lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)c1ccc(-n2cc(C3(O)CCCC3)nn2)cc1
InChIKey: BQYVYOXOURDCJA-UHFFFAOYSA-N
Target: ORF 73 (SINGLE PROTEIN), Human herpesvirus 8
UniProt: O40947
Assay: Inhibition of fluorescent labelled LBS1 DNA binding to human herpesvirus 8 C-terminal His-tagged LANA oligomerization deficient mutant DBD (1008 to 1146 residues) expressed in Escherichia coli BL21 (DE3) preincubated for 60 mins followed by fluorescent labelled LBS2 addition and measured after 90 mins by fluorescence polarization assay
Measurement: IC50 = 104000 nM (pChEMBL 3.9800000190734863)
Descriptors: MW 273.29, ALogP 1.73, HBA 5, HBD 2, PSA 88.24, QED 0.89
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4c4ccc(NCC(N)=O)cc4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: FDXVKEVTTKXCLD-ZZVPPEEFSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from rat DOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting
Measurement: Ki = 57.3 nM (pChEMBL 7.239999771118164)
Descriptors: MW 529.68, ALogP 3.98, HBA 6, HBD 2, PSA 86.05, QED 0.54
Compound (SMILES): Nc1ccccc1S(=O)(=O)[N-][N+](=O)[O-].[Ag+]
InChIKey: HCZODDJYFZZYSE-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 60900 nM (pChEMBL 4.210000038146973)
Descriptors: MW 216.2, ALogP 0.52, HBA 5, HBD 1, PSA 117.4, QED 0.45
Compound (SMILES): Cc1cccc(NC(=O)CN2CCC(c3ccc(Cl)cc3)CC2)c1
InChIKey: MGAAMGRSXKBQAO-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3 receptor expressed in HEK293 cell membranes measured after 60 mins by scintillation counting method
Measurement: Ki = 26320 nM (pChEMBL 4.579999923706055)
Descriptors: MW 342.87, ALogP 4.47, HBA 2, HBD 1, PSA 32.34, QED 0.89
Compound (SMILES): O=C1c2cc(F)ccc2-n2c1nc1ccc(CN3CCNCC3)cc1c2=O
InChIKey: QAPKRPGAKVBFCQ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6ZQW0
Assay: Inhibition of C-terminal His6-tagged human IDO2 (14 to 420 residues) expressed in Escherichia coli BL21 (DE3) assessed as reduction in conversion of L-tryptophan to N-formyl kynurenine using L-tryptophan as substrate after 30 mins by methylene blue dye based microplate reader analysis
Measurement: IC50 = 31450 nM (pChEMBL 4.5)
Descriptors: MW 364.38, ALogP 1.47, HBA 6, HBD 1, PSA 67.23, QED 0.58
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCOCCOCCNC(=O)OC(C)(C)C)c1nnc(C)n1-2
InChIKey: LMYKZDUQLVXDIX-QHCPKHFHSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Inhibition of BRD3 (unknown origin) by TR-FRET assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 631.2, ALogP 4.86, HBA 10, HBD 2, PSA 128.96, QED 0.27
Compound (SMILES): CC(C)(C)c1ccc(C[C@]2(O)CC[C@H]3[C@@H]4CC=C5C[C@@H](OS(N)(=O)=O)CC[C@]5(C)[C@H]4CC[C@@]32C)cc1
InChIKey: FHHHJWXRFGAVKG-RORXSCKRSA-N
Target: Steryl-sulfatase (SINGLE PROTEIN), Homo sapiens
UniProt: P08842
Assay: Inhibition of sulfatase (unknown origin) expressed in HEK293 cells using [3H]DHEAS as substrate after 2 hrs by liquid scintillation counting method
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 515.76, ALogP 5.81, HBA 4, HBD 2, PSA 89.62, QED 0.5
Compound (SMILES): CN1C(=O)c2cccc3c(NS(=O)(=O)c4ccccc4Cl)ccc1c23
InChIKey: HRFYKDGKRHPODF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of tetra-acetylated histone H4 peptide (1-21) from recombinant human N-terminal His-tagged BRD4 BD2 (349 to 460 residues) expressed in Escherichia coli incubated for 30 mins followed by further incubation with tetra-acetylated histone H4 peptide (1-21) for 30 mins by Alphascreen assay
