lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H](NC(=O)Cn1nc2ccc(F)cn2c1=O)c1ccc(Cl)c(F)c1
InChIKey: AHVUNPDUKVXUJI-VIFPVBQESA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 366.75, ALogP 2.31, HBA 5, HBD 1, PSA 68.4, QED 0.77
Compound (SMILES): C=CC(=O)N[C@H]1COC[C@H]1Nc1ncc2cc(-c3cc(OC)cc(OC)c3)c(=O)n(C)c2n1
InChIKey: KZGOHFREJPYORJ-RBUKOAKNSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) expressed in human Huh7 cells assessed as autophosphorylation after 1 hr incubation measured by Mesoscale discovery (MSD) assay
Measurement: IC50 = 685 nM (pChEMBL 6.159999847412109)
Descriptors: MW 451.48, ALogP 1.49, HBA 9, HBD 2, PSA 116.6, QED 0.52
Compound (SMILES): COc1ccc(OCCNCC2(F)CCN(C(=O)c3ccc(Cl)c(Cl)c3)CC2)cc1
InChIKey: GCGYVRDXSGMVJW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation after 15 mins by Alphalisa assay
Measurement: EC50 = 47.86 nM (pChEMBL 7.320000171661377)
Descriptors: MW 455.36, ALogP 4.61, HBA 4, HBD 1, PSA 50.8, QED 0.59
Compound (SMILES): N#Cc1ccccc1C(=O)NCCCC[C@H](NC(=O)c1cncs1)c1ncc(-c2ccc3ccccc3c2)[nH]1
InChIKey: AHNPIQKMSCPRDA-VWLOTQADSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant full length FLAG-tagged HDAC3 expressed in HEK293F cells in using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 534.65, ALogP 5.63, HBA 6, HBD 3, PSA 123.56, QED 0.2
Compound (SMILES): Cc1ccccc1-c1cn(C)c(=O)c2[nH]c(C(=O)NCc3ccc(C(=O)Nc4ccccc4N)cc3)cc12
InChIKey: WKYVRHSREOYIFK-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 148.8 nM (pChEMBL 6.829999923706055)
Descriptors: MW 505.58, ALogP 4.61, HBA 5, HBD 4, PSA 122.01, QED 0.25
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cnccn2)CC1
InChIKey: PCQQITDIAVWGLB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human recombinant 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation levels incubated for 15 mins by Alphalisa assay
Measurement: EC50 = 4.898 nM (pChEMBL 8.3100004196167)
Descriptors: MW 410.85, ALogP 2.88, HBA 5, HBD 1, PSA 67.35, QED 0.71
Compound (SMILES): COc1ccc(S(=O)(=O)N2C[C@@H](NS(=O)(=O)c3ccc(-c4ccccc4)cc3)C[C@@H]2C(=O)O)cc1
InChIKey: WJTQOAHAJQKSTM-WMZHIEFXSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 incubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 8400 nM (pChEMBL 5.079999923706055)
Descriptors: MW 516.6, ALogP 2.56, HBA 6, HBD 2, PSA 130.08, QED 0.47
Compound (SMILES): C[C@@H](c1cccc(CN)c1)n1cc(Cl)cc(C(N)=O)c1=N.Cl
InChIKey: PIRKVXKOMRREFI-FVGYRXGTSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000300bCl ADRA1B
Measurement: Ki > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 304.78, ALogP 1.79, HBA 4, HBD 3, PSA 97.89, QED 0.8
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nnc(SCC(=O)Nc3ccc(Br)cc3)o2)cc1
InChIKey: CNVIWWXAJYNTGW-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 671.2 nM (pChEMBL 6.170000076293945)
Descriptors: MW 469.34, ALogP 2.88, HBA 7, HBD 2, PSA 128.18, QED 0.53
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc(Cl)ccc2OC)[nH]1
InChIKey: GGIFGGZXDOWFGD-RPWUZVMVSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 < 0.2 nM (pChEMBL 9.699000358581543)
Descriptors: MW 529.13, ALogP 5.95, HBA 5, HBD 2, PSA 87.32, QED 0.31
Compound (SMILES): COc1cccc(-c2cncc3[nH]c(-c4n[nH]c5ccc(-c6cncc(NC(=O)C7CCCCC7)c6)nc45)nc23)c1
InChIKey: HTAKNIDVRHLBRP-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 544.62, ALogP 6.15, HBA 7, HBD 3, PSA 134.36, QED 0.23
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc(C(C)C)ccc2OC)[nH]1
InChIKey: CTWAHLUSZXHMHD-SXOMAYOGSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 536.76, ALogP 6.42, HBA 5, HBD 2, PSA 87.32, QED 0.27
Compound (SMILES): CC(C)CC(=O)Nc1cncc(-c2cc3c(-c4cc5c(-c6cccs6)nccc5[nH]4)n[nH]c3cn2)c1
InChIKey: XTSIWTVFIHGEOP-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 392 nM (pChEMBL 6.409999847412109)
Descriptors: MW 493.6, ALogP 6.28, HBA 6, HBD 3, PSA 112.24, QED 0.25
Compound (SMILES): NC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCC1CCN(Cc2ccccc2)CC1
InChIKey: WCUGNCQJDCCMLE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholineiodide as substrate incubated for 10 mins by Ellman's method
Measurement: IC50 = 12700 nM (pChEMBL 4.900000095367432)
Descriptors: MW 491.62, ALogP 3.94, HBA 7, HBD 2, PSA 110.44, QED 0.47
