED 0.32
Compound (SMILES): CN(CCCCOc1ccc2c(c1)NC(=O)CC2)[C@@H]1Cc2cccc3[nH]c(=O)n(c23)C1
InChIKey: WIJUWJDUUDINBR-GOSISDBHSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at renilla luciferase-tagged human dopamine D2 receptor expressed in HEK293 cells coexpressing mVenus-fused beta-arrestin 2 assessed as induction of beta-arrestin 2 recruitment by BRET assay
Measurement: EC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 420.51, ALogP 2.93, HBA 5, HBD 2, PSA 79.36, QED 0.58
Compound (SMILES): COc1n[nH]c2ncc(C#Cc3c(F)ccc(NS(=O)(=O)c4cccc(Cl)c4)c3F)cc12
InChIKey: NEDXWYOBFJNWEA-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 20 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYL2
Assay: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay
Measurement: IC50 = 14.7 nM (pChEMBL 7.829999923706055)
Descriptors: MW 474.88, ALogP 4.1, HBA 5, HBD 2, PSA 96.97, QED 0.43
Compound (SMILES): NC1(Cc2nc(-c3ccc(OC(F)(F)F)cc3)c[nH]2)COC1
InChIKey: QMSYRAZMYGWQJB-UHFFFAOYSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of 50% inactivated recombinant human Nav1.6 expressed in HEK293 cells at holding potential of -120 mV by manual patch electrophysiology method
Measurement: IC50 = 46000 nM (pChEMBL 4.340000152587891)
Descriptors: MW 313.28, ALogP 2.25, HBA 4, HBD 2, PSA 73.16, QED 0.91
Compound (SMILES): CC1CN(c2cncnc2)Cc2cc(C(=O)Nc3cc(CCN4CCN(C)CC4)cc(C(F)(F)F)c3)ccc21
InChIKey: OPEMWSXQLXWPSB-UHFFFAOYSA-N
Target: Epithelial discoidin domain-containing receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q08345
Assay: Lantha Screen Eu Kinase Activity Assay: The effects of compounds on the kinases DDR1 and DDR2 were assessed by using a Lantha Screen Eu kinase activity assay technology (Invitrogen, USA). Kinase reactions are performed in a 10 uL volume in low-volume 384-well plates. The kinases in reaction buffer consist of 50 mM HEPES pH 7.5, 0.01% BRU-35, 10 mM MgCl2, and 1 mM EGTA, the concentration of Fluorescein-Poly GAT substrate (Invitrogen, USA) in the assay is 100 nM. Kinase reactions were initiated with the addition of 100 nM ATP in the presence of serials of dilutions of compounds. The reactions were allowed to proceed for 1 h at room temperature before a 10 uL preparation of EDTA (20 mM) and Eu-labeled antibody (4 nM) in TR-FRET dilution buffer are added. The final concentration of antibody in the assay well is 2 nM, and the final concentration of EDTA is 10 mM. The plate is allowed to incubate at room temperature for one more hour before the TR-FRET emission ratios of 665 nm/340 nm were acquired on a PerkinElmer EnVision multilabel reader (Perkin-Elmer, Inc.). Data analysis and curve fitting were performed using GraphPad Prism4 software, resulting in the half maximal inhibitory concentration (IC50) shown in table 1. The functional assays of compounds on the kinase activities of c-kit and Abl were determined using the FRET-based Z'-Lyte assay system according to the manufacturer's instructions (Invitrogen, USA). Tyrosine 2 peptide was used as Abl substrate, and Ser/Thr 6 peptide was used as the substrate for c-kit. The reactions were carried out in 384-well plates in a 10 uL of reaction volume with appropriate amount of kinases in 50 mM HEPES (pH 7.5), 10 Mm MgCl2, 1 mM EGTA, and 0.01% Brij-35. The reactions were incubated 1 h at room temperature in the presence of 2 uM of substrate with 10 uM of ATP (for Abl1 assays) or 300 uM of ATP (kit assay) and in the presence of various concentrations of the compounds.
