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: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin) using L-alpha-phosphatidylinositol as substrate after 40 mins by ATP depletion assay
Measurement: IC50 = 208 nM (pChEMBL 6.679999828338623)
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: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of p38alpha MAPK (unknown origin) assessed as decrease in ATF2 phosphorylation at Thr69/71 at 1 uM after 1 hr by ELISA
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
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: Nicotinic acetylcholine receptor alpha-1/beta-1/delta/epsilon (PROTEIN COMPLEX), Homo sapiens
UniProt: Q04844
Assay: Agonist activity at alpha1beta1deltaepsilon 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: 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 192.28, ALogP 1.83, HBA 1, HBD 0, PSA 9.23, QED 0.62
Compound (SMILES): CN1C(=O)[C@@H](N2CCc3cn(CC4CCS(=O)(=O)CC4)nc3C2=O)COc2ccccc21
InChIKey: IVVSBEQDCAZLFY-SFHVURJKSA-N
Target: Tyrosine-protein kinase ABL2 (SINGLE PROTEIN), Homo sapiens
UniProt: P42684
Assay: Arg(ABL2LGF1) 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): 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 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O96013
Assay: Inhibition of human PAK4 assessed as enzymatic activity incubated for 20 mins by filter binding method
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 411.9, ALogP 3.06, HBA 6, HBD 3, PSA 98.83, QED 0.61
Compound (SMILES): Cc1cc(=O)oc2cc(OCc3ccc(Br)cc3)ccc12
InChIKey: FVWAAOMTWGZPCD-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at DHT-induced Androgen receptor in human LNCaP cells transfected with ARR2PB-eGFP incubated for 3 days
Measurement: IC50 = 870 nM (pChEMBL 6.059999942779541)
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), Rattus norvegicus
UniProt: P29476
Assay: Inhibition of recombinant rat nNOS expressed in Escherichia coli using L-arginine as substrate after 30 secs by hemoglobin capture assay
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
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: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Displacement of [125I]-NDP-MSH from human MC1R expressed in HEK293 cells
Measurement: IC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 3928.57
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCc3cc(O)c(O)cc3[C@@H]2c2ccccc2)cc1
InChIKey: UBKCMPKCMMEDIG-NRFANRHFSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human carbonic anhydrase 14 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 424.48, ALogP 2.53, HBA 5, HBD 3, PSA 120.93, QED 0.56
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)OCCO3)cc1NC(=O)c1ccc2c(c1)CCCN2
InChIKey: LLTXIVYBCVSFHB-UHFFFAOYSA-N
Target: Heat shock factor protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00613
Assay: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA
Measurement: IC50 = 223.87 nM (pChEMBL 6.650000095367432)
Descriptors: MW 443.5, ALogP 4.63, HBA 5, HBD 3, PSA 88.69, QED 0.55
Compound (SMILES): O=C(C1CCN(c2cc(Oc3ccccc3F)ncn2)CC1)N1CCc2ccccc2C1
InChIKey: OBLWLENBNRYSCO-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Antagonist activity at recombinant human M4 receptor expressed in CHO cells co-expressing Gqi5 by calcium mobilization assay
Measurement: IC50 = 123.03 nM (pChEMBL 6.909999847412109)
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: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp method
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 377.49, ALogP 3.42, HBA 5, HBD 3, PSA 98.44, QED 0.65
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 EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as inhibition of PGE2-induced cAMP level by HTS assay
Measurement: Kd = 2.455 nM (pChEMBL 8.609999656677246)
Descriptors: MW 414.82, ALogP 4.86, HBA 4, HBD 2, PSA 88.52, QED 0.6
Compound (SMILES): NC/C=C\CN(C[C@H]1Cc2ccccc2CN1)[C@H]1CCCc2cccnc21
InChIKey: VUXQRANDPGSPRS-QOZQEUDZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
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: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa 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 = 404 nM (pChEMBL 6.389999866485596)
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 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in liver microsomes (unknown origin) assessed as formation of 4-hydroxydiclofenac from diclofenac 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 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA12 preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 5.9 nM (pChEMBL 8.229999542236328)