Compound (SMILES): Cc1n[nH]c2ccc(-c3cncc(N4CCC(O)CC4)n3)cc12
InChIKey: FWNGIOZXEPPEBU-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 4261 nM (pChEMBL 5.369999885559082)
Descriptors: MW 309.37, ALogP 2.29, HBA 5, HBD 2, PSA 77.93, QED 0.76
Compound (SMILES): CC(C)(C)c1ccc(C#Cc2cc(-c3nn(-c4nc(C(=O)O)cs4)c(CC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)ccc2F)s1
InChIKey: OUVZWDKJHZAZJK-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 507 nM (pChEMBL 6.289999961853027)
Descriptors: MW 692.84, ALogP 6.92, HBA 8, HBD 2, PSA 128.17, QED 0.17
Compound (SMILES): Cc1ccc(-c2nccc3[nH]c(-c4n[nH]c5ccc(-c6cncc(N)c6)cc45)nc23)s1
InChIKey: GTAFJBCMRPSYOK-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 423.51, ALogP 5.18, HBA 6, HBD 3, PSA 109.16, QED 0.36
Compound (SMILES): COc1ccc(Nc2cc(-c3ccccc3)cc3c2c(=O)[nH]c2c(OC)c(OC)ccc23)cc1
InChIKey: QTPANJZDIMFYLC-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 (107 to 449 residues) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 expressed in Escherichia coli expression system as substrate incubated for 15 mins followed by substrate addition and measured after 2 to 4 hrs by fluorescence based assay
Measurement: IC50 = 20500 nM (pChEMBL 4.690000057220459)
Descriptors: MW 452.51, ALogP 6.12, HBA 5, HBD 2, PSA 72.58, QED 0.3
Compound (SMILES): CC(C)n1nc2c(c1-c1ccc(F)cc1)CCNCC2
InChIKey: RBYJHELKTYHZNG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-ketanserin from human 5-HT2C receptor by competitive radioligand binding assay
Measurement: Ki = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 273.36, ALogP 2.96, HBA 3, HBD 1, PSA 29.85, QED 0.91
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OCc1cccc(Cl)c1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: FFKAGSMMGAVCAA-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human butyrylcholinesterase in plasma using butyrylthiocholineiodide as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured at 2 mins interval by Ellman's method
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 446.91, ALogP 5.32, HBA 4, HBD 0, PSA 40.8, QED 0.4
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(C(=O)/C=C/CN(C)C)C3)nc1-c1cnn(C(C)C)c1
InChIKey: SURRDPSGERGIIM-VOTSOKGWSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 459.6, ALogP 3.98, HBA 7, HBD 1, PSA 79.18, QED 0.54
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(C)(C)F
InChIKey: RMHSPVDIAHEXNT-NSYGIPOTSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: MCF-7 ER Down-Regulation Assay: The ability of compounds to down-regulate Estrogen Receptor (ER) numbers was assessed in a cell based immuno-fluorescence assay using the MCF-7 human ductal carcinoma breast cell line. MCF-7 cells were revived directly from a cryovial (approx 5×106 cells) in Assay Medium (phenol red free Dulbecco's Modified Eagle's medium (DMEM); Sigma D5921) containing 2 mM L-Glutamine and 5% (v/v) Charcoal/Dextran treated foetal calf serum. Cells were syringed once using a sterile 18G×1.5 inch (1.2×40 mm) broad gauge needle and cell density was measured using a Coulter Counter (Beckman). Cells were further diluted in Assay Medium to a density of 3.75×104 cells per mL and 40 μL per well added to transparent bottomed, black, tissue culture-treated 384 well plates (Costar, No. 3712) using a Thermo Scientific Matrix WellMate or Thermo Multidrop. Following cell seeding, plates were incubated overnight at 37° C., 5% CO2 (Liconic carousel incubator). Test data was generated using the LabCyte Echo model 555 compound reformatter which is part of an automated workcell (Integrated Echo 2 workcell). Compound stock solutions (10 mM) of the test compounds were used to generate a 384 well compound dosing plate (Labcyte P-05525-CV1). 40 μL of each of the 10 mM compound stock solutions was dispensed into the first quadrant well and then 1:100 step-wise serial dilutions in DMSO were performed using a Hydra II (MATRIX UK) liquid handling unit to give 40 μL of diluted compound into quadrant wells 2 (0.1 mM), 3 (1 μM) and 4 (0.01 μM), respectively. 40 μL of DMSO added to wells in row P on the source plate allowed for DMSO normalisation across the dose range. To dose the control wells 40 μL of DMSO was added to row O1 and 40 μL of 100 μM fulvestrant in DMSO was added to row O3 on the compound source plate.
