lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#C[C@H]1C[C@@H]1C(=O)N[C@@]12C[C@@H]1CN(c1nc(Nc3cnn(CCO)c3)ncc1F)C2
InChIKey: OCNRQCROIYCWQL-NTHKCUKCSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human recombinant JAK1 assessed as level of phosphorylation in presence of peptide substrate 5FAM-KKSRGDYMTMQUID and ATP by mobility shift assay
Measurement: IC50 = 304 nM (pChEMBL 6.519999980926514)
Descriptors: MW 412.43, ALogP 0.4, HBA 9, HBD 3, PSA 131.99, QED 0.6
Compound (SMILES): Cc1nnc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(O[C@@H](C)C(F)(F)F)ccc(C(F)(F)F)n3n2)o1
InChIKey: PPZKUFDGGKRNJA-BTABJRDXSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 505.42, ALogP 4.1, HBA 9, HBD 1, PSA 93.61, QED 0.52
Compound (SMILES): O=C(Cc1ccc(F)cc1)Nc1ccc(-c2ccc3nc(Nc4ccc(C(=O)N5CCOCC5)cc4OCC(F)(F)F)nn3c2)cc1
InChIKey: AACZEBAKIQBZKP-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Mps-1 Kinase Assay: For the assay 50 nl of a 100-fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 μl of a solution of Mps-1 in assay buffer [0.1 mM sodium-ortho-vanadate, 10 mM MgCl2, 2 mM DTT, 25 mM Hepes pH 7.7, 0.05% BSA, 0.001% Pluronic F-127] were added and the mixture was incubated for 15 min at 22° C. to allow pre-binding of the test compounds to Mps-1 before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 μl of a solution of 16.7 adenosine-tri-phosphate (ATP, 16.7 μM=>final conc. in the 5 μl assay volume is 10 μM) and peptide substrate (1.67 μM=>final conc. in the 5 μl assay volume is 1 μM) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22° C. The concentration of Mps-1 in the assay was adjusted to the activity of the enzyme lot and was chosen appropriate to have the assay in the linear range, typical enzyme concentrations were in the range of about 1 nM (final conc. in the 5 μl assay volume). The reaction was stopped by the addition of 3 μl of a solution of HTRF detection reagents (100 mM Hepes pH 7.4, 0.1% BSA, 40 mM EDTA, 140 nM Streptavidin-XLent [#61GSTXLB, Fa. Cis Biointernational, Marcoule, France], 1.5 nM anti-phospho(Ser/Thr)-Europium-antibody [#AD0180, PerkinElmer LAS, Rodgau-Jügesheim, Germany].The resulting mixture was incubated 1 h at 22° C. to allow the binding of the phosphorylated peptide to the anti-phospho(Ser/Thr)-Europium-antibody. Subsequently the amount of phosphorylated substrate was evaluated by measurement of the resonance energy transfer from the Europium-labelled anti-phospho(Ser/Thr) antibody to the Streptavidin-XLent. Therefore, the fluorescence emissions at 620 nm and 665 nm after excitation at 350 nm was measured in a Viewlux TR-FRET reader (PerkinElmer LAS, Rodgau-Jügesheim, Germany). The “blank-corrected normalized ratio” (a Viewlux specific readout, similar to the traditional ratio of the emissions at 665 nm and at 622 nm, in which blank and Eu-donor crosstalk are subtracted from the 665 nm signal before the ratio is calculated) was taken as the measure for the amount of phosphorylated substrate. The data were normalised (enzyme reaction without inhibitor=0% inhibition, all other assay components but no enzyme=100% inhibition).
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 648.62, ALogP 5.87, HBA 8, HBD 2, PSA 110.09, QED 0.19
Compound (SMILES): CCOC(=O)c1ccc2[nH]c(-c3ccncc3)nc2c1
InChIKey: QNQJZNBSQQSQNP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase N2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16513
Assay: Displacement of tracer from PKN2 (unknown origin) by TR-FRET assay
Measurement: Ki = 21050 nM (pChEMBL 4.679999828338623)
Descriptors: MW 267.29, ALogP 2.8, HBA 4, HBD 1, PSA 67.87, QED 0.74
Compound (SMILES): Cc1ccc(CN2CCCN(C(=O)c3ccco3)CC2)c(C)c1
InChIKey: CXCKAMIEHBJAGY-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-Di-o-tolylguanidine from sigma-2 receptor in rat liver membranes after 120 mins by scintillation counting method
Measurement: Ki = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 312.41, ALogP 3.24, HBA 3, HBD 0, PSA 36.69, QED 0.87
Compound (SMILES): C[N+](C)(C)C[C@@H]1CO[C@@H](C(c2ccccc2)c2ccccc2)CO1.[I-]
InChIKey: LEEPHERKICQCQR-GZJHNZOKSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 870.96 nM (pChEMBL 6.059999942779541)
Descriptors: MW 326.46, ALogP 3.31, HBA 2, HBD 0, PSA 18.46, QED 0.79
Compound (SMILES): FC(F)(F)COc1cccn2nc(N[C@@H]3[C@@H]4CC[C@H]3CN(c3ccnc(C(F)(F)F)c3)C4)nc12
InChIKey: VHCFIFNXNHPLHF-FVCICTRLSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Binding affinity to PIK4CB (unknown origin)
Measurement: Kd = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 486.42, ALogP 4.41, HBA 7, HBD 1, PSA 67.58, QED 0.54
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@H]2[C@@H]3COC[C@@H]32)cc2c1O[C@@H](CF)[C@@H]2c1ccccc1
InChIKey: WZQLVEPIBAOOGF-PXTPFGJHSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: BET mutant TR-FRET assay (BRD4 BD2)
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 410.45, ALogP 2.28, HBA 4, HBD 2, PSA 76.66, QED 0.79