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: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from human 5-HT2A receptor expressed in HEK293T cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
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 human dopamine D2 receptor expressed in HEK293 cells coexpressing renilla luciferase-fused Galphai1/GFP10-fused Ggamma2 by BRET assay
Measurement: EC50 = 188.8 nM (pChEMBL 6.71999979019165)
Descriptors: MW 420.51, ALogP 2.93, HBA 5, HBD 2, PSA 79.36, QED 0.58
Compound (SMILES): NC1(Cc2nc(-c3ccc(OC(F)(F)F)cc3)c[nH]2)COC1
InChIKey: QMSYRAZMYGWQJB-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of 50% inactivated recombinant human Nav1.7 expressed in HEK293 cells at holding potential of -120 mV by PatchXpress automated electrophysiology method
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
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: 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 = 449 nM (pChEMBL 6.349999904632568)
Descriptors: MW 538.62, ALogP 4.66, HBA 6, HBD 1, PSA 64.6, QED 0.49
Compound (SMILES): CC(C)Oc1cccnc1N(C)C1CCN(Cc2ccc(I)cc2)CC1
InChIKey: ZJAXDNQQFMPNAV-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Inhibition of human dopamine D4 receptor
Measurement: Ki = 0.33 nM (pChEMBL 9.479999542236328)
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 F227L/V106A double mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 103 nM (pChEMBL 6.989999771118164)
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 protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of human 130-end recombinant CLK1 assessed as remaining activity using ERMRPRKRQGSVR as substrate by [gamma-32P]ATP binding based scintillation counting based analysis
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
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 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 = 1130 nM (pChEMBL 5.949999809265137)
Descriptors: MW 436.46, ALogP 4.31, HBA 5, HBD 0, PSA 58.56, QED 0.61
Compound (SMILES): C[C@H]1CCCCN1c1ccc(N2CCN(S(=O)(=O)c3ccccc3Cl)CC2)nn1
InChIKey: CEYPNEJNCVBNLW-INIZCTEOSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Antagonist activity at human recombinant muscarinic M5 receptor expressed in CHO cells co-transfected with Gqi5 in presence of EC80 acetylcholine by calcium mobilization assay
Measurement: IC50 = 6500 nM (pChEMBL 5.190000057220459)
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: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by flux-based assay
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 403.49, ALogP 2.68, HBA 7, HBD 3, PSA 135.12, QED 0.61
Compound (SMILES): CCNC(=O)c1cc2c(N3CCOC[C@@H]3C)ccnc2[nH]1
InChIKey: RPMGXDCRCWWCRY-JTQLQIEISA-N
Target: Oxidized purine nucleoside triphosphate hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P36639
Assay: Inhibition of human full length MTH1 using 8-Oxo-2-dGTP as substrate preincubated for 15 mins followed substrate addition measured after 1 hr by PPilight pyrophosphate-detection based assay
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 288.35, ALogP 1.54, HBA 4, HBD 2, PSA 70.25, QED 0.9
Compound (SMILES): Cc1cc(Oc2cncc(Cl)c2)cc(C(=O)Nc2ccc(F)cn2)n1
InChIKey: CEIBXTSWBBWOPN-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using tacrine as substrate preincubated for 5 mins followed by NADPH addition measured after 8 mins by LC/MS/MS analysis
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
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 JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 in EPO-stimulated human TF1 cells expressing stably integrated beta-lactamase reporter gene under control of STAT5 response elements in interferon regulatory factor 1 gene promoter by fluorescence assay
Measurement: IC50 = 254 nM (pChEMBL 6.590000152587891)
Descriptors: MW 378.4, ALogP 1.41, HBA 9, HBD 2, PSA 136.67, QED 0.68
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 (alpha-1/beta) (PROTEIN COMPLEX), Homo sapiens
UniProt: P48167
Assay: Antagonist activity at recombinant human glycine receptor alpha 1 beta expressed in HEK293 cells assessed as inhibition of glycine-induced current at -50mV holding potential by whole cell patch-clamp method
Measurement: IC50 = 311 nM (pChEMBL 6.510000228881836)
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(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]spiperone from human D4 receptor expressed in CHO cell membranes
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 519.64, ALogP 5.34, HBA 6, HBD 1, PSA 61.36, QED 0.43
Compound (SMILES): CC1CN(c2cncnc2)Cc2cc(C(=O)Nc3cc(CN4CCN(C5CCCCC5)CC4)cc(C(F)(F)F)c3)ccc21
InChIKey: NFZXBQXIWXZUDR-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 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: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE using butyrylthiocholine chloride as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 15800 nM (pChEMBL 4.800000190734863)