Measurement: IC50 = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 468.6, ALogP 4.5, HBA 5, HBD 2, PSA 60.08, QED 0.51
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)Cn2nc3cccnn3c2=O)cc1F
InChIKey: GJNXMHUSLXXQOF-NSHDSACASA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 329.33, ALogP 1.22, HBA 6, HBD 1, PSA 81.29, QED 0.78
Compound (SMILES): COc1cc(SCc2ccc(CN(C)C)o2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: IVWSMDDTFYCVFZ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human N-terminal GST-tagged ALK G1202R mutant (1058 to 1620 residues) expressed in baculovirus expression system using Srctide as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 589.14, ALogP 5.94, HBA 10, HBD 3, PSA 121.62, QED 0.17
Compound (SMILES): Oc1ccc(C(=C(Cn2ccnc2)c2ccc(O)c(F)c2)c2ccc(O)cc2)cc1
InChIKey: IXOMVICDLBGZFI-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Displacement of ES2 from recombinant human ER-beta incubated for 2 hrs by fluorescence based assay
Measurement: EC50 = 56.3 nM (pChEMBL 7.25)
Descriptors: MW 402.43, ALogP 4.8, HBA 5, HBD 3, PSA 78.51, QED 0.42
Compound (SMILES): CC(C)(C)OC(=O)NCCn1[se]c2ccccc2c1=O
InChIKey: VKFZXEANTNEIKG-UHFFFAOYSA-N
Target: Metallo-beta-lactamase type 2 (SINGLE PROTEIN), Klebsiella pneumoniae
UniProt: C7C422
Assay: Inhibition of wild type N-terminal His6-tagged Klebsiella pneumoniae NDM-1 expressed in Escherichia coli BL21 assessed as inhibition constant using nitrocefin as substrate measured after 30 mins
Measurement: Ki = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 341.27
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(C#CC#Cc3cnc([C@@H]4CCCN4C(=O)[C@H](NC(=O)OC)c4ccccc4)[nH]3)c(-c3cccc(F)c3F)c2)[nH]1)C(C)C
InChIKey: CTJASFNLKKZKMK-QTWSNBRVSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 1a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.028 nM (pChEMBL 10.550000190734863)
Descriptors: MW 856.93, ALogP 6.95, HBA 8, HBD 4, PSA 174.64, QED 0.11
Compound (SMILES): Cc1cc(C(=O)O)nc(N2CCC(COc3ccc(F)cc3C(F)(F)F)C2)n1
InChIKey: SGMJEWLLXUDDIT-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: Displacement of FITC-diclofenac from human plasma derived TTR measured after overnight incubation by fluorescence polarization assay
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 399.34, ALogP 3.55, HBA 5, HBD 1, PSA 75.55, QED 0.78
Compound (SMILES): COc1ccc(OC)c2c1c(OC)cc1c(=O)cc(-c3ccc4ncccc4c3)oc12
InChIKey: SDAWPFZDSWMYJS-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethoxyresorufin as substrate after 50 mins in presence of NADP+ by EROD assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 413.43, ALogP 5.19, HBA 6, HBD 0, PSA 70.79, QED 0.38
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cccnc2OC)[nH]1
InChIKey: KUNOZPWIEWXRCI-PKTZIBPZSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 495.67, ALogP 4.69, HBA 6, HBD 2, PSA 100.21, QED 0.39
Compound (SMILES): C[C@H](NC(=O)Cn1nc2cc(C3CC3)cnn2c1=O)c1ccc(Cl)c(F)c1
InChIKey: FGELCXMDRNZDIQ-JTQLQIEISA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 389.82, ALogP 2.44, HBA 6, HBD 1, PSA 81.29, QED 0.73
Compound (SMILES): O=C(Nc1cnn(-c2csc(C(=O)NC3COC3)c2)c1)Nc1ccccc1Cl
InChIKey: FPVKFPPNOMNINZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: Inhibition of JNK1 (unknown origin) using ATF2 as substrate after 22 mins in presence of ATP by HTRF assay
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 417.88, ALogP 3.36, HBA 6, HBD 3, PSA 97.28, QED 0.59
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cccc(Cl)c2OC)[nH]1
InChIKey: OBVIXKUIQHYXKO-VWNXMTODSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 529.13, ALogP 5.95, HBA 5, HBD 2, PSA 87.32, QED 0.31
Compound (SMILES): COc1ccc(N2CCOCC2)c2sc(NC(=O)N3CCC(CF)CC3)nc12
InChIKey: FFLSMIVBQPLWHK-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]-DPCPX from recombinant human A1 receptor expressed in CHO-K1 cells incubated for 70 mins by liquid scintillation counting method
Measurement: Ki = 1198 nM (pChEMBL 5.920000076293945)
Descriptors: MW 408.5, ALogP 3.35, HBA 6, HBD 1, PSA 66.93, QED 0.84
Compound (SMILES): CN(C)Cc1nc2ccc(Nc3ncc(Cl)c(Nc4ccccc4C(=O)N(C)C)n3)cc2[nH]1
InChIKey: HHJKVSLHPQFAQK-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of human N-terminal GST-fused ALK G1202R mutant cytoplasmic domain (1058 to 1620 residues) expressed in baculovirus infected Sf21 insect cells using Srctide as substrate measured after 1 hr by mobility shift assay
Measurement: IC50 = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 464.96, ALogP 4.26, HBA 7, HBD 3, PSA 102.07, QED 0.38
Compound (SMILES): O=C(CNC(=O)/C(Cc1ccc(O)c(Br)c1)=N/O)NO
InChIKey: NYBYLHAKGMXBDP-RIYZIHGNSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant full length C-terminal FLAG-tagged human HDAC2 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 9210 nM (pChEMBL 5.039999961853027)