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](NC(=O)[C@H]4CC4(F)F)CC3)c12
InChIKey: OWAGRTBSGRSEOG-CKYFFXLPSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 350.37, ALogP 2.36, HBA 3, HBD 3, PSA 90.64, QED 0.79
Compound (SMILES): Cc1cc(Cl)cc(-c2ccnc3cc(CN4C(=O)CCC4=O)sc23)c1CN1CCNCC1
InChIKey: MJVNKLYUWIPXLC-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of USP7 in human RKO cells transfected with p53 luciferase reporter vector assessed as increase in p53-dependent luciferase activity measured after 18 hrs by BrightGlo luciferase assay
Measurement: EC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 469.01, ALogP 3.98, HBA 6, HBD 1, PSA 65.54, QED 0.57
Compound (SMILES): Cc1cc(C)cc(C2CCCN2Cc2ccc(Oc3ccc4c(=O)[nH]oc4c3)cc2)c1
InChIKey: BRAMTCAKURNZGZ-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from human kappa opiod receptor expressed in CHO cells incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 1411 nM (pChEMBL 5.849999904632568)
Descriptors: MW 414.51, ALogP 5.87, HBA 4, HBD 1, PSA 58.47, QED 0.44
Compound (SMILES): C=CC[C@H]1C(=O)C(C#N)=C[C@@]2(C)c3nc(-c4ccnc(C5CC5)c4)nc(-c4ccccc4F)c3CC[C@H]12
InChIKey: RFGPRCBQFFHPNI-TXVKUACNSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 490.58, ALogP 6.27, HBA 5, HBD 0, PSA 79.53, QED 0.39
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)CC1CC2(C1)CN(C)C2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: ICECJYVQJUQARO-SANMLTNESA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 531.7, ALogP 5.45, HBA 6, HBD 2, PSA 100.21, QED 0.28
Compound (SMILES): C[C@H](O)CN1CCN(CCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: MQDDJWTVOBHYHX-KRWDZBQOSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]citalopram from SERT in Sprague-Dawley rat midbrain membranes incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 3940 nM (pChEMBL 5.409999847412109)
Descriptors: MW 406.54, ALogP 3.79, HBA 4, HBD 1, PSA 26.71, QED 0.72
Compound (SMILES): CCNS(=O)(=O)c1ccccc1Nc1ncnc(Nc2ccc(N3CCN(C)CC3)c(OCCOCCOC)c2)n1
InChIKey: SPQDHCNLYOMXOD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of N-terminal GST-tagged human VEGFR2 cytoplasmic domain (790-1356 end amino acid residue) expressed in baculovirus expression system preincubated for 30 to 120 mins followed by incubation with substrate and ATP for 30 mins by off-chip mobility shift assay
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 586.72, ALogP 2.45, HBA 12, HBD 3, PSA 143.07, QED 0.23
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(CN3Cc4cn[nH]c4C3)c(Cl)c2)cc1C#Cc1cnc2cccnn12
InChIKey: AIKGYQDFIJRQIY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG incubated for 4 hrs by competitive fluorescence tracer binding based assay
Measurement: IC50 = 12100 nM (pChEMBL 4.920000076293945)
Descriptors: MW 507.99, ALogP 4.58, HBA 6, HBD 2, PSA 91.21, QED 0.35
Compound (SMILES): CCCCCCCCCCCCCC(=S)NCCCCC(NC(=O)OCc1ccccc1)C(=O)Nc1ccccc1
InChIKey: CJQGLLUJIVNREL-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of sirtuin 2 (unknown origin)
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 581.87, ALogP 8.71, HBA 4, HBD 3, PSA 79.46, QED 0.1
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CC2)cn(Cc2ccc(C)cc2)c1=O
InChIKey: ZDMIQTYADVSQGR-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 339.4, ALogP 1.46, HBA 4, HBD 2, PSA 80.2, QED 0.87
Compound (SMILES): C[C@H]1C(=O)C(C#N)=C[C@@]2(c3ccccc3)c3nc(-c4ccnc(C5CC5)c4)nc(-c4ccccc4F)c3CC[C@H]12
InChIKey: HFMPPZFFHRGCAS-RLABKUHLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 526.62, ALogP 6.74, HBA 5, HBD 0, PSA 79.53, QED 0.29
Compound (SMILES): C=CC(=O)NCCOc1cccc2[nH]c(-c3n[nH]c4ccccc34)cc12
InChIKey: HNQYJXVOTFUHRG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Binding affinity to ITK (unknown origin) using TK as substrate by HTRF assay
Measurement: Ki = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 346.39, ALogP 3.39, HBA 3, HBD 3, PSA 82.8, QED 0.37
Compound (SMILES): Cc1cc(Cl)cc(-c2ccnc3cc(CN4C(=O)C5C(C4=O)C5(C)C)sc23)c1NC1CCCNC1
InChIKey: UEAPPVUIFDAOQU-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of USP7 in human RKO cells transfected with p53 luciferase reporter vector assessed as increase in p53-dependent luciferase activity measured after 18 hrs by BrightGlo luciferase assay
Measurement: EC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 509.08, ALogP 5.23, HBA 6, HBD 2, PSA 74.33, QED 0.46
Compound (SMILES): O=C(O)c1ccc(CO[N+](=O)[O-])cc1
InChIKey: NXYIECYJINSHGC-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-di-o-tolylguanidine from sigma2 receptor (unknown origin) incubated for 1 hr in presence of (+)SKF10047 by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 197.15, ALogP 1.09, HBA 4, HBD 1, PSA 89.67, QED 0.58
Compound (SMILES): C[N+](C)(C)C[C@@H]1CO[C@@H](c2ccccc2)[C@@H](c2ccccc2)O1.[I-]
InChIKey: HERDQXDYIAMKFW-QGPGBOAMSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 239.88 nM (pChEMBL 6.619999885559082)