Measurement: IC50 = 36.7 nM (pChEMBL 7.429999828338623)
Descriptors: MW 538.62, ALogP 4.66, HBA 6, HBD 1, PSA 64.6, QED 0.49
Compound (SMILES): O=S(=O)(NCCCCN1CC=C(c2c[nH]c3ccc(Cl)cc23)CC1)c1cccc2ccccc12
InChIKey: KOMBSQZUWFYWJG-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylspiperone from human D2 receptor expressed in CHO-K1 cells after 60 mins by scintillation counting
Measurement: Ki = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 494.06, ALogP 5.82, HBA 3, HBD 2, PSA 65.2, QED 0.3
Compound (SMILES): O=C(C(=S)N1CCOCC1)c1ccc(Cl)cc1
InChIKey: IWEPJEXBCDPDQS-UHFFFAOYSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of PHGDH in human HL60 cells assessed as reduction in cell viability in serine depleted medium after 5 days by presto blue assay
Measurement: IC50 = 15500 nM (pChEMBL 4.809999942779541)
Descriptors: MW 269.75, ALogP 2.18, HBA 3, HBD 0, PSA 29.54, QED 0.61
Compound (SMILES): O=C1c2cc(-c3ccnc(NC4CCOCC4)n3)[nH]c2CCN1[C@H](CO)c1ccc(F)c(Cl)c1
InChIKey: UAIBOHCHIXSQEP-JOCHJYFZSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP
Measurement: IC50 < 0.31 nM (pChEMBL 9.508999824523926)
Descriptors: MW 485.95, ALogP 3.59, HBA 6, HBD 3, PSA 103.37, QED 0.49
Compound (SMILES): CC(C)Oc1cccnc1N(C)C1CCN(Cc2ccc(I)cc2)CC1
InChIKey: ZJAXDNQQFMPNAV-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Inhibition of sigma1 receptor (unknown origin)
Measurement: Ki = 82.1 nM (pChEMBL 7.090000152587891)
Descriptors: MW 465.38, ALogP 4.57, HBA 4, HBD 0, PSA 28.6, QED 0.58
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(F)cc3)CC2)nc2ccsc12
InChIKey: XEONIRSOONODDE-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 3B reverse transcriptase E138K mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 34.9 nM (pChEMBL 7.460000038146973)
Descriptors: MW 513.64, ALogP 6.85, HBA 7, HBD 1, PSA 74.07, QED 0.27
Compound (SMILES): Nc1ccc(-c2cnc3[nH]cc(-c4ccc(O)cc4)c3c2)cc1
InChIKey: ATXGVVQAUKKFAN-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of DYRK1A (unknown origin) using woodtide as substrate after 10 mins in presence of [gamma-33P]ATP by microbeta scintillation counting
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 301.35, ALogP 4.18, HBA 3, HBD 3, PSA 74.93, QED 0.49
Compound (SMILES): O=C(C1CCN(c2cc(Oc3ccc(F)cc3F)ncn2)CC1)N1Cc2ccccc2C1
InChIKey: AVVMQHQEYKLYQE-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Antagonist activity at recombinant human M3 receptor expressed in CHO cells co-expressing Gqi5 by calcium mobilization assay
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 436.46, ALogP 4.31, HBA 5, HBD 0, PSA 58.56, QED 0.61
Compound (SMILES): Cc1csc2cc([C@H](C)Nc3ncnc(N)c3C#N)c(Cc3cccc(CN4CCC4)c3)c(=O)n12
InChIKey: ITLXLQIYXORZBH-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human JeKo1 cells assessed as reduction in Akt phosphorylation at Ser473 residue preincubated for 60 mins followed by Anti-IgM stimulation for 10 mins by TR-FRET assay
Measurement: IC50 = 2.512 nM (pChEMBL 8.600000381469727)