Measurement: IC50 = 6048 nM (pChEMBL 5.21999979019165)
Descriptors: MW 372.83, ALogP 3.88, HBA 3, HBD 1, PSA 66.48, QED 0.76
Compound (SMILES): O=c1cc(O)c2c(=O)oc3c4ccccc4ccc3c2o1
InChIKey: NAOYAHOPOSSALQ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of LEDGF/p75-dependent full length HIV-1 integrase expressed in Escherichia coli BL21(DE3) cells preincubated for 1 hr further incubated for 90 mins with biotin-labeled donor DNA and target DNA by HTRF assay
Measurement: IC50 = 7500 nM (pChEMBL 5.119999885559082)
Descriptors: MW 280.24, ALogP 2.76, HBA 5, HBD 1, PSA 80.65, QED 0.4
Compound (SMILES): C[C@H]1NC(=O)c2cc(-c3cccc4c(=O)n(C(C)(C)C)c(NC(C)(C)C)nc34)[nH]c21
InChIKey: NICUEZQIMBHMRX-GFCCVEGCSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of full length recombinant PIM2 (unknown origin) assessed as reduction in BAD phosphorylation at Ser112 residues preincubated for 30 mins followed by biotinylated BAD addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 0.83 nM (pChEMBL 9.079999923706055)
Descriptors: MW 407.52, ALogP 4.16, HBA 5, HBD 3, PSA 91.81, QED 0.59
Compound (SMILES): O=C1CN(c2cc3nccnc3c(NC[C@H]3CCCNC3)n2)CCN1
InChIKey: WVLAYLIGJMFARP-LBPRGKRZSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of N-terminal-6His-tagged full length human Aurora B expressed in baculovirus using 5FAM-PKA-tide as substrate after 120 mins by fluorescence polarization assay
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 341.42, ALogP 0.37, HBA 7, HBD 3, PSA 95.07, QED 0.74
Compound (SMILES): N#Cc1c(N)nc(SCc2ccncc2)c(C#N)c1-c1ccco1
InChIKey: XDDKKVMAZSJNOX-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [125I]ABMECA from human A3R expressed in CHO cell membranes measured after 120 mins by scintillation counting method
Measurement: Ki = 678 nM (pChEMBL 6.170000076293945)
Descriptors: MW 333.38, ALogP 3.35, HBA 7, HBD 1, PSA 112.52, QED 0.73
Compound (SMILES): Cc1nc(N2CCOCC2)ccc1Nc1nc(NC(C)(C)CO)c2c(C#N)c[nH]c2n1
InChIKey: JCVATYGNKPJBLI-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of MPS1 (510 to 857 residues) catalytic domain (unknown origin) expressed in Escherichia coli after 15 mins by mass-spectrometry analysis
Measurement: Ki < 0.5 nM (pChEMBL 9.300999641418457)
Descriptors: MW 422.49, ALogP 2.3, HBA 9, HBD 4, PSA 135.01, QED 0.47
Compound (SMILES): COc1ccc(-c2noc(N)c2-c2ccc(OC)cc2)cc1
InChIKey: DIHASZCPXYPHRC-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 using arachidonic acid as substrate by colorimetric assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 296.33, ALogP 3.61, HBA 5, HBD 1, PSA 70.51, QED 0.8
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(C)=O)C(C)C)C(C)O)[C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C(C)C)[C@@H](C)CC)C(C)C
InChIKey: DSTIFCWWLQRNDR-VQDYIRONSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 2510 nM (pChEMBL 5.599999904632568)
Descriptors: MW 3717.46
Compound (SMILES): CS(=O)(=O)c1ccc(-c2cncc(/C=C3\SC(=N)NC3=O)c2)cc1
InChIKey: JITAYSQVLSDQMN-AUWJEWJLSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of GST-tagged recombinant PI5P4Kalpha (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 359.43, ALogP 2.29, HBA 6, HBD 2, PSA 99.98, QED 0.82
Compound (SMILES): CCCNS(=O)(=O)Nc1ncnc(OCCOc2ncc(SC)cn2)c1-c1ccc(Cl)cc1
InChIKey: QRKZNZMLWQPCPE-UHFFFAOYSA-N
Target: Endothelin receptor type B (SINGLE PROTEIN), Homo sapiens
UniProt: P24530
Assay: Displacement of [125I]-ET-1 from human ETB receptor expressed in CHO cell membranes after 2 hrs by scintillation counting