Descriptors: MW 364.49, ALogP 4.37, HBA 3, HBD 0, PSA 40.62, QED 0.46
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: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Btk Enzyme Activity Assay: BTK enzymatic activity was determined with the LANCE (Lanthanide Chelate Excite) TR-FRET (Time-resolved fluorescence resonance energy transfer) assay. In this assay, the potency (IC50) of each compound was determined from an eleven point (1:3 serial dilution; final compound concentration range in assay from 1 μM to 0.017 nM) titration curve using the following outlined procedure. To each well of a black non-binding surface Corning 384-well microplate (Corning Catalog #3820), 5 nL of compound (2000 fold dilution in final assay volume of 10 μL) was dispensed, followed by the addition of 7.5 μL of 1× kinase buffer (50 mM Hepes 7.5, 10 mM MgCl2, 0.01% Brij-35, 1 mM EGTA, 0.05% BSA & 1 mM DTT) containing 5.09 pg/μL (66.67 pM) of BTK enzyme (recombinant protein from baculovirus-transfected Sf9 cells: full-length BTK, 6HIS-tag cleaved). Following a 60 minute compound & enzyme incubation, each reaction was initiated by the addition of 2.5 μL 1× kinase buffer containing 8 μM biotinylated A5 peptide (Biotin-EQEDEPEGDYFEWLE-NH2) (SEQ.ID.NO.: 1), and 100 μM ATP. The final reaction in each well of 10 μL consists of 50 pM hBTK, 2 μM biotin-A5-peptide, and 25 μM ATP. Phosphorylation reactions were allowed to proceed for 120 minutes. Reactions were immediately quenched by the addition of 20 uL of 1× quench buffer (15 mM EDTA, 25 mM Hepes 7.3, and 0.1% Triton X-100) containing detection reagents (0.626 nM of LANCE-Eu-W1024-anti-phosphoTyrosine antibody, PerkinElmer and 86.8 nM of Streptavidin-conjugated Dylight 650, Dyomics/ThermoFisher Scientific). After 60 minutes incubation with detection reagents, reaction plates were read on a PerkinElmer EnVision plate reader using standard TR-FRET protocol. Briefly, excitation of donor molecules (Eu-chelate:anti-phospho-antibody) with a laser light source at 337 nm produces energy that can be transferred to Dylight-650 acceptor molecules if this donor:acceptor pair is within close proximity Fluorescence intensity at both 665 nm (acceptor) and 615 nm (donor) are measured and a TR-FRET ratio calculated for each well (acceptor intensity/donor intensity). IC50 values were determined by 4 parameter robust fit of TR-FRET ratio values vs. (Log10)) compound concentrations.
Measurement: IC50 = 0.34 nM (pChEMBL 9.470000267028809)
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: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of biotinylated histone H3K14 peptide ligand from recombinant His-tagged TAF1 bromodomain-2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
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: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of human MMP2 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 = 5800 nM (pChEMBL 5.239999771118164)
Descriptors: MW 381.31, ALogP 2.17, HBA 4, HBD 3, PSA 100.44, QED 0.71
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 = 9772.37 nM (pChEMBL 5.010000228881836)
Descriptors: MW 454.53, ALogP 3.3, HBA 4, HBD 2, PSA 95.74, QED 0.56
Compound (SMILES): c1ccc(-c2cccc3nc(-c4cncnc4)nc(NCc4ccccn4)c23)cc1
InChIKey: UVJHJIXYGIZLLF-UHFFFAOYSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
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 CLK3 (SINGLE PROTEIN), Mus musculus
UniProt: O35492
Assay: Inhibition of GST tagged recombinant mouse CLK3 expressed in Escherichia coli using RS peptide as substrate after 30 mins by [gamma-33P]ATP based scintillation counting analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
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 10 uM carbachol-induced IP1 accumulation preincubated for 30 mins followed by carbachol addition measured after 1 hr by HTRF assay
Measurement: IC50 = 263.03 nM (pChEMBL 6.579999923706055)
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 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate
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 F227L/V106A double 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 subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Antagonist activity at human alpha7 nAChR expressed in HEK293 cells co-expressing Ric-3/NACHO assessed as inhibition of ACh-induced calcium mobilization measured up to 90 secs in presence of PNU-120596 by FLIPR 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: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from human 5-HT2A receptor expressed in HEK293T cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 2000 nM (pChEMBL 5.699999809265137)