Descriptors: MW 346.14, ALogP 0.15, HBA 6, HBD 5, PSA 131.25, QED 0.22
Compound (SMILES): O=C(NC1CC2CCC(C1)N2Cc1cccnc1)c1ccc2ccccc2c1
InChIKey: GAXNFSNKLNLTML-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserin from rat cerebral cortex 5HT2A receptor measured after 20 mins by liquid scintillation counter method
Measurement: Ki = 484 nM (pChEMBL 6.320000171661377)
Descriptors: MW 371.48, ALogP 4.16, HBA 3, HBD 1, PSA 45.23, QED 0.75
Compound (SMILES): O=C1N2C[C@@H](CC[C@H]2F)N1OS(=O)(=O)[O-].[Na+]
InChIKey: UIJIKXQAJBMNIR-JBUOLDKXSA-M
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 240.21, ALogP -0.08, HBA 4, HBD 1, PSA 87.15, QED 0.54
Compound (SMILES): O=C(Nc1cncc(-c2cnc3[nH]nc(-c4cc5c(-c6ccccc6F)cncc5[nH]4)c3c2)c1)C1CC1
InChIKey: ZJMULPMURRDTSB-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 489.51, ALogP 5.72, HBA 5, HBD 3, PSA 112.24, QED 0.29
Compound (SMILES): CN(C)CC/C=C/C(=O)Nc1ccc(C(=O)N2CCCC(C(=O)Nc3ncc(SCc4ncc(C(C)(C)C)o4)s3)C2)cc1
InChIKey: IFAKQBBVXIIUEC-UXBLZVDNSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 624.83, ALogP 5.66, HBA 9, HBD 2, PSA 120.67, QED 0.21
Compound (SMILES): FC(F)(F)c1cc2cc(c1)OC/C=C\CCNc1nc(nc(-c3cccc(C(F)(F)F)n3)n1)N2
InChIKey: IFMMQRPFAUETKS-IWQZZHSRSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of wild type IDH2 (unknown origin) assessed as reduction in NADPH production using sodium(D)-isocitrate and NADP as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 482.39, ALogP 5.47, HBA 7, HBD 2, PSA 84.85, QED 0.35
Compound (SMILES): COc1ccc(-n2nnc3cnc(N[C@@H]4CC[C@H](N)C4)nc32)cc1
InChIKey: OSHLPUOBFBCDRP-WDEREUQCSA-N
Target: Mitogen-activated protein kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16659
Assay: Inhibition of recombinant full length His6-GST fusion tagged ERK3 (1 to 721 residues) (unknown origin) using MK5 K51A mutant as substrate by ADP-Glo assay
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 325.38, ALogP 1.51, HBA 8, HBD 2, PSA 103.77, QED 0.75
Compound (SMILES): CN[C@@H](C)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)Nc1cc2c(N[C@H]3CC[C@H](Nc4ncnc5cc(OC)c(NC(=O)[C@@H]6CCCN6C(=O)[C@@H](NC(=O)[C@H](C)NC)C(C)(C)C)cc45)CC3)ncnc2cc1OC)C(C)(C)C
InChIKey: YIZXATJRZDXIBK-ZOGJLHJXSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 43600 nM (pChEMBL 4.360000133514404)
Descriptors: MW 1051.31
Compound (SMILES): Cc1cc(C(=O)O)nc(N2CC[C@H](COc3ccccc3C(F)(F)F)C2)n1
InChIKey: YNIAPSNMAZHUHD-LBPRGKRZSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: Displacement of FITC-diclofenac from human plasma derived TTR measured after overnight incubation by fluorescence polarization assay
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 381.35, ALogP 3.41, HBA 5, HBD 1, PSA 75.55, QED 0.86
Compound (SMILES): COc1ccc(-c2cc(C(=O)NC3CCCCCC3)c(OCc3ccc(F)cc3)nc2C)cc1
InChIKey: KHBYMJQCFRCSSX-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of FAAH in human U937 cells using [ethanolamine-1-3H]AEA as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 462.57, ALogP 6.24, HBA 4, HBD 1, PSA 60.45, QED 0.42
Compound (SMILES): COc1cc2nc3ccccc3c(Nc3ccc(C(=O)NO)cc3)c2c(OC)c1OC
InChIKey: RXYDUXPNMOBQTR-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC5 (656 to 1122 residues) expressed in baculovirus infected Sf9 insect cells using fluorogenic HDAC 2A substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 4230 nM (pChEMBL 5.369999885559082)
Descriptors: MW 419.44, ALogP 4.28, HBA 7, HBD 3, PSA 101.94, QED 0.24
Compound (SMILES): O=C(Nc1cccnc1)c1n[nH]c2ncc(-c3cccnc3)cc12
InChIKey: CDMSDNMTTKWFNB-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 916 nM (pChEMBL 6.039999961853027)
Descriptors: MW 316.32, ALogP 2.67, HBA 5, HBD 2, PSA 96.45, QED 0.61
Compound (SMILES): C[C@H]1CN(CC[C@H]2CC[C@H](N3C(=O)CC4(CCCC4)CC3=O)CC2)CCc2ccc(Cl)cc21
InChIKey: DTQQYFXMBRLANH-HFMPRLQTSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]methyl-spiperone from recombinant human D3 receptor expressed in CHO cells
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 471.09, ALogP 5.96, HBA 3, HBD 0, PSA 40.62, QED 0.51
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3cccnc3)CC2)cc1.O=C(O)C(=O)O
InChIKey: RADSTKUIYGICJB-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D4 receptor by liquid scintillation counting
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 313.42, ALogP 3.37, HBA 3, HBD 0, PSA 19.37, QED 0.76
Compound (SMILES): C=C(C)COc1ccc2occc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: OGHDGEGNAGESEA-YLAFAASESA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 151.36 nM (pChEMBL 6.820000171661377)
Descriptors: MW 257.33, ALogP 3.45, HBA 3, HBD 1, PSA 48.39, QED 0.83
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(O[C@@H]2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)c(F)c1
InChIKey: BECZMWHGUIMQOD-LOFRFSAXSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin)