Measurement: IC50 = 686 nM (pChEMBL 6.159999847412109)
Descriptors: MW 511.03, ALogP 3.42, HBA 9, HBD 2, PSA 128.22, QED 0.28
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N[C@H]2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)nc1
InChIKey: WFWFIAFTMSUDNO-CHUTXNTCSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Competitive irreversible inhibition of CDK7/cyclinH/MAT1 (unknown origin) using 5-FAM YSPTSPSYSPTSPSYSPTSPSKKKK as substrate in presence of Km ATP
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 573.1, ALogP 4.88, HBA 7, HBD 4, PSA 127.93, QED 0.21
Compound (SMILES): CC1CCc2cc(F)cc3c(O)c(C(=O)NCc4cccnc4N(C)C)c(=O)n1c23
InChIKey: YNKJJGDFHRUXAQ-UHFFFAOYSA-N
Target: Toll-like receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60603
Assay: Agonist activity at human TLR2 expressed in HEK-Blue cells harboring NFkB promoter-driven secreted alkaline phosphatase assessed as induction of NFkB after 12 hrs by spectrophotometric assay
Measurement: EC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 410.45, ALogP 2.74, HBA 6, HBD 2, PSA 87.46, QED 0.69
Compound (SMILES): O=C(NCCN1CCC2(CC1)C(=O)NC[C@@H]2c1ccc(F)cc1)c1cc2ccccc2[nH]1
InChIKey: MLJJFIFPBSIXMF-HXUWFJFHSA-N
Target: Phospholipase D1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13393
Assay: Inhibition of PLD1 in human Calu1 cells
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 434.52, ALogP 3.03, HBA 3, HBD 3, PSA 77.23, QED 0.58
Compound (SMILES): CS(=O)(=O)CCC(=O)NCCSc1nonc1/C(=N/O)Nc1ccc(F)c(Br)c1
InChIKey: HRMPMJHJLZFJMX-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in interferon-gamma-induced human SKOV3 cells assessed as N-formylkynurenine formation using L-tryptophan as substrate measured after 24 hrs by fluorescence assay
Measurement: IC50 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 510.37, ALogP 1.86, HBA 9, HBD 3, PSA 146.78, QED 0.11
Compound (SMILES): CCc1ccc(OCCN2CCN(C(=O)c3ccc(OC)cc3)CC2)cc1
InChIKey: UGQHLSRGZUTZMG-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2R expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 120 mins by beta-galactosidase based PathHunter assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 368.48, ALogP 3.09, HBA 4, HBD 0, PSA 42.01, QED 0.75
Compound (SMILES): C=CC(=O)Nc1cccc(-c2c(N)ncnc2Nc2ccc(Oc3ccccc3)cc2)c1
InChIKey: YZBXYPYYWUFAEL-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human EGFR (696 to end aminoacids) expressed in baculovirus infected Sf21 cells
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 423.48, ALogP 5.39, HBA 6, HBD 3, PSA 102.16, QED 0.34
Compound (SMILES): CC(C)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CSCCCC(=O)N[C@@H](Cc2ccc(Cl)cc2)C(=O)N[C@@H](Cc2cccs2)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N1
InChIKey: SBGJNYGRUDHZFZ-PFAGHSOOSA-N
Target: Vasopressin V1b receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47901
Assay: Agonist activity at recombinant human V1B receptor expressed in HEK293 cells measured after 5 hrs by luciferase reporter gene assay
Measurement: EC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 1031.7
Compound (SMILES): CCCCN(C)C1CCN(c2ccc(Nc3ncc(C)c(-c4cnn(C(C)C)c4)n3)cc2F)CC1
InChIKey: RCZNPCWYCXMLFZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 (808 to end residues) using KTFCGTPEYLAP as substrate after 40 mins in presence of [gamma33P]-ATP by scintillation counting based radiometric assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 479.65, ALogP 5.81, HBA 7, HBD 1, PSA 62.11, QED 0.42