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 CLK3 (SINGLE PROTEIN), Mus musculus
UniProt: O35492
Assay: Inhibition of GST tagged recombinant mouse CLK3 expressed in Escherichia coli using RS peptide as substrate after 30 mins by [gamma-33P]ATP based scintillation counting analysis
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 288.38, ALogP 2.64, HBA 6, HBD 2, PSA 62.45, 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 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of human HDAC7
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): 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 A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Agonist activity at recombinant human adenosine A2B receptor expressed in CHO cell membranes assessed as stimulation of adenylyl cyclase activity by [alpha-32P]ATP assay
Measurement: EC50 = 1100 nM (pChEMBL 5.960000038146973)
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 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA12 preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 81.7 nM (pChEMBL 7.090000152587891)
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: Positive allosteric modulation of muscarinic M1 receptor (unknown origin) expressed in CHO cells assessed as increase in Ach-induced accumulation of inositol phosphate accumulation measured after 30 mins by HTRF assay
Measurement: EC50 = 447 nM (pChEMBL 6.349999904632568)
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: Antagonist activity at renilla luciferase-tagged human dopamine D2 receptor expressed in HEK293 cells coexpressing mVenus-fused beta-arrestin 2 assessed as reduction in quinpirole-mediated beta-arrestin 2 recruitment preincubated for 15 mins followed by quinpirole addition measured for 1 sec by BRET assay
Measurement: IC50 > 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 L858R/T790M double mutant in human NCI-H1975 cells assessed as reduction in cell viability after 96 hrs by CellTiterGlo assay
Measurement: EC50 = 694 nM (pChEMBL 6.159999847412109)
Descriptors: MW 502.59, ALogP 5.24, HBA 6, HBD 3, PSA 85.52, QED 0.26
Compound (SMILES): COc1ccc2c(c1)CC[N+](C)(C)C2.[I-]
InChIKey: YWASSVRYTISOMT-UHFFFAOYSA-M
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Agonist activity at human alpha7 nAChR expressed in HEK293 cells co-expressing Ric-3/NACHO assessed as induction of calcium mobilization measured up to 90 secs in presence of PNU-120596 by FLIPR assay
Measurement: EC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 192.28, ALogP 1.83, HBA 1, HBD 0, PSA 9.23, QED 0.62
Compound (SMILES): CN1C(=O)[C@@H](N2CCc3cn(CC4CCS(=O)(=O)CC4)nc3C2=O)COc2ccccc21
InChIKey: IVVSBEQDCAZLFY-SFHVURJKSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: ALK2(ACV1LGF1) 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): 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: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Displacement of Eu-NDP-MSH from human MC1R expressed in HEK293T cells after 2 hrs by DELFIA method
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 3928.57
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)OCCO3)cc1NC(=O)c1ccc2c(c1)CCCN2
InChIKey: LLTXIVYBCVSFHB-UHFFFAOYSA-N
Target: Heat shock factor protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00613
Assay: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 443.5, ALogP 4.63, HBA 5, HBD 3, PSA 88.69, QED 0.55
Compound (SMILES): CC1(C)[C@H](Nc2c(C(N)=O)cnn3cc(-c4ccccc4)cc23)CC[C@]1(C)N
InChIKey: DIFGSGNUHRNWPK-GCJKJVERSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 377.49, ALogP 3.42, HBA 5, HBD 3, PSA 98.44, QED 0.65
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 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in liver microsomes (unknown origin) assessed as formation of 4-hydroxymephenytoin from S-mephenytoin 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 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA II
Measurement: Ki > 10000 nM (pChEMBL 5)
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(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human Dopamine D2S receptor expressed in HEK293T cell membranes coexpressing GalphaoA incubated for 30 mins measured after 75 mins by [35S]GTPgammaS binding assay
Measurement: EC50 = 470 nM (pChEMBL 6.329999923706055)
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 human dopamine D2 receptor expressed in HEK293 cells coexpressing renilla luciferase-fused GalphaoA/GFP10-fused Ggamma2 by BRET assay
Measurement: EC50 = 157.8 nM (pChEMBL 6.800000190734863)
Descriptors: MW 420.51, ALogP 2.93, HBA 5, HBD 2, PSA 79.36, QED 0.58
Compound (SMILES): NC1(Cc2nc(-c3ccc(OC(F)(F)F)cc3)c[nH]2)COC1