Descriptors: MW 312.43, ALogP 3.59, HBA 2, HBD 0, PSA 18.46, QED 0.8
Compound (SMILES): NC(=O)Nc1ccccc1-c1cnc2c(c1)C[C@@]1(OCCCc3ccccc3)[C@H]3Cc4ccc(O)c5c4[C@@]1(CCN3CC1CC1)[C@H]2O5
InChIKey: BVUHEFGUIAPQIC-WIQMZKQSSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki > 3333 nM (pChEMBL 5.4770002365112305)
Descriptors: MW 628.77, ALogP 6.3, HBA 6, HBD 3, PSA 109.94, QED 0.19
Compound (SMILES): CC(C)Oc1cc(N2[C@H](C)COC[C@@H]2C)nc2c(-c3ccn[nH]3)nccc12
InChIKey: XXIDXEBDJANSDE-OKILXGFUSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Time-Resolved Fluorescence Energy Transfer (TR-FRET Tracer B): To determine of binding activity of the test compounds, full-length human ATR protein was expressed and purified together with ATRIP as described above. Furthermore, a fluorescently labelled compound (tracer B) was used as a tracer molecule. Detection of the binding event of the tracer was achieved by time-resolved fluorescence energy transfer (TR-FRET). We used an anti-GST-Terbium antibody (CisBio) that binds to the GST-tag at the N-terminus of ATR-kinase. Excitation of Terbium with 337 nm light results in emission of fluorescent light with 545 nm. In case a tetrameric complex has formed (antiGST-Tb+GST-ATR+Strp2-ATRIP+tracer), part of the energy will be transferred from the Terbium to the fluorophore that itself emits light of 570 nm. Displacement of the fluorescent tracer by a test compound leads to a reduction of the TR-FRET-signal.For the assay 50 nl of a 100-fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (MTP, Greiner Bio-One, Frickenhausen, Germany). To prepare the ATR-working solution, ATR/ATRIP stock solution was diluted in assay buffer [50 mM HEPES (pH 7.0), 10 mM MgCl2, 1 mM DTT, 0.01% (w/v) Igepal, 0.01% (w/v) BSA] to 4.2 nM protein concentration (concentration may vary from lot to lot of protein preparation). AntiGST-Tb antibody was diluted to 4.2 nM. The ATR-working solution was incubated for 30 min at 22° C. prior to dispensing to pre-form the complex of antiGST-Tb+GST-ATR+ATRIP. Then, 3 μl of the ATR-working solution were added to the test compound and the mixture was incubated for 10 min at 22° C. to allow pre-binding of the test compounds to ATR/ATRIP. Then, 2 μl of a 100 nM solution of either tracer A or B in assay buffer were added to the ATR-working solution. The resulting mixture was incubated for 30 min at 22° C. The measurement of the TR-FRET signal was performed in a standard HTRF-compatible MTP reader instrument (e.g. BMG Pherastar) by recording the fluorescence emissions at 545 nm and 570 nm after excitation at 337-350 nm. The ratio between emission at 570 nm divided by emission at 545 nm was calculated to give the well ratio. The experimental data (well ratios) were normalised by the following way: positive control contained ATR-working solution plus either tracer A or B solution (=0% inhibition), the negative control contained all components except GST-ATR/ATRIP (=100% inhibition).
Measurement: IC50 = 615 nM (pChEMBL 6.210000038146973)
Descriptors: MW 367.45, ALogP 3.42, HBA 6, HBD 1, PSA 76.16, QED 0.76
Compound (SMILES): O=c1sn(-c2cccc3c2CCCC3)c(=O)n1Cc1ccccc1
InChIKey: RRUPHLBEMFHTJY-UHFFFAOYSA-N
Target: Sortase A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q9S446
Assay: Inhibition of Staphylococcus aureus SrtA delta N24 mutant expressed in Escherichia coli BL21 (DE3) assessed as reduction in IsdA (64 to 323 residues) transpeptidation incubated for 20 mins by SDS-PAGE analysis
Measurement: IC50 = 31900 nM (pChEMBL 4.5)
Descriptors: MW 338.43, ALogP 2.99, HBA 5, HBD 0, PSA 44, QED 0.74
Compound (SMILES): COc1nc(-c2ccncc2)nc2c1CC[C@@H]1[C@@H](C)C(=O)C(C#N)=C[C@@]21C
InChIKey: OEIFLGGCKNMJLG-YDZGXFTCSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 461 nM (pChEMBL 6.340000152587891)
Descriptors: MW 360.42, ALogP 3.04, HBA 6, HBD 0, PSA 88.76, QED 0.82
Compound (SMILES): CN1C(C)(C)CC(Nc2nc3c(-c4ccc(C(=O)N5CCN(S(C)(=O)=O)CC5)cc4)cnn3c(N)c2-c2ccccc2)CC1(C)C
InChIKey: WOEVJDXDZJWENO-UHFFFAOYSA-N
Target: TEL/KDR (CHIMERIC PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 644.85, ALogP 4.43, HBA 9, HBD 2, PSA 129.17, QED 0.32
Compound (SMILES): CC(C)OP(=O)(OC(C)C)C(Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)P(=O)(OC(C)C)OC(C)C
InChIKey: YLJOVCWVJCDPLN-UHFFFAOYSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Induction of human HMGCR-dCat-ELuc degradation expressed in HEK293 cells assessed as reduction in luciferase activity after 4 hrs by luciferase reporter assay
Measurement: EC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 562.67, ALogP 8.94, HBA 7, HBD 1, PSA 91.29, QED 0.25
Compound (SMILES): CSc1nc2ccccc2n1-c1csc(NC/C(C)=N/N=c2\scc(-c3ccccc3)n2-c2ccccc2)n1
InChIKey: VDNHZWRAJYMIMU-JSYFPCGUSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by EIA
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 567.77, ALogP 7.11, HBA 10, HBD 1, PSA 72.39, QED 0.12