Descriptors: MW 485.62, ALogP 3.88, HBA 9, HBD 2, PSA 112.34, QED 0.41
Compound (SMILES): C[C@H]1CCCCN1c1ccc(N2CCN(S(=O)(=O)c3ccccc3Cl)CC2)nn1
InChIKey: CEYPNEJNCVBNLW-INIZCTEOSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Antagonist activity at human recombinant muscarinic M3 receptor expressed in CHO cells co-transfected with Gqi5 in presence of EC80 acetylcholine by calcium mobilization assay
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 435.98, ALogP 3.02, HBA 6, HBD 0, PSA 69.64, QED 0.73
Compound (SMILES): CC1(C)[C@H](Nc2c(C(N)=O)cnn3cc(-c4ccc(C#N)nc4)cc23)CC[C@]1(C)N
InChIKey: XVDQGBYBUPDCBE-GCJKJVERSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human whole blood assessed as reduction in IL-2 induced IFN-gamma production after 18 hrs by ELISA
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 403.49, ALogP 2.68, HBA 7, HBD 3, PSA 135.12, QED 0.61
Compound (SMILES): Nc1ccc(-c2cccc(C(=O)NCCCCCCNc3ncnc4c3ncn4[C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2)s1
InChIKey: XPWJOKLEKNEYIH-TXAJWUPVSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Agonist activity at human A3AR expressed in FlpIn-CHO cells assessed as inhibition of forskolin-stimulated cAMP accumulation preincubated for 10 mins followed by forskolin addition measured after 30 mins by Alphascreen assay
Measurement: EC50 = 64.57 nM (pChEMBL 7.190000057220459)
Descriptors: MW 567.67, ALogP 2.15, HBA 12, HBD 6, PSA 180.67, QED 0.14
Compound (SMILES): Cc1cc(Oc2cncc(Cl)c2)cc(C(=O)Nc2ccc(F)cn2)n1
InChIKey: CEIBXTSWBBWOPN-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 5 mins followed by NADPH addition measured after 8 mins by LC/MS/MS analysis
Measurement: IC50 = 21500 nM (pChEMBL 4.670000076293945)
Descriptors: MW 358.76, ALogP 4.02, HBA 5, HBD 1, PSA 77, QED 0.76
Compound (SMILES): N#C[C@H]1CCOC[C@@H]1n1cc(C(N)=O)c(Nc2ccc(-n3ccnn3)cc2)n1
InChIKey: IEDBCDPKOHPADD-WBMJQRKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 in IL6-stimulated human ME180 cells expressing stably integrated beta-lactamase reporter gene under control of sis-inducible element by fluorescence assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 378.4, ALogP 1.41, HBA 9, HBD 2, PSA 136.67, QED 0.68
Compound (SMILES): CC(C)(C)SC[C@H]1N=C(c2ccccc2)c2ccccc2N(CCCCC(=O)O)C1=O
InChIKey: YJAVRZQWCDGEEO-HXUWFJFHSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Schistosoma mansoni
UniProt: A5H660
Assay: Inhibition of Schistosoma mansoni KDAC8 using (FAM)-labeled peptide as substrate after 60 mins by microfluidic assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 438.59, ALogP 5.03, HBA 4, HBD 1, PSA 69.97, QED 0.59
Compound (SMILES): CCC(=O)Nc1ccc2c(c1)[C@@]13CCN4CC5=CCO[C@H]6CC(=O)N2[C@H]1[C@H]6[C@H]5C[C@H]43
InChIKey: BNLMIPXTXOQLRY-VKEHPUIKSA-N
Target: Glycine receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23415
Assay: Antagonist activity at recombinant human glycine receptor alpha 1 expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50 mV holding potential by whole cell patch-clamp method