InChIKey: QMSYRAZMYGWQJB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of recombinant human ERG expressed in HEK293 cells at holding potential of -120 mV by PatchXpress automated electrophysiology method
Measurement: IC50 = 10000 nM (pChEMBL 5)
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: 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 538.62, ALogP 4.66, HBA 6, HBD 1, PSA 64.6, QED 0.49
Compound (SMILES): CC(C)Oc1cccnc1N(C)C1CCN(Cc2ccc(I)cc2)CC1
InChIKey: ZJAXDNQQFMPNAV-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Inhibition of human dopamine D2 (long) receptor (unknown origin)
Measurement: Ki > 1000 nM (pChEMBL 6)
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 RES056 reverse transcriptase K103N/Y181C double mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 513.64, ALogP 6.85, HBA 7, HBD 1, PSA 74.07, QED 0.27
Compound (SMILES): O=C(C1CCN(c2cc(Oc3ccc(F)cc3F)ncn2)CC1)N1Cc2ccccc2C1
InChIKey: AVVMQHQEYKLYQE-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Antagonist activity at recombinant human M4 receptor expressed in CHO cells co-expressing Gqi5 by calcium mobilization assay
Measurement: IC50 = 323.59 nM (pChEMBL 6.489999771118164)
Descriptors: MW 436.46, ALogP 4.31, HBA 5, HBD 0, PSA 58.56, QED 0.61
Compound (SMILES): C[C@H]1CCCCN1c1ccc(N2CCN(S(=O)(=O)c3ccccc3Cl)CC2)nn1
InChIKey: CEYPNEJNCVBNLW-INIZCTEOSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08482
Assay: Antagonist activity at rat muscarinic M1 receptor by calcium mobilization assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 435.98, ALogP 3.02, HBA 6, HBD 0, PSA 69.64, QED 0.73
Compound (SMILES): CCNC(=O)c1cc2c(N3CCOC[C@@H]3C)ccnc2[nH]1
InChIKey: RPMGXDCRCWWCRY-JTQLQIEISA-N
Target: Oxidized purine nucleoside triphosphate hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P36639
Assay: Affinity On-target Cellular interaction (CETSA (cellular thermal shift assay in K562 cells)) EUB0000302b NUDT1
Measurement: EC50 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 288.35, ALogP 1.54, HBA 4, HBD 2, PSA 70.25, QED 0.9
Compound (SMILES): N#C[C@H]1CCOC[C@@H]1n1cc(C(N)=O)c(Nc2ccc(-n3ccnn3)cc2)n1
InChIKey: IEDBCDPKOHPADD-WBMJQRKESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [35S]-MK499 from human ERG expressed in HEK293 cell membranes
Measurement: IC50 = 13200 nM (pChEMBL 4.880000114440918)
Descriptors: MW 378.4, ALogP 1.41, HBA 9, HBD 2, PSA 136.67, QED 0.68
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: Displacement of [3H]strychnine from recombinant human glycine receptor alpha 1 expressed in HEK293 cell membranes after 30 mins by liquid scintillation counting method
Measurement: Ki = 67 nM (pChEMBL 7.170000076293945)
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: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from human 5-HT2A receptor expressed in HEK293T cell membranes
Measurement: Ki = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 519.64, ALogP 5.34, HBA 6, HBD 1, PSA 61.36, QED 0.43
Compound (SMILES): CCN(CCCCCCN1C(=O)c2ccccc2C1=O)Cc1ccccc1
InChIKey: NPQZWFHXMBANFC-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 = 12200 nM (pChEMBL 4.909999847412109)
Descriptors: MW 364.49, ALogP 4.37, HBA 3, HBD 0, PSA 40.62, QED 0.46
Compound (SMILES): CNC(=O)N1CCc2c(c(N3CCCc4cc(-c5cnn(C)c5)c(C(F)F)cc43)nn2C2CCOCC2)C1
InChIKey: CQCWHSDMJBAGDC-UHFFFAOYSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged TAF1 bromodomain-1 measured after 10 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
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: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition of human MMP3 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 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 381.31, ALogP 2.17, HBA 4, HBD 3, PSA 100.44, QED 0.71
Compound (SMILES): c1ccc(-c2cccc3nc(-c4cncnc4)nc(NCc4ccccn4)c23)cc1
InChIKey: UVJHJIXYGIZLLF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
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 CLK4 (SINGLE PROTEIN), Mus musculus
UniProt: O35493
Assay: Inhibition of GST tagged recombinant mouse CLK4 expressed in Escherichia coli using RS peptide as substrate after 30 mins by [gamma-33P]ATP based scintillation counting analysis
Measurement: IC50 = 320 nM (pChEMBL 6.5)
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: Displacement of [3H]UR-AP060 from human muscarinic acetylcholine receptor M2 expressed in CHOK9 cell homogenate after 3 hrs by liquid scintillation counting assay
Measurement: Ki = 1.047 nM (pChEMBL 8.979999542236328)
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 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BZR as substrate
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 RES056 reverse transcriptase K103N/Y181C double 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