Compound (SMILES): CC(=O)c1cc(C)c(O)c(Cc2[nH]c3ccccc3c2Cc2c(O)c(C)cc(C(C)=O)c2O)c1O
InChIKey: HDCHEJJWHSXQFS-UHFFFAOYSA-N
Target: Hemagglutinin (SINGLE PROTEIN), Influenza A virus (A/Puerto Rico/8/1934(H1N1))
UniProt: P03452
Assay: Binding affinity to Influenza A virus (A/California/04/2009(H1N1)) Hemagglutinin at 1.5625 to 50 uM by SPR assay
Measurement: Kd = 6900 nM (pChEMBL 5.159999847412109)
Descriptors: MW 473.53, ALogP 5.19, HBA 6, HBD 5, PSA 130.85, QED 0.24
Compound (SMILES): c1ccc(-c2nnc(N3CCNCC3)cc2-c2ccncc2)cc1
InChIKey: FLPJMKYUGAMWET-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15759
Assay: Inhibition of human p38beta
Measurement: IC50 = 3310 nM (pChEMBL 5.480000019073486)
Descriptors: MW 317.4, ALogP 2.62, HBA 5, HBD 1, PSA 53.94, QED 0.8
Compound (SMILES): COc1ccc(-c2[nH]c3ccc(C4CCN(C5CCN(C)CC5)CC4)cc3c2C)cc1OC
InChIKey: AULVCMBXTZGHFR-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 447.62, ALogP 5.43, HBA 4, HBD 1, PSA 40.73, QED 0.57
Compound (SMILES): C=CCNC(=O)CCCCCCCOc1cc(OC)cc(C(C)(C)CCCCCC)c1
InChIKey: HRILJFPQDYTDSM-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in HEK cell membrane
Measurement: Ki = 31.2 nM (pChEMBL 7.510000228881836)
Descriptors: MW 431.66, ALogP 6.96, HBA 3, HBD 1, PSA 47.56, QED 0.2
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](NS(=O)(=O)CC4CCC4)CC3)c12
InChIKey: YMIDWRMBEWRZOO-HDJSIYSDSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 378.5, ALogP 2.31, HBA 4, HBD 3, PSA 107.71, QED 0.74
Compound (SMILES): Cc1nccc(-c2cc(-c3nnc[nH]3)c3nc(C)n(-c4ccnc5c(F)ccc(F)c45)c3c2)n1
InChIKey: UKNFKMCRDXQKMX-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length p110alpha/p85alpha using PIP2 as substrate after 30 mins in presence of ATP at 2xKm concentration by TR-FRET assay
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 454.44, ALogP 4.71, HBA 7, HBD 1, PSA 98.06, QED 0.42
Compound (SMILES): CC(=O)N(Cc1cccc(C(F)(F)F)c1)c1ccc(C(=O)NO)cc1
InChIKey: HRSQFBFZBZVSIU-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of N-terminal His-tagged full length human HDAC8 expressed in baculovirus expression system using FAM-RHKK(TF-Ac)-NH2 substrate incubated for 3 hrs by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 352.31, ALogP 3.38, HBA 3, HBD 2, PSA 69.64, QED 0.65
Compound (SMILES): Cn1cc(NC(=O)CCc2nc(-c3ccc(O)cc3)no2)c(C(=O)O)c1
InChIKey: QLDNWJSPEASFTL-UHFFFAOYSA-N
Target: Hydroxycarboxylic acid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDS4
Assay: Agonist activity at GPR109A receptor (unknown origin) expressed in HEK293T cell membranes after 30 mins by [35S]GTPgammaS binding based microbeta scintillation counting analysis
Measurement: EC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 356.34, ALogP 2.05, HBA 7, HBD 3, PSA 130.48, QED 0.62
Compound (SMILES): CC(C)Cc1ccc2c3c1CCN3CCNC2
InChIKey: WUQFMMIZXCMAAQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at 5HT2B receptor (unknown origin)
Measurement: EC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 230.35, ALogP 2.35, HBA 2, HBD 1, PSA 15.27, QED 0.84
Compound (SMILES): Cc1ccc(F)c(-n2ncc3c2CCC[C@H]3NC(=O)c2cc(C(F)(F)F)ccn2)c1
InChIKey: ADJDTKWSVRYLJU-MRXNPFEDSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of recombinant human DHODH using dihydroorotic acid as substrate measured for 68 mins by DCIP based colorimetric assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 418.39, ALogP 4.54, HBA 4, HBD 1, PSA 59.81, QED 0.64
Compound (SMILES): Cc1cc(NS(=O)(=O)c2ccc(Nc3ccnc(SCC(=O)c4ccc(Cl)cc4)n3)cc2)no1
InChIKey: KVWGECLWEKMQRN-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 70150 nM (pChEMBL 4.150000095367432)
Descriptors: MW 516, ALogP 4.95, HBA 9, HBD 2, PSA 127.08, QED 0.18
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc(Cl)c(Nc4ccccc4C)n3)cc2)CC1
InChIKey: ZOXAHJDWPZAVSF-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 = 751 nM (pChEMBL 6.119999885559082)
Descriptors: MW 422.96, ALogP 5.07, HBA 6, HBD 2, PSA 56.32, QED 0.58
Compound (SMILES): CC1CN2CCNCc3ccc(Br)c1c32
InChIKey: NWDWRYLAZDYIBK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2C receptor (unknown origin)
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 267.17, ALogP 2.48, HBA 2, HBD 1, PSA 15.27, QED 0.78
Compound (SMILES): C=CC(=O)N1CCC(Nc2ccc(C(N)=O)c3[nH]c(C)c(C)c23)CC1
InChIKey: GSSZLJQLTKOXPS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 μM), ATP (20 μM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij 35 surfactant and 4 mM DTT in 1.6% DMSO), with a final volume of 30 μL. After incubating at room temperature for 60 min., the reaction was terminated by adding 45 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 control reactions with no enzyme (for 100% inhibition) and controls with no inhibitor (for 0% inhibition). Dose response curves were generated to determine the concentration required for inhibiting 50% of Btk activity (IC50). Compounds were dissolved at 10 mM in DMSO and evaluated at eleven concentrations.