Measurement: IC50 = 201 nM (pChEMBL 6.699999809265137)
Descriptors: MW 405.5, ALogP 2.44, HBA 4, HBD 1, PSA 61.88, QED 0.77
Compound (SMILES): CC(C)(C)c1nc(N2CCN(CCCCNC(=O)c3cc4ccccc4s3)CC2)cc(C(F)(F)F)n1
InChIKey: XTFNKHQCBITNPG-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]spiperone from human D3 receptor expressed in CHO cell membranes
Measurement: Ki = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 519.64, ALogP 5.34, HBA 6, HBD 1, PSA 61.36, QED 0.43
Compound (SMILES): O=S(=O)(c1cncc2ccccc12)N1CCC(CCN2CCN(c3cccc(Cl)c3)CC2)CC1
InChIKey: VECUWLITDSFQFD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5-HT7 receptor expressed in HEK293 cell membranes after 1 hr by microbeta liquid scintillation counting analysis
Measurement: Ki = 18 nM (pChEMBL 7.75)
Descriptors: MW 499.08, ALogP 4.5, HBA 5, HBD 0, PSA 56.75, QED 0.5
Compound (SMILES): CC1CN(c2cncnc2)Cc2cc(C(=O)Nc3cc(CN4CCN(C5CCCCC5)CC4)cc(C(F)(F)F)c3)ccc21
InChIKey: NFZXBQXIWXZUDR-UHFFFAOYSA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Lantha Screen Eu Kinase Activity Assay: The effects of compounds on the kinases DDR1 and DDR2 were assessed by using a Lantha Screen Eu kinase activity assay technology (Invitrogen, USA). Kinase reactions are performed in a 10 uL volume in low-volume 384-well plates. The kinases in reaction buffer consist of 50 mM HEPES pH 7.5, 0.01% BRU-35, 10 mM MgCl2, and 1 mM EGTA, the concentration of Fluorescein-Poly GAT substrate (Invitrogen, USA) in the assay is 100 nM. Kinase reactions were initiated with the addition of 100 nM ATP in the presence of serials of dilutions of compounds. The reactions were allowed to proceed for 1 h at room temperature before a 10 uL preparation of EDTA (20 mM) and Eu-labeled antibody (4 nM) in TR-FRET dilution buffer are added. The final concentration of antibody in the assay well is 2 nM, and the final concentration of EDTA is 10 mM. The plate is allowed to incubate at room temperature for one more hour before the TR-FRET emission ratios of 665 nm/340 nm were acquired on a PerkinElmer EnVision multilabel reader (Perkin-Elmer, Inc.). Data analysis and curve fitting were performed using GraphPad Prism4 software, resulting in the half maximal inhibitory concentration (IC50) shown in table 1. The functional assays of compounds on the kinase activities of c-kit and Abl were determined using the FRET-based Z'-Lyte assay system according to the manufacturer's instructions (Invitrogen, USA). Tyrosine 2 peptide was used as Abl substrate, and Ser/Thr 6 peptide was used as the substrate for c-kit. The reactions were carried out in 384-well plates in a 10 uL of reaction volume with appropriate amount of kinases in 50 mM HEPES (pH 7.5), 10 Mm MgCl2, 1 mM EGTA, and 0.01% Brij-35. The reactions were incubated 1 h at room temperature in the presence of 2 uM of substrate with 10 uM of ATP (for Abl1 assays) or 300 uM of ATP (kit assay) and in the presence of various concentrations of the compounds.