Compound (SMILES): O=C1/C(=C/c2cc(OC(F)(F)F)c(O)cc2Br)Sc2ncccc21
InChIKey: FCASBCCFWWZUTR-XGICHPGQSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of CGAS in human THP1 cells transfected with interferon stimulatory DNA and measured after 16 hrs by Gaussia luciferase reporter gene assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 418.19, ALogP 4.78, HBA 5, HBD 1, PSA 59.42, QED 0.71
Compound (SMILES): Cc1ccc(-c2cc3nccnc3c(NCCCCN)n2)cc1
InChIKey: FYJFZOONLWHKMF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK in human Ramos cells assessed as suppression of anti-IgM induced Erk1/2 phosphorylation preincubated for 30 mins followed by anti-IgM addition measured after 7 mins by electrochemiluminescence analysis
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 307.4, ALogP 3.15, HBA 5, HBD 2, PSA 76.72, QED 0.68
Compound (SMILES): Cc1noc(C)c1CSCC(=O)N1CCN(c2ccccc2)CC1
InChIKey: XYGKAGVCDJECAH-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 345.47, ALogP 2.87, HBA 5, HBD 0, PSA 49.58, QED 0.83
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)NC(=O)NCCCCc1cn(CCCNC(=O)CCCCCN2/C(=C/C=C/C=C/C3=[N+](C)c4ccc5c(S(=O)(=O)[O-])cc(S(=O)(=O)O)cc5c4C3(C)C)C(C)(C)c3c2ccc2c(S(=O)(=O)O)cc(S(=O)(=O)O)cc32)nn1)C(C)(C)C)C(=O)O
InChIKey: RDKANGIHVPYEGN-ZFXFEHJRSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [3H]UR-MK300 from human NTS1R expressed in human HT-29 cells incubated for 2 hrs by scintillation counting method
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 1925.31
Compound (SMILES): COP(C)(=O)NCCCCNc1nonc1/C(=N/O)Nc1ccc(F)c(Br)c1
InChIKey: VPZIQYMEUIFNFK-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant N-terminal His-tagged human IDO1 expressed in Escherichia coli assessed as reduction in N-formylkynurenine formation using L-tryptophan as substrate
Measurement: IC50 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 479.25, ALogP 3.47, HBA 8, HBD 4, PSA 133.9, QED 0.1
Compound (SMILES): Nc1ncnc2c1c(Sc1cccc(Cl)c1)nn2[C@H]1C[C@H](O)[C@H](COS(N)(=O)=O)O1
InChIKey: OICGDVPCZSVSCO-SDDRHHMPSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 472.94, ALogP 1.08, HBA 11, HBD 3, PSA 168.47, QED 0.47
Compound (SMILES): C[C@H]1CO[C@H](c2ccc(N)nc2)CN1C/C=C/COc1ccc2c(c1)NC(=O)CC2
InChIKey: UJSKIIMXTSGSEQ-TZFUKMIJSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-(R)-(+)-7-OH-DPAT from recombinant human D3 receptor expressed in HEK293 cell membranes measured after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 73000 nM (pChEMBL 4.139999866485596)
Descriptors: MW 408.5, ALogP 2.95, HBA 6, HBD 2, PSA 89.71, QED 0.71
Compound (SMILES): CC(=O)N[C@@H](CC(C)C)CN(CC(=O)N[C@@H](Cc1ccccc1)CN(CC(=O)N[C@@H](CCC(=O)O)CN(CC(=O)N[C@@H](Cc1c[nH]c2ccccc12)CN(CC(=O)N[C@@H](CCCCN)CN(CC(=O)N[C@@H](CC(C)C)CN(CC(=O)N[C@@H](C)CN(CC(N)=O)S(C)(=O)=O)S(=O)(=O)CC(C)C)S(C)(=O)=O)S(C)(=O)=O)S(=O)(=O)c1ccc(Cl)cc1)S(C)(=O)=O)S(C)(=O)=O
InChIKey: PQXZUIONIKLWJT-JFPIBWRESA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Binding affinity to human MDM2 expressed in Escherichia coli expression system by using (FITC)-labeled p53 peptide based fluorescence polarization competitive assay
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 1933.87
Compound (SMILES): COc1cc2c3c(c1)-c1c(cccc1OCc1ccc(F)cc1)C[C@H]3N(C)CC2.Cl
InChIKey: LIJXQBITSGCQED-VZYDHVRKSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]LSD from 5HT2B receptor (unknown origin) expressed in HEK293 cell membranes