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 340.43, ALogP 2.47, HBA 3, HBD 3, PSA 91.22, QED 0.75
Compound (SMILES): CCC(CC)n1c(-c2ccc(OCc3c(-c4c(Cl)cccc4Cl)noc3C(C)C)cc2F)nc2ccc(C(=O)O)cc21
InChIKey: GFNQRULIGZXHBI-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at human FXR expressed in human HuH7 cells by luciferase reporter gene assay
Measurement: EC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 610.51, ALogP 9.57, HBA 6, HBD 1, PSA 90.38, QED 0.17
Compound (SMILES): Cc1ccc(-c2ncnc(Oc3ccc(C(=N)N)cc3)c2O)cc1
InChIKey: XTSZQTITDROREV-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of activated factor X (unknown origin) using CH3O-CO-D-CHG-Gly-Arg-pNA-AcOH as substrate by fluorescence based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 320.35, ALogP 3.23, HBA 5, HBD 3, PSA 105.11, QED 0.51
Compound (SMILES): COCCOc1nc(N)c2nc(O)n(Cc3ccc(C(=O)NC4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)cc3)c2n1
InChIKey: QKAXNCJSCUTXKM-QCHDJOLESA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: P58681
Assay: Agonist activity at TLR7 in mouse BMDC cells assessed as immunostimulatory activity by measuring increase in IL6 secretion incubated for 18 hrs by ELISA
Measurement: EC50 = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 520.5, ALogP -2.28, HBA 14, HBD 7, PSA 227.56, QED 0.15
Compound (SMILES): C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CC(c2ccc(C(F)(F)F)cc2)C1)C(F)(F)F
InChIKey: LCTSAIASTIGUKO-LBPRGKRZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells by electrophysiology QPatch assay
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 495.44, ALogP 4.68, HBA 4, HBD 0, PSA 63.68, QED 0.57
Compound (SMILES): COc1cc2cc(NC(=O)CCCNCc3ccccc3)c(=O)oc2cc1OC
InChIKey: GNNIJJBFVPDBRB-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholineiodide as substrate measured for every 30 sec for 5 mins by Ellman's method
Measurement: IC50 = 748 nM (pChEMBL 6.130000114440918)
Descriptors: MW 396.44, ALogP 3.32, HBA 6, HBD 2, PSA 89.8, QED 0.43
Compound (SMILES): Cc1c(-c2ccccc2)cccc1-c1cn2nc(CNCCO)cnc2n1
InChIKey: SIYAOZFRXTVXSP-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of human PD-1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 359.43, ALogP 2.85, HBA 6, HBD 2, PSA 75.34, QED 0.52
Compound (SMILES): O=C(N[C@H]1CN(S(=O)(=O)c2ccccc2)C[C@@H]1C(=O)N[C@H]1CCCNC1)c1cc(-c2ccccc2Cl)on1
InChIKey: DRITZQUGSDWNJE-NYDSKATKSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 = 0.442 nM (pChEMBL 9.359999656677246)
Descriptors: MW 558.06, ALogP 2.28, HBA 7, HBD 3, PSA 133.64, QED 0.41
Compound (SMILES): CS(=O)(=O)c1sc(-c2cc(F)cc(F)c2)c2c1[C@H](O)C(F)(F)C2
InChIKey: UWHUYKGCGHNLEP-LBPRGKRZSA-N
Target: Endothelial PAS domain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99814
Assay: Inhibition of HIF2-alpha in human 786-0 cells cells harboring HRE-Luc2P reporter construct incubated for 48 hrs by ONE-Glo EX reagent based luminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 366.36, ALogP 3.32, HBA 4, HBD 1, PSA 54.37, QED 0.83
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2cc(C)ccc2C)cc(OC)c1OC
InChIKey: JDQHNZWJEMDJDN-DKUWSORSSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 16500 nM (pChEMBL 4.78000020980835)
Descriptors: MW 495.62, ALogP 4.08, HBA 6, HBD 2, PSA 89.13, QED 0.57
Compound (SMILES): COc1ccc2c3c1CCN3CCNC2
InChIKey: PWQKYNLQSJZLCJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2C receptor (unknown origin)
Measurement: Ki = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 204.27, ALogP 1.16, HBA 3, HBD 1, PSA 24.5, QED 0.74
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ccc(C(O)c3cccc(C(=O)O)c3)cc2)cc1
InChIKey: MROBOYWUGOBALA-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 0.83 nM (pChEMBL 9.079999923706055)
Descriptors: MW 383.43, ALogP 2.78, HBA 4, HBD 3, PSA 117.69, QED 0.63
Compound (SMILES): CC(c1ncnc2[nH]ccc12)C1CCCCC1.Cl
InChIKey: LMUDLCFADSTXEF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human Lck using TK-substrate-biotin as substrate incubated for 60 mins in presence of ATP by fluorescence method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 229.33, ALogP 3.64, HBA 2, HBD 1, PSA 41.57, QED 0.85
Compound (SMILES): COCc1nc2cnc3cc(-c4c(C)noc4C)c(OC[C@H]4CCNC4)cc3c2n1[C@H](C)c1ccccc1