Measurement: IC50 = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 563.08, ALogP 6.28, HBA 6, HBD 3, PSA 95.17, QED 0.21
Compound (SMILES): CC(C)(O)CNC(=O)[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: QYNFVEHOGUQHMA-NHCICSSKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human whole blood assessed as inhibition of anti-CD3/anti-CD28 monoclonal antibodies-stimulated IL-17A production measured by ELISA
Measurement: EC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 613.57, ALogP 5.64, HBA 4, HBD 2, PSA 83.47, QED 0.33
Compound (SMILES): O=C(NO)c1cccc(Nc2c3ccccc3nc3ccccc23)c1
InChIKey: IGGDIHCMNIOYJN-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC5 (656 to 1122 residues) expressed in baculovirus infected Sf9 insect cells using fluorogenic HDAC 2A substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 20760 nM (pChEMBL 4.679999828338623)
Descriptors: MW 329.36, ALogP 4.25, HBA 4, HBD 3, PSA 74.25, QED 0.3
Compound (SMILES): CCC[C@](C)(O)[C@H]1CC23C=C[C@]1(OC)[C@H]1Oc4c(O)ccc5c4[C@]12CCN(C)[C@@H]3C5
InChIKey: CAHCBJPUTCKATP-AXAGGYKYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]HS665 from KOR in guinea pig brain membranes measured after 45 mins by scintillation counting method
Measurement: Ki = 1.443 nM (pChEMBL 8.84000015258789)
Descriptors: MW 411.54, ALogP 3.16, HBA 5, HBD 2, PSA 62.16, QED 0.75
Compound (SMILES): Cc1cc(F)cc(C)c1Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NCc3ccc(C(=O)NO)cc3)cc12
InChIKey: ZGISYTAPMAPSIK-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 1 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 305 nM (pChEMBL 6.519999980926514)
Descriptors: MW 612.66, ALogP 5.36, HBA 7, HBD 5, PSA 145.68, QED 0.12
Compound (SMILES): Cc1cc(NC2CCc3ccc(Br)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: WSMWEZWUWJDREU-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of N-terminal His6-tagged human DHODH expressed in Escherichia coli BL21 using L-DHO as substrate and CoQ as co-substrate by DCIP dye based spectrophotometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 422.28, ALogP 4.28, HBA 5, HBD 1, PSA 55.11, QED 0.69
Compound (SMILES): C[C@H](NC(=O)[C@@H]1C[C@H]2C[C@H]2N1C(=O)Cn1nc(C(N)=O)c2cccnc21)c1cccc(Cl)c1F
InChIKey: SOXWMGIJZSBBEW-SONRMIBWSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of CFD in 50% human whole blood assessed as reduction in alternate complement pathway-mediated MAC formation pre-incubated for 15 mins followed by zymosan suspension addition and measured after 40 mins by ELISA
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 484.92, ALogP 2.19, HBA 6, HBD 2, PSA 123.21, QED 0.55
Compound (SMILES): COCC(=O)NC[C@@H]1CNCCO[C@H]1c1ccc(Cl)c(Cl)c1.Cl
InChIKey: SUHUBWRSUIAZNT-JDOFTSHGSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Inhibition of human DAT expressed in CHO-K1 cells assessed as inhibition of [3H]-dopamine reuptake measured after 60 mins by Microscintillation counting analysis
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 347.24, ALogP 2.03, HBA 4, HBD 2, PSA 59.59, QED 0.86
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCNC(=O)c3cccc(S(N)(=O)=O)c3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: BQYCUVSPDUOPHX-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]-HEMADO from human A3 receptor stably expressed in CHO cell membranes by radioligand competitive binding assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 572.61, ALogP 1.54, HBA 10, HBD 4, PSA 196.57, QED 0.21
Compound (SMILES): C[C@](O)(Cn1cc([N+](=O)[O-])cn1)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1
InChIKey: LDIGXZUZJMDBIM-AWEZNQCLSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Human Androgen Receptor (hAR) Ligand Binding Domain (LBD) Affinity Assay: Methods: hAR-LBD (633-919) was cloned into pGex4t.1. Large scale GST-tagged AR-LBD was prepared and purified using a GST column. Recombinant AR-LBD was combined with [3H]mibolerone (PerkinElmer, Waltham, Mass.) in buffer A (10 mM Tris, pH 7.4, 1.5 mM disodium EDTA, 0.25 M sucrose, 10 mM sodium molybdate, 1 mM PMSF) to determine the equilibrium dissociation constant (Kd) of [3H]mibolerone. Protein was incubated with increasing concentrations of [3H]mibolerone with and without a high concentration of unlabeled mibolerone at 4° C. for 18 h in order to determine total and non-specific binding. Non-specific binding was then subtracted from total binding to determine specific binding and non-linear regression for the ligand binding curve with one site saturation was used to determine the Kd of mibolerone.Increasing concentrations of SARDs or DHT (range: 10−12 to 10−4 M) were incubated with [3H]mibolerone and AR-LBD using the conditions described above. Following incubation, the ligand bound AR-LBD complex was isolated using BiogelHT hydroxyapatite, washed and counted in a scintillation counter after adding scintillation cocktail.