Measurement: Ki = 2681 nM (pChEMBL 5.570000171661377)
Descriptors: MW 389.47, ALogP 5.17, HBA 3, HBD 0, PSA 21.7, QED 0.61
Compound (SMILES): O=C(CCCN1CCC(O)(c2ccc(C(F)(F)F)cc2)CC1)c1ccc(F)cc1
InChIKey: FUGGMNXTBZFFDM-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of PPHT-red from SNAP-tagged human D2LR expressed in CHOK1 cell membranes by TR-FRET assay
Measurement: Ki = 0.3236 nM (pChEMBL 9.489999771118164)
Descriptors: MW 409.42, ALogP 4.79, HBA 3, HBD 1, PSA 40.54, QED 0.55
Compound (SMILES): Cc1cc(C)cc(Oc2ccc(CNC(=O)[C@H](C)N)cc2C)c1.Cl
InChIKey: OQGSBQJSJRLNQH-RSAXXLAASA-N
Target: Protein arginine N-methyltransferase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA8
Assay: Inhibition of PRMT6 (unknown origin)
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 312.41, ALogP 3.37, HBA 3, HBD 2, PSA 64.35, QED 0.89
Compound (SMILES): O=C(CCc1csc(/C=C/c2ccc(F)cc2)n1)NO
InChIKey: HZZSLNIZLYHEBV-FPYGCLRLSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human recombinant HDAC6 using fluorogenic HDAC substrate 3 pre-incubated for 30 mins followed by HDAC developer addition and measured after 15 mins by fluorogenic assay
Measurement: IC50 = 42.98 nM (pChEMBL 7.369999885559082)
Descriptors: MW 292.33, ALogP 2.89, HBA 4, HBD 2, PSA 62.22, QED 0.66
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2c(-c3c(Cl)cccc3C(F)(F)F)noc2-c2ccccc2)cc1F
InChIKey: WDXZPHIWIHOUMB-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Inverse agonist activity at His6-tagged PPARgamma LBD (unknown origin) assessed as inhibition of rosiglitazone-induced N-terminal biotinylated co-activator SRC1 box2 peptide recruitment measured after 30 mins by TR-FRET assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 504.82, ALogP 6.77, HBA 4, HBD 2, PSA 92.43, QED 0.29
Compound (SMILES): CCCCCCCCCCC/C(O)=C1/C(=O)[C@H](Cc2ccccc2)N(C(=O)OC(C)(C)C)C1=O
InChIKey: ARGQFVTUBUBLMT-KXZZPGAFSA-N
Target: Kallikrein-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P49862
Assay: Inhibition of human KLK7 assessed as reduction in enzyme activity
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 471.64, ALogP 6.68, HBA 5, HBD 1, PSA 83.91, QED 0.16
Compound (SMILES): O=S(=O)(c1ccccc1)c1ccc(N2CC(CN3CCC(C4(C5CCCC5)NCCc5ccccc54)CC3)C2)cc1
InChIKey: ISZGYKMIFCDSET-UHFFFAOYSA-N
Target: Menin (SINGLE PROTEIN), Homo sapiens
UniProt: O00255
Assay: Inhibition of FAM-probe binding to Menin (unknown origin) after 60 mins by fluorescence polarization competitive binding assay
Measurement: Ki = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 569.82, ALogP 5.9, HBA 5, HBD 1, PSA 52.65, QED 0.38
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2cncc(/C=C3\SC(=N)NC3=O)c2)cc1
InChIKey: AGHDPPGOJJYURV-AUWJEWJLSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of GST-tagged recombinant PI5P4Kalpha (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 374.45, ALogP 2.26, HBA 6, HBD 3, PSA 112.01, QED 0.71
Compound (SMILES): Cc1n[nH]cc1-c1cc2nc(C34CC(CN3)C4)[nH]c(=O)c2s1.Cl.Cl
InChIKey: MOGPGPGVPDQCHY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of N-terminal GST-tagged full-length human CDK2 (1 to 298 residues)/Cyclin E (1 to 410 residues) expressed in baculovirus expression system using histone H1 as susbtrate after 90 mins by Kinase-Glo luminescence assay
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 313.39, ALogP 1.89, HBA 5, HBD 3, PSA 86.46, QED 0.67
Compound (SMILES): Cc1cc(Cc2ccc(F)cc2)c(=O)n(C(C)C(=O)Nc2ccc(Br)cc2)n1