InChIKey: ZORLJXWXFABTPZ-CTNGQTDRSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human partial length BRD4 BD2 expressed in bacterial expression system assessed as dissociation constant by BROMOscan assay
Measurement: Kd = 0.63 nM (pChEMBL 9.199999809265137)
Descriptors: MW 511.63, ALogP 5.6, HBA 8, HBD 1, PSA 87.23, QED 0.29
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccc(OC)c(OC)c4)c(Cl)c3c2)CC1
InChIKey: OWQIJUNESWBFTP-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 1880 nM (pChEMBL 5.730000019073486)
Descriptors: MW 427.98, ALogP 4.9, HBA 4, HBD 2, PSA 49.52, QED 0.56
Compound (SMILES): Cc1cccc(C(=O)N[C@@H](C(=O)N2CCC3(CC2)C(=O)N(C)C(=O)N3c2ccccc2)C(C)C)c1F
InChIKey: JVAMAQLUVPYFRN-JOCHJYFZSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Autotaxin LPC Cascade Assay: The efficacy of the Examples described herein, as inhibitors of ATX are demonstrated and confirmed by pharmacological in vitro assays. The following assays and their respective methods are carried out with the compounds according to the present invention. Activity possessed by the compounds may be demonstrated in vivo. Those skilled in the art will appreciate that a variety of assay formats may be used to determine the activity of the compounds of this invention.Autotaxin LPC Cascade Assay:Assay Buffer:100 mM Tris-HCl, pH=9500 mM NaCl5 mM MgCl25 mM CaCl20.05% Triton X 100Reagents:Enzyme Source Stock conc Working conc. Final conc. Autotaxin X-Chem 4.6 μM 20 nM 5 nM LPC Sigma L5254 8 mM in assay buffer 400 μM 100 μM Choline Oxidase Sigma C5896 50 U/mL in water 0.8 U/mL 0.1 U/mL HRP Sigma P8375 1000 U/mL in water 8 U/mL 1 U/mL Ampliflu Red Sigma 90101 100 mM in DMSO 400 μM 50 μM.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 494.57, ALogP 3.35, HBA 4, HBD 1, PSA 90.03, QED 0.65
Compound (SMILES): Cc1cc(-c2ccc(=O)n(C)c2)cc2cn(C3CCNCC3)nc12
InChIKey: OMBNJGVWAWYWRQ-UHFFFAOYSA-N
Target: Toll-like receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00206
Assay: Antagonist activity at TLR4 in human PBMC assessed as inhibition of LPS-induced TNFalpha production preincubated for 30 mins followed by LPS addition and measured after 20 hrs by HTRF assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 322.41, ALogP 2.63, HBA 5, HBD 1, PSA 51.85, QED 0.79
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CCCC[C@H]2Cn2ccc(-c3ccc(F)cn3)n2)c1
InChIKey: GGEFNKYUDAADPY-IBGZPJMESA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Antagonist activity at human recombinant OX2R expressed in CHOK1 cells assessed as inhibition of orexin A-induced intracellular Ca2+ release preincubated for 30 mins followed by orexin-A stimulation by Fluo-4AM dye based fluorescence analysis
Measurement: IC50 = 1.64 nM (pChEMBL 8.789999961853027)
Descriptors: MW 445.5, ALogP 3.67, HBA 7, HBD 0, PSA 81.73, QED 0.47
Compound (SMILES): N[C@@]1(C(=O)O)C[C@H]2CNC[C@H]2[C@@H]1CCCB(O)O
InChIKey: XIEAQQGNISCWOO-DKIAZLNASA-N
Target: Arginase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05089
Assay: Inhibition of arginase1 in human cancer patient serum
Measurement: IC50 = 148 nM (pChEMBL 6.829999923706055)
Descriptors: MW 256.11
Compound (SMILES): COC(=O)Cn1nnc(-c2cc(C(C)C)c(O)cc2O)c1-c1ccc(S(C)(=O)=O)cc1
InChIKey: JEWZURJNYGWMQD-UHFFFAOYSA-N
Target: Heat shock protein 75 kDa, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q12931
Assay: Inhibition of TRAP1 (unknown origin)
Measurement: IC50 = 15974 nM (pChEMBL 4.800000190734863)
Descriptors: MW 445.5, ALogP 2.72, HBA 9, HBD 2, PSA 131.61, QED 0.55
Compound (SMILES): CC(C)c1onc(-c2ccccc2Cl)c1COc1ccc(CCCC(=O)O)cc1
InChIKey: VLTXEUCGBCOLBD-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Activation of human PPAR-delta LBD expressed in HEK293T cells assessed as induction of receptor activation incubated for 12 to 14 hrs by luciferase reporter gene assay
Measurement: EC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 413.9, ALogP 6.1, HBA 4, HBD 1, PSA 72.56, QED 0.46
Compound (SMILES): COc1ccc2nc(NC(=O)c3ccc(OCc4ccccc4)cc3)sc2c1
InChIKey: RFEDIUPOYRAACU-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Inhibition of SCD in human H2009 cells non-expressing CYP4F11 assessed as reduction in cell viability incubated for 96 hrs by cell titer Glo reagent based assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 390.46, ALogP 5.14, HBA 5, HBD 1, PSA 60.45, QED 0.5