Measurement: Ki = 2225 nM (pChEMBL 5.650000095367432)
Descriptors: MW 383.29, ALogP 2.07, HBA 7, HBD 2, PSA 134.08, QED 0.6
Compound (SMILES): Cc1c(Br)cc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: IBDOGMBSQPMZKN-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of FAAH in human U937 cells using [ethanolamine-1-3H]AEA as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 435.34, ALogP 4.56, HBA 3, HBD 1, PSA 51.1, QED 0.72
Compound (SMILES): CN(C)C(=O)[C@@H]1CN(C2CCCCC2)CC[C@H]1NC(=O)c1cc(-c2ccc(F)cc2F)on1
InChIKey: WTQZMARGZPHBHA-UYAOXDASSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: In Vitro Assay: Tango CXCR7-bla U2OS cells are detached from culture dishes with 0.05% trypsin-EDTA and collected in growing medium (McCoy's 5A 90% (v/v), dialyzed FCS 10% (v/v), 0.1 mM NEAA, 25 mM HEPES (pH7.3), 1 mM sodium pyruvate, P/S 1% (v/v) 50 μg/ml Hygromycin, 100 μg/ml Geneticin, 200 μg/ml Zeocin), spinned down and resuspended in assay medium (McCoy's 5A 90% (v/v), dialyzed FCS 1% (v/v), 0.1 mM NEAA, 25 mM HEPES (pH7.3), P/S 1% (v/v)). 10′000 cells per well (in 30 μl) are seeded in a 384 well plate (black-walled, clear bottom). The plate is incubated at 37° C./5% CO2 for 24 hours. Test compounds are dissolved to 10 mM in DMSO and serially diluted in DMSO to 500× of the final concentration for dose response curves. Compounds are then diluted 1:100 in assay medium to 5× of the final concentration. 10 μl/well of diluted compounds are added to the assay plate and incubated for 15 minutes at 37° C. Thereafter CXCL12/SDF1-α is diluted in assay medium to 5× of the final concentration (its EC80 value for receptor activation) and 10 μl/well are added to the assay plate. The agonist leads to activation of the receptor and therefore to b-arrestin recruitment. Compounds acting as antagonists reduce this activation. The plate is incubated for 22 hrs at 37° C. 10 μl/well of detection reagent (LiveBLAzer-FRET BIG (CCF4-AM) substrate) is transferred to the assay plate and the plate is incubated for 2 hours at room temperature protected from light. Fluorescent counts are determined (Scan1: Ex 409/20 nm, Em 460/30 nm, Scan 2: Ex 409/20 nm, Em 530/30 nm).
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 460.53, ALogP 3.46, HBA 5, HBD 1, PSA 78.68, QED 0.74
Compound (SMILES): COc1cccc(NC(=O)CSc2nnc(-c3ccc(S(N)(=O)=O)cc3)o2)c1
InChIKey: ITPIUJSTAATYDD-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 53.1 nM (pChEMBL 7.28000020980835)
Descriptors: MW 420.47, ALogP 2.12, HBA 8, HBD 2, PSA 137.41, QED 0.55
Compound (SMILES): CC(C)n1ncc2c1C(=O)CC1(CCN(C(=O)c3cc(-c4ccc(C(=O)O)cc4)nc(N(C)C)c3)CC1)C2
InChIKey: NMUDXSTWPJFVCN-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition of recombinant human ACC1 using acetyl coA as substrate incubated for 1 hr by transcreener fluorescence polarization assay
Measurement: IC50 = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 515.61, ALogP 4.34, HBA 7, HBD 1, PSA 108.63, QED 0.54
Compound (SMILES): CC(C)Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NCc3ccc(C(=O)NO)cc3)cc12
InChIKey: OOGDOIHBGKKMQF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 1 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 31.3 nM (pChEMBL 7.5)
Descriptors: MW 532.6, ALogP 3.6, HBA 7, HBD 5, PSA 145.68, QED 0.17
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CCN2CCN(c3ccc(C(F)(F)F)cc3)CC2)cc1
InChIKey: MHPFLUVTUFEMGN-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 by stopped-flow CO2 hydration assay
Measurement: Ki = 61.3 nM (pChEMBL 7.210000038146973)
Descriptors: MW 470.52, ALogP 2.18, HBA 5, HBD 2, PSA 95.74, QED 0.65
Compound (SMILES): c1cncc(-c2cc3c(-c4cc5cccnc5[nH]4)n[nH]c3cn2)c1
InChIKey: NDWPEOZTOKJNQO-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 5488 nM (pChEMBL 5.260000228881836)
Descriptors: MW 312.34, ALogP 3.56, HBA 4, HBD 2, PSA 83.14, QED 0.52
Compound (SMILES): Cc1cc(F)cc(C)c1Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NCc3ccc(C(=O)Nc4ccccc4N)cc3)cc12
InChIKey: OQSJECKEYLFTOJ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 36.6 nM (pChEMBL 7.440000057220459)
Descriptors: MW 687.77, ALogP 7.07, HBA 7, HBD 5, PSA 151.47, QED 0.1
Compound (SMILES): C=CC(=O)NCCOCCNC(=O)CCN1CCC(c2cc(OC(C)C)c(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)cc2C)CC1
InChIKey: XGZORHKVFKUMAV-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of INSR (unknown origin)
Measurement: IC50 = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 770.4, ALogP 5.9, HBA 11, HBD 4, PSA 163.88, QED 0.08
Compound (SMILES): CO[C@@]12CC[C@H](N[C@@H](Cc3ccc(O)cc3)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: KEGUIZOWBNACNM-KTUZKFFASA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]U69,593 from kappa opioid receptor in guinea-pig brain membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 39.5 nM (pChEMBL 7.400000095367432)
Descriptors: MW 480.56, ALogP 2.19, HBA 7, HBD 4, PSA 111.49, QED 0.5
Compound (SMILES): O=C(/C=C/c1ccc(F)cc1)Nc1ccc2oc(=O)ccc2c1