Measurement: IC50 = 945 nM (pChEMBL 6.03000020980835)
Descriptors: MW 592.71, ALogP 6.32, HBA 6, HBD 1, PSA 64.6, QED 0.36
Compound (SMILES): CCN(CCCCCCN1C(=O)c2ccccc2C1=O)Cc1ccccc1
InChIKey: NPQZWFHXMBANFC-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine chloride as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 364.49, ALogP 4.37, HBA 3, HBD 0, PSA 40.62, QED 0.46
Compound (SMILES): COc1ccccc1CN(C)CCCCN1C(=O)c2ccccc2C1=O
InChIKey: QXXKSCJHTHUCPD-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B expressed in baculovirus infected BTI insect cells using kynuramine as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 11600 nM (pChEMBL 4.940000057220459)
Descriptors: MW 352.43, ALogP 3.2, HBA 4, HBD 0, PSA 49.85, QED 0.54
Compound (SMILES): C[C@H]1CN(c2cncnc2)Cc2cc(C(=O)Nc3cc(CN4CCCN(C)CC4)cc(C(F)(F)F)c3)ccc21
InChIKey: DDPFCUXJEFSBMK-FQEVSTJZSA-N
Target: Epithelial discoidin domain-containing receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q08345
Assay: Binding affinity to human DNA-tagged DDR1 expressed in bacterial expression system measured after 1 hr by quantitative PCR analysis
Measurement: Kd = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 538.62, ALogP 5.01, HBA 6, HBD 1, PSA 64.6, QED 0.49
Compound (SMILES): CCOc1cc(C(=O)Nc2cc(C(F)(F)F)ccn2)ccc1-c1nc(C23CCC(C(=O)O)(CC2)CC3)n2ccnc(N)c12
InChIKey: LQQCSYOAQDXWAD-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 594.59, ALogP 5.72, HBA 8, HBD 3, PSA 144.73, QED 0.25
Compound (SMILES): CNC(=O)N1CCc2c(c(N3CCCc4cc(-c5cnn(C)c5)c(C(F)F)cc43)nn2C2CCOCC2)C1
InChIKey: CQCWHSDMJBAGDC-UHFFFAOYSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Inhibition of CBP in human PBMC derived naive CD4-positive T cells assessed as decrease in FOXP3 mRNA level in Treg cells measured after 4 days by quantitative reverse transcriptase-PCR method
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 525.6, ALogP 4.35, HBA 7, HBD 1, PSA 80.45, QED 0.55
Compound (SMILES): O=C1NC(=O)[C@](CNC(=O)c2cc3cc(C(F)(F)F)ccc3o2)(C2CC2)N1
InChIKey: INOYENJSYPDBEC-INIZCTEOSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of human MMP1 using Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH as substrate measured after 2 to 4 hrs by fluorescence analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 381.31, ALogP 2.17, HBA 4, HBD 3, PSA 100.44, QED 0.71
Compound (SMILES): O=C1c2cc(-c3ccnc(NC4CCOCC4)n3)[nH]c2CCN1Cc1ccccc1
InChIKey: KERNFUCXORNNFU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP
Measurement: IC50 < 0.32 nM (pChEMBL 9.494999885559082)
Descriptors: MW 403.49, ALogP 3.26, HBA 5, HBD 2, PSA 83.14, QED 0.68
Compound (SMILES): NC(=O)c1cccc(NC(=O)/C=C\C(=O)N2CCN(c3ccc(-c4ccccc4)cc3)CC2)c1
InChIKey: AOHKATYJFHGYRV-YPKPFQOOSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of recombinant human His6-tagged PARP5a catalytic domain (1091 to 1325 residues) expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay
Measurement: IC50 = 9800 nM (pChEMBL 5.010000228881836)
Descriptors: MW 454.53, ALogP 3.3, HBA 4, HBD 2, PSA 95.74, QED 0.56
Compound (SMILES): CCC(=O)NCC(CO)c1cccc2ccc(OC)cc12
InChIKey: HEPRAZQZDVDTHU-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Agonist activity at human MT2 receptor expressed in CHO cells after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 2.754 nM (pChEMBL 8.5600004196167)
Descriptors: MW 287.36, ALogP 2.45, HBA 3, HBD 2, PSA 58.56, QED 0.86