Compound (SMILES): CCCCCc1cc(OC)cc(OCCCCCCCCCCC(=O)NCCO)c1
InChIKey: YOODCUVAOWQGPD-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in HEK cell membrane
Measurement: Ki = 33.2 nM (pChEMBL 7.480000019073486)
Descriptors: MW 421.62, ALogP 5.43, HBA 4, HBD 2, PSA 67.79, QED 0.29
Compound (SMILES): O=C(c1cc2ccccc2o1)N1CCCN(Cc2ccccc2)CC1
InChIKey: OMVJEGIHFMHTLM-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-Di-o-tolylguanidine from sigma-2 receptor in rat liver membranes after 120 mins by scintillation counting method
Measurement: Ki = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 334.42, ALogP 3.78, HBA 3, HBD 0, PSA 36.69, QED 0.73
Compound (SMILES): Cc1nsc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)F)cccn3n2)n1
InChIKey: QRNBVQVYYYFGKJ-DABQJJPHSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 439.47, ALogP 3.16, HBA 9, HBD 1, PSA 80.47, QED 0.65
Compound (SMILES): CN1N=CC2C1C(O)=C(C(=O)NC13CC4CC(CC(O)(C4)C1)C3)C(=O)N2CCCCF
InChIKey: JSKGAXNBYBJWRU-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55,940 from recombinant human CB2R expressed in HEK293 cell membranes
Measurement: Ki = 18.9 nM (pChEMBL 7.71999979019165)
Descriptors: MW 434.51, ALogP 1.26, HBA 6, HBD 3, PSA 105.47, QED 0.43
Compound (SMILES): Cc1ncccc1Oc1cc(Sc2ccccn2)cnc1Nc1nc(C2CCN(S(C)(=O)=O)CC2)ns1
InChIKey: RXEPTVLJQLRTNX-UHFFFAOYSA-N
Target: Hexokinase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P35557
Assay: Activation of glucokinase (unknown origin) in presence of 4% human serum albumin
Measurement: EC50 = 684 nM (pChEMBL 6.170000076293945)
Descriptors: MW 555.71, ALogP 4.86, HBA 11, HBD 1, PSA 123.09, QED 0.32
Compound (SMILES): O=C(CCCc1ccccc1)C(=O)NCCc1ccc(Oc2ccc(C(F)(F)F)cn2)cc1
InChIKey: DZHZISUSQMPBJQ-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 456.46, ALogP 5.14, HBA 4, HBD 1, PSA 68.29, QED 0.43
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CNC(C)(C)C(=O)O)cc2Cl)cccc1-c1ccccc1
InChIKey: YZPKZNFXWGTUGO-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of human C-terminal Ig-Fc-tagged PD1 (Leu25 to Gln167 residues) expressed in HEK293 cells/human C-terminal epitope-His-tagged PDL1 (Phe19 to Arg238 residues) expressed in HEK293 cells protein-protein interaction preincubated for 15 mins with PDL1 followed by PD1 addition and measured after 15 mins by APC-labeled anti-His antibody/Eu-labeled anti-human IgG based HTRF assay
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 555.07, ALogP 7.3, HBA 5, HBD 2, PSA 91.58, QED 0.2
Compound (SMILES): O=C1[C@@H]2[C@H]3CC[C@H](C3)[C@@H]2C(=O)N1CCCCCCN1CCN(c2cccc(Cl)c2Cl)CC1
InChIKey: MIVAZVMVBOSSKJ-MTIDIVMFSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5HT1A receptor expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: Ki = 32 nM (pChEMBL 7.5)
Descriptors: MW 478.46, ALogP 4.71, HBA 4, HBD 0, PSA 43.86, QED 0.4
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(Cc1cccnc1)CC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: QPJJHFXCAQXJRK-VEEOACQBSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 608.79, ALogP 6.42, HBA 7, HBD 2, PSA 113.1, QED 0.16
Compound (SMILES): CC(C)(O)CNC(=O)c1nc(C(=O)N2CCC(F)(F)CC2)c(-c2ccc(S(=O)(=O)NC(C)(C)CF)c(Cl)c2Cl)s1
InChIKey: NXOMRNWMDOOLKC-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 645.55, ALogP 4.52, HBA 7, HBD 3, PSA 128.7, QED 0.37
Compound (SMILES): O=c1sn(-c2cccc3ccccc23)c(=O)n1Cc1cccc(O)c1
InChIKey: CXWOEXBOSLHVIG-UHFFFAOYSA-N
Target: Sortase A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q9S446
Assay: Inhibition of Staphylococcus aureus SrtA delta N24 mutant expressed in Escherichia coli BL21 (DE3) using Abz-LPATG-Dnp substrate incubated for 20 mins by FRET-based assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 350.4, ALogP 2.97, HBA 6, HBD 1, PSA 64.23, QED 0.62
Compound (SMILES): CN(C1CCN(c2n[nH]c(N)n2)CC1)[C@H](COc1ccc(Cl)cc1)Cc1ccc(Cl)cc1
InChIKey: TWHZUPHLCCRRBF-FQEVSTJZSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of full length recombinant C-terminal His-taged human CHIT1 expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N''-diacetylchitotrioside as substrate incubated for 60 mins under shaking condition by microplate fluorometry analysis