InChIKey: MJJVZWVJDKKFDF-YCRREMRBSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 40.9 nM (pChEMBL 7.389999866485596)
Descriptors: MW 309.3, ALogP 3.58, HBA 3, HBD 1, PSA 59.31, QED 0.59
Compound (SMILES): CCOc1ccc2cc(-c3nn(CC(C)(C)CO)c(N)c3C(N)=O)ccc2c1
InChIKey: ACIRYYGVYGOFQP-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of SRC (unknown origin)
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 382.46, ALogP 2.8, HBA 6, HBD 3, PSA 116.39, QED 0.58
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)C(=O)N1CC[C@H](c2ccnc3ccc(F)cc23)[C@@H](O)C1
InChIKey: GZSMNWZYUMDTHO-XLIONFOSSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 427.86, ALogP 3.34, HBA 4, HBD 2, PSA 82.53, QED 0.61
Compound (SMILES): Br.N=C(N)SCc1ccc(CN2C(=O)C(=O)c3cccc(F)c32)cc1
InChIKey: YVFMEVAVUHOGRO-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, dimeric NADP-preferring (SINGLE PROTEIN), Homo sapiens
UniProt: P30838
Assay: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate
Measurement: IC50 = 241 nM (pChEMBL 6.619999885559082)
Descriptors: MW 343.38, ALogP 2.68, HBA 4, HBD 2, PSA 87.25, QED 0.51
Compound (SMILES): CCC(=O)Nc1cncc(-c2ccc3[nH]nc(-c4cc5c(-c6cc(F)cc(CNS(C)(=O)=O)c6)cncc5[nH]4)c3c2)c1
InChIKey: MBGMUEGKTJKVLY-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 216 nM (pChEMBL 6.670000076293945)
Descriptors: MW 583.65, ALogP 5.37, HBA 6, HBD 4, PSA 145.52, QED 0.19
Compound (SMILES): Cn1cc(-c2cnc3[nH]nc(-c4nc5c(-c6cccc(F)c6)nccc5[nH]4)c3c2)cn1
InChIKey: PEWFRAFAZFATDK-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 410.42, ALogP 4.1, HBA 6, HBD 2, PSA 100.96, QED 0.46
Compound (SMILES): Nc1cc(Cc2ccccc2)c2nn[nH]c2n1
InChIKey: SGFFXIGIHATQNC-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: Inhibition of recombinant human MPO incubated for 10 mins by amplex red dye based assay
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 225.25, ALogP 1.53, HBA 4, HBD 2, PSA 80.48, QED 0.69
Compound (SMILES): Cn1ccc(-c2cn3nccc3c(-c3cnn([C@]4(CC#N)C[C@@H](C#N)C4)c3)n2)n1
InChIKey: KOOMDXSXMHFXMV-OYOVHJISSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 catalytic domain (809 to 1153+9 residues) expressed in baculovirus expression system using FITC-KGGEEEEYFELVKK as substrate in presence of ATP at Km by microfluidic assay
Measurement: IC50 = 467 nM (pChEMBL 6.329999923706055)
Descriptors: MW 383.42, ALogP 2.54, HBA 9, HBD 0, PSA 113.41, QED 0.53
Compound (SMILES): CCn1c(-c2cnc(C)nc2)nc2c(-c3ccc4c(c3)[C@@]3(CCCN3C(=O)C3CC3)C(=O)N4C)ncnc21
InChIKey: ZRNOMAUJWZTHTM-NDEPHWFRSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human whole blood assessed as reduction in anti-CD79b antibody-induced CD69 expression preincubated for 60 mins followed by anti-CD79b antibody stimulation for 3 hrs by FACS analysis
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 508.59, ALogP 3.48, HBA 8, HBD 0, PSA 110, QED 0.42
Compound (SMILES): Cc1cc(C(=O)O)nc(N2CCCC(COc3ccccc3C(F)(F)F)C2)n1
InChIKey: PXAAMJAKNDKIDA-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: Displacement of FITC-diclofenac from human plasma derived TTR measured after overnight incubation by fluorescence polarization assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 395.38, ALogP 3.8, HBA 5, HBD 1, PSA 75.55, QED 0.83
Compound (SMILES): c1ccc(CCCN2CCCc3ccccc3CC2)cc1
InChIKey: GDRMBJLFSZXVHD-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma 2 receptor in rat liver membranes incubated for 120 mins by scintillation counting method
Measurement: Ki = 178 nM (pChEMBL 6.75)
Descriptors: MW 279.43, ALogP 4.11, HBA 1, HBD 0, PSA 3.24, QED 0.81
Compound (SMILES): CC1(CN)CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: ZAMNYDQBNJFTSZ-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: SHP2 Allosteric Inhibition Assay: More specifically, the phosphatase reactions were performed at room temperature in 384-well black polystyrene plate, flat bottom, low flange, non-binding surface (Corning, Cat#3575) using a final reaction volume of 25 μL and the following assay buffer conditions: 60 mM HEPES, pH 7.2, 75 mM NaCl, 75 mM KCl, 1 mM EDTA, 0.05% P-20, 5 mM DTT. The inhibition of SHP2 by compounds of the invention (concentrations varying from 0.003-100 μM) was monitored using an assay in which 0.5 nM of SHP2 was incubated with of 0.5 μM of peptide IRS1_pY1172(dPEG8)pY1222 (sequence: H2N-LN(pY)IDLDLV(dPEG8)LST(pY)ASINFQK-amide) (SEQ ID NO:1). After 30-60 minutes incubation at 25° C., the surrogate substrate DiFMUP (Invitrogen, cat# D6567) was added to the reaction and incubated at 25° C. for 30 minutes. The reaction was then quenched by the addition of 5 μl of a 160 μM solution of bpV(Phen) (Enzo Life Sciences cat# ALX-270-204). The fluorescence signal was monitored using a microplate reader (Envision, Perki-Elmer) using excitation and emission wavelengths of 340 nm and 450 nm, respectively. The inhibitor dose response curves were analyzed using normalized IC50 regression curve fitting with control based normalization.