Compound (SMILES): c1ccc(-c2cccc3nc(-c4cncnc4)nc(NCc4ccccn4)c23)cc1
InChIKey: UVJHJIXYGIZLLF-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Caliper Kinase Assay: The analyses were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 μl of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 390.45, ALogP 4.76, HBA 6, HBD 1, PSA 76.48, QED 0.47
Compound (SMILES): FC(F)(F)c1cccc(/C=C/c2cnc3ccc(Cl)nn23)c1
InChIKey: SOIYEAXWSCNVLD-SNAWJCMRSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Mus musculus
UniProt: O35491
Assay: Inhibition of GST tagged recombinant mouse CLK2 expressed in Escherichia coli using RS peptide as substrate after 30 mins by [gamma-33P]ATP based scintillation counting analysis
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 323.7, ALogP 4.57, HBA 3, HBD 0, PSA 30.19, QED 0.69
Compound (SMILES): CCC(=O)NCc1cc(C(=O)NCCNC(=O)CCc2cn(CCCCC3CCN(CC(=O)N4c5ccccc5NC(=O)c5ccccc54)CC3)cn2)cc(C(=O)NCCNC(=O)CCc2cn(CCCCC3CCN(CC(=O)N4c5ccccc5NC(=O)c5ccccc54)CC3)cn2)c1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: VQYRIMDBHKNCQV-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Competitive antagonist activity at human muscarinic acetylcholine receptor M2 expressed in HEK293 cells coexpressing HA tagged Galpha-protein qi5 assessed as inhibition of 1 uM carbachol-induced IP1 accumulation preincubated for 30 mins followed by carbachol addition measured after 1 hr by HTRF assay
Measurement: IC50 = 173.78 nM (pChEMBL 6.760000228881836)
Descriptors: MW 1358.66
Compound (SMILES): CC(C)(C)c1ccccc1Oc1ccc(-c2cccc(C(=O)O)c2)cc1NC(=O)Nc1ccc(OC(F)(F)F)cc1
InChIKey: SLDGXRAZEJMRBM-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 564.56, ALogP 8.68, HBA 4, HBD 3, PSA 96.89, QED 0.21
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCC(NCc3cccc(C(F)(F)F)c3)CC2)nc2ccsc12
InChIKey: NJZLFGQABZGTLC-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 3B reverse transcriptase E138K mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 > 707 nM (pChEMBL 6.151000022888184)
Descriptors: MW 551.64, ALogP 7.5, HBA 7, HBD 2, PSA 82.86, QED 0.25
Compound (SMILES): COc1ccc2c(c1)CCN1CCCC21
InChIKey: OCEINGJGFNLPGA-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Antagonist activity at rat alpha3beta4 nAChR expressed in HEK293 cells assessed as inhibition of (S)-nicotine-induced current response measured up to 90 secs by FMP assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 203.28, ALogP 2.39, HBA 2, HBD 0, PSA 12.47, QED 0.69
Compound (SMILES): CCCN(CCCCOc1ccc2ccnn2c1)[C@H]1CCc2c(O)cccc2C1
InChIKey: JQXMVFBXXAKVDC-NRFANRHFSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]spiperone from human Dopamine D4 receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 393.53, ALogP 4.47, HBA 5, HBD 1, PSA 50, QED 0.55
Compound (SMILES): CC[C@@H](CO)Nc1ccc2ncc(-c3ccsc3)n2n1
InChIKey: OJYINLHOEHUFHI-NSHDSACASA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Mus musculus
UniProt: O35491
Assay: Inhibition of GST tagged recombinant mouse CLK2 expressed in Escherichia coli using RS peptide as substrate after 30 mins by [gamma-33P]ATP based scintillation counting analysis
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 288.38, ALogP 2.64, HBA 6, HBD 2, PSA 62.45, QED 0.76
Compound (SMILES): COc1cc2ncnc(Nc3n[nH]cc3C#N)c2cc1OC
InChIKey: OQUOJUDRDBAFJQ-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of recombinant human CDK2/cyclin A using histone H1 as substrate after 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 296.29, ALogP 1.99, HBA 7, HBD 2, PSA 108.74, QED 0.76