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 475.42, ALogP 4.28, HBA 6, HBD 2, PSA 83.3, QED 0.51
Compound (SMILES): COc1cc(N2CC(NC(=O)c3ccc4nn(C)c(C)c4c3N)C2)c(Cl)cn1
InChIKey: OIQKUMPIYFHKIE-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Positive allosteric modulation of human muscarinic M4 receptor expressed in CHO cells co-expressing Gqi5 assessed as increase in acetylcholine-induced calcium mobilization
Measurement: EC50 = 148 nM (pChEMBL 6.829999923706055)
Descriptors: MW 400.87, ALogP 2.14, HBA 7, HBD 2, PSA 98.3, QED 0.65
Compound (SMILES): Cc1nc(-c2cc(C(F)(F)F)ccc2[C@H]2CCOc3cc(S(=O)(=O)Nc4nccs4)ccc32)co1
InChIKey: KQWOBWMNPNSGDQ-QGZVFWFLSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin) expressed in HEK293 cells assessed as reduction in veratridine-induced depolarization preincubated for 15 to 20 mins followed by veratridine stimulation by 1X red membrane potential dye based FLIPR assay
Measurement: IC50 = 629 nM (pChEMBL 6.199999809265137)
Descriptors: MW 521.54, ALogP 5.84, HBA 7, HBD 1, PSA 94.32, QED 0.35
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@H]3CN(S(=O)(=O)c4ccccc4)C[C@@H]3C(=O)N[C@H]3CCCN(C)C3)cc2c1
InChIKey: QPXGPLCMDWOSJQ-XTJBDQBJSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 = 0.448 nM (pChEMBL 9.350000381469727)
Descriptors: MW 523.66, ALogP 2.11, HBA 5, HBD 3, PSA 114.61, QED 0.46
Compound (SMILES): Cc1cnc(NS(=O)(=O)c2ccc(Nc3ccnc(SCC(=O)c4ccc(C(F)(F)F)cc4)n3)cc2)nc1
InChIKey: OEUIIKNJVOUWTK-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 59060 nM (pChEMBL 4.230000019073486)
Descriptors: MW 560.58, ALogP 5.11, HBA 9, HBD 2, PSA 126.83, QED 0.16
Compound (SMILES): O=C(CCc1ccccc1Cl)C(=O)NCCc1ccccc1
InChIKey: RMOHFFYQGRHIJF-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 315.8, ALogP 3.2, HBA 2, HBD 1, PSA 46.17, QED 0.8
Compound (SMILES): Cc1c(NC(=O)Nc2ccc(C(=O)O)cc2)oc2ccccc12
InChIKey: IIEWIZUCBAJMCX-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 310.31, ALogP 4.08, HBA 3, HBD 3, PSA 91.57, QED 0.68
Compound (SMILES): COc1cccc(COc2ccc(C(=O)N[C@H](C(=O)NCc3ccc(NC(=N)N)cc3)c3ccc(OCc4ccccc4)cc3)cc2)c1.O=C(O)C(F)(F)F
InChIKey: IOWGAVFOYNZLTB-XLQCLRHOSA-N
Target: Genome polyprotein (SINGLE PROTEIN), West Nile virus
UniProt: P06935
Assay: Inhibition of West Nile virus NS2B-NS3 protease expressed in Escherichia coli BL21 lambda (DE3) cells using Abz-Gly-Leu-Lys-Arg-Gly-Gly-3-(NO2)Tyr as substrate preincubated for 15 mins followed by substrate addition measured for 15 mins by fluorimetric analysis
Measurement: IC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 643.74, ALogP 5.95, HBA 6, HBD 5, PSA 147.79, QED 0.07
Compound (SMILES): Cc1ccc(CCNC(=O)C(=O)CCCc2ccccc2)cc1
InChIKey: GCPXYBVMISMYPI-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 309.41, ALogP 3.25, HBA 2, HBD 1, PSA 46.17, QED 0.76
Compound (SMILES): Cc1nc2c(-c3nnc[nH]3)cc(-c3ccnc(N)c3)cc2n1-c1ccnc2c(F)ccc(F)c12
InChIKey: QUDFJWGWCAJQGK-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged p110beta/human recombinant full-length untagged p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate after 30 mins in presence of ATP at 2xKm concentration by TR-FRET assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 454.44, ALogP 4.59, HBA 7, HBD 2, PSA 111.19, QED 0.4
Compound (SMILES): C[C@H](CCCOc1ccccc1Cn1c(Cl)cnc1-c1ccc(C(F)(F)F)cc1)CC(=O)O
InChIKey: YBDMLCZZFCXIHA-MRXNPFEDSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Transactivation of GAL4-fused human PPARalpha expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 480.91, ALogP 6.54, HBA 4, HBD 1, PSA 64.35, QED 0.33
Compound (SMILES): O=C(c1c[nH]c2ccccc12)N1CCC(N2CCc3ccccc3C2)C1
InChIKey: LACZYCKWRKMDPU-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H](+)-DTG from recombinant sigma 2 receptor (unknown origin) expressed in baculovirus infected Sf9 cell membranes after 1.5 hrs by scintillation counting analysis
Measurement: Kd > 1000 nM (pChEMBL 6)
Descriptors: MW 345.45, ALogP 3.44, HBA 2, HBD 1, PSA 39.34, QED 0.77
Compound (SMILES): Cc1ccc(CNc2cnn(C)c(=O)c2Cl)cc1
InChIKey: OTFSEPHUVQXEQQ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 (1) (unknown origin) N-terminal bromodomain by TR-FRET assay
Measurement: IC50 = 12589.25 nM (pChEMBL 4.900000095367432)
Descriptors: MW 263.73, ALogP 2.35, HBA 4, HBD 1, PSA 46.92, QED 0.92