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 366.3, ALogP 3.6, HBA 5, HBD 2, PSA 81.06, QED 0.87
Compound (SMILES): CN1CCC(CNC(=O)c2cc(-n3cc(NC(=O)Nc4ccccc4Cl)cn3)cs2)CC1
InChIKey: ZCXZADLHKFAMEG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3alpha1 (unknown origin) using ATF2 as substrate after 22 mins in presence of ATP by HTRF assay
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 473, ALogP 4.3, HBA 6, HBD 3, PSA 91.29, QED 0.5
Compound (SMILES): COc1ccn2c(=O)n(CC(=O)N[C@@H](C)c3c(C)cc(C)cc3C)nc2c1
InChIKey: UIAXTCQOAJVCSA-HNNXBMFYSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 368.44, ALogP 2.31, HBA 6, HBD 1, PSA 77.63, QED 0.75
Compound (SMILES): C[C@H]1[C@H](O)CN1c1nc(N2C[C@@H]3[C@@H](CC(=O)O)[C@@H]3C2)cc(C(F)(F)F)c1C#N
InChIKey: BMYWDILFDVCFJX-GMEDAVPMSA-N
Target: Ketohexokinase (SINGLE PROTEIN), Homo sapiens
UniProt: P50053
Assay: KHK Assay A: A 384-well format on a Corning 3653 assay plate is used, and monitored by UV-vis spectroscopy in continuous mode at rt. Compounds were prepared in DMSO as 4 mM stocks, diluted using an 11-point half-log scheme on a Biomek FX (Beckman Coulter), and incubated at rt for 30 minutes with the reaction mixture containing 50 mM HEPES, pH 7.4, 140 mM KCl, 3.5 mM MgCl2, 0.8 mM fructose, 2 mM TCEP, 0.8 mM PEP, 0.7 mM NADH, 0.01% Triton X-100, 30 U/mL pyruvate kinase-lactate dehydrogenase, and 10 nM purified KHK-C. The compound concentration in each well ranged from 1 nM to 100 μM. The reaction was initiated with the addition of 0.2 mM ATP. The absorbance was measured for 30 minutes on a SpectraMax reader (Molecular Devices) after ATP was added. The concentrations provided are based on the final mixture volume of 40 μL (referred to as the final concentration).Controls: N8-(cyclopropylmethyl)-N4-(2-(methylthio)phenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine at 2 μM final concentration was used as high percent effect (HPE) control, and 2.5% DMSO which was present in all reaction wells was used as zero percent effect (ZPE) control. Reaction rates were obtained for 300-1800 seconds time window in units of 1000*AU/min (absorbance unit per minute), and average values for ZPE and HPE controls from 16 wells each were calculated, AveZPE and AveHPE, respectively.Percent inhibition (% inhibition) was calculated for each well using this equation:100 - 100 × ( Compound ⁢ ⁢ absorbance ⁢ ⁢ rate ⁢ ⁢ value - Ave HPE ) ( Ave ZPE - Ave HPE )The % inhibition was then plotted against the log of compound concentration using GraphPad Prism, and the data was fit to the equation log [compound] vs. response variable slope using nonlinear regression analysis to give IC50 values. For each compound tested, the IC50 provided is the average based on at least two separate assays conducted on separate days.
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 396.37, ALogP 1.7, HBA 6, HBD 2, PSA 100.69, QED 0.8
Compound (SMILES): N#Cc1ccc(Nc2cc(Nc3cccc(O)c3)nc(-c3ccccc3)n2)cc1
InChIKey: VMGPVNFOVJEIAF-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of ABCC1 (unknown origin) expressed in human NCI-H69AR cells assessed as reduction in calcein AM efflux preincubated for 30 mins followed by calcein AM addition and measured at 60 secs interval for 1 hr by fluorescence assay
Measurement: IC50 = 4080 nM (pChEMBL 5.389999866485596)
Descriptors: MW 379.42, ALogP 5.21, HBA 6, HBD 3, PSA 93.86, QED 0.44
Compound (SMILES): COc1ccc(/C=N/c2c(C#N)c(-c3ccc(Cl)cc3)cn2-c2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: MRJABSSYPXPUJQ-WKULSOCRSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 2707.7 nM (pChEMBL 5.570000171661377)
Descriptors: MW 490.97, ALogP 5.08, HBA 6, HBD 1, PSA 110.47, QED 0.38