Compound (SMILES): CC#CCOc1ccc(C(=O)N[C@H](C(=O)NO)C(C)(C)N)cc1
InChIKey: JPCUWLVKAJJSLN-CYBMUJFWSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human HDAC8
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 319.36, ALogP 0.43, HBA 5, HBD 4, PSA 113.68, QED 0.34
Compound (SMILES): CCOC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(C#Cc4ccc(Br)s4)nc31)[C@H](O)[C@@H]2O
InChIKey: OWAPVYBGILLXPH-RUZZFIIFSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Enhancing of [3H]WIN35,428 binding to recombinant human DAT expressed in HEK293 cell membranes pre-incubated for 10 mins before radioligand addition and measured 90 mins after radioligand addition by micro beta scintillation counting analysis relative to control
Measurement: EC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 518.39, ALogP 1.94, HBA 10, HBD 3, PSA 122.39, QED 0.35
Compound (SMILES): Cl.Cl.NCc1cc(Oc2cccc(C(=O)N3CC[C@@H](N)C3)c2)nc(C(F)(F)F)c1
InChIKey: QOLRGZXXPUCRFH-FFXKMJQXSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction in amine oxidase activity incubated for 2 hrs by Amplex red based fluorescence assay
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 380.37, ALogP 2.52, HBA 5, HBD 2, PSA 94.47, QED 0.85
Compound (SMILES): CCn1nnc([C@H]2O[C@@H](n3cnc4c(NCc5cccc(F)c5)ncnc43)[C@H](O)[C@@H]2O)n1
InChIKey: PWGOJUSCXLZCQN-QCUYGVNKSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Agonist activity at recombinant human adenosine A2A receptor expressed in CHO cell membranes assessed as stimulation of adenylyl cyclase activity by [alpha-32P]ATP assay
Measurement: EC50 = 14.4 nM (pChEMBL 7.840000152587891)
Descriptors: MW 441.43, ALogP 0.58, HBA 12, HBD 3, PSA 148.92, QED 0.39
Compound (SMILES): CC1=C(CC(=O)NCCOc2ccc3oc(=O)ccc3c2)c2cc(F)ccc2/C1=C\c1ccc([S+](C)[O-])cc1
InChIKey: XOKLEXHVYHSJAW-YSMPRRRNSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 catalytic domain preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 30.8 nM (pChEMBL 7.510000228881836)
Descriptors: MW 543.62, ALogP 5.58, HBA 5, HBD 1, PSA 91.6, QED 0.18
Compound (SMILES): Cc1cnc(C(=O)N[C@H]2CCOC[C@@H]2O)cc1Cc1ccc(-c2cscn2)cc1
InChIKey: VVZZHFMLRHJXTO-RXVVDRJESA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Agonist activity at muscarinic M1 receptor (unknown origin) expressed in CHO cells assessed as accumulation of inositol phosphate measured after 30 mins by HTRF assay
Measurement: EC50 >= 9200 nM (pChEMBL 5.035999774932861)
Descriptors: MW 409.51, ALogP 2.98, HBA 6, HBD 2, PSA 84.34, QED 0.68
Compound (SMILES): CN[C@@H]1Cc2cccc3c2n(c(=O)n3CCCCCCCCOCCCCc2ccccc2)C1
InChIKey: QGNVJFHGWZQUHS-AREMUKBSSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at renilla luciferase-tagged human dopamine D2 receptor expressed in HEK293 cells coexpressing mVenus-fused beta-arrestin 2 assessed as induction of beta-arrestin 2 recruitment by BRET assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 463.67, ALogP 5.33, HBA 5, HBD 1, PSA 48.19, QED 0.31
Compound (SMILES): C=CC(=O)Nc1cc(Nc2n[nH]c3ccc(-c4ccc(F)cc4)cc23)c(OC)cc1N(C)CCN(C)C
InChIKey: IOFPXKOUVACVHI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR delE746_A750 mutant in human HCC827 cells assessed as reduction in cell viability after 96 hrs by CellTiterGlo assay
Measurement: EC50 = 459 nM (pChEMBL 6.340000152587891)
Descriptors: MW 502.59, ALogP 5.24, HBA 6, HBD 3, PSA 85.52, QED 0.26