InChIKey: XLWYQIBXRHNRRJ-UHFFFAOYSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Biased agonist activity at human FPR1 expressed in FlpIn-CHO cells assessed as intracellular calcium mobilization by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 444.3, ALogP 4.24, HBA 4, HBD 1, PSA 63.99, QED 0.64
Compound (SMILES): C[C@H]1CCN(S(=O)(=O)c2cc(NC(=O)Cn3c(=O)oc4ccccc43)ccc2Br)C1
InChIKey: DZEUJSRMZCAZKK-ZDUSSCGKSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of Alexa Fluor 647-labeled GSK tracer from FLAG-6His-Tev-fused CECR2 (424 to 543 residue) (unknown origin) measured after 15 mins by TR-FRET assay
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 494.37, ALogP 3.03, HBA 6, HBD 1, PSA 101.62, QED 0.59
Compound (SMILES): COc1ccc(Cn2cc(CCC(=O)Nc3nnc(CCCCc4nnc(NC(=O)Cc5ccccc5)s4)s3)nn2)cc1
InChIKey: UACNATZBNSLFEM-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of human GLS1 expressed in Escherichia coli strain BL21 (DE3)pLysS pre-incubated for 10 mins before glutamine addition and measured after 60 mins by bovine liver glutamate dehydrogenase based coupled enzyme assay
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 617.76, ALogP 4.36, HBA 12, HBD 2, PSA 149.7, QED 0.16
Compound (SMILES): COCCS(=O)(=O)Nc1cc(-c2cc3c(c(OC[C@H]4CN(C5CCC5)CCO4)c2)COC3)cnc1OC
InChIKey: FAFZLPBLAIRXLI-JOCHJYFZSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged p110alpha/human recombinant full-length untagged p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of biotin-PIP3 by HTRF assay
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 533.65, ALogP 2.81, HBA 9, HBD 1, PSA 108.45, QED 0.47
Compound (SMILES): CNCC(O)CN1CCc2c(Br)cccc2C1
InChIKey: RHXXQRCZGDBNIH-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99873
Assay: Inhibition of PRMT1 (unknown origin) preincubated for 15 mins followed by substrate addition and measured after 60 mins by AlphaLisa assay
Measurement: IC50 = 58800 nM (pChEMBL 4.230000019073486)
Descriptors: MW 299.21, ALogP 1.39, HBA 3, HBD 2, PSA 35.5, QED 0.88
Compound (SMILES): COc1cc2sc(C(=O)[C@H]3C[C@H]3C(=O)O)cc2c(F)c1OC
InChIKey: IBUSCTZDUNAKRN-NKWVEPMBSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: STING Biochemical [3H]cGAMP Competition Assay: The individual compounds described in the Examples herein are defined as STING agonists by (i) binding to the STING protein as evidenced by a reduction in binding of tritiated cGAMP ligand to the STING protein by at least 20% at 20 uM (concentration of compound being tested) in a STING Biochemical 13H1-cGAMP Competition Assay and (ii) demonstrating interferon production with a 6% or greater induction of IFN-β secretion at 30 uM in the THP1 cell assay (where induction caused by cGAMP at 30 uM was set at 100%).The ability of compounds to bind STING is quantified by the ability to compete with tritiated cGAMP ligand for human STING receptor membrane using a radioactive filter-binding assay. The binding assay employs STING receptor obtained from Hi-Five cell membranes overexpressing full-length HAQ STING prepared in-house and tritiated cGAMP ligand also purified in-house.
Measurement: EC50 = 599 nM (pChEMBL 6.21999979019165)
Descriptors: MW 324.33, ALogP 2.96, HBA 5, HBD 1, PSA 72.83, QED 0.86
Compound (SMILES): Cc1cccc2oc(=O)c3c(c12)CCN(C(=O)c1ccc(C(=O)O)cc1)C3
InChIKey: CEKSFWSPRIFGTB-UHFFFAOYSA-N
Target: C-1-tetrahydrofolate synthase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: P11586
Assay: Inhibition of recombinant MTHFD1 (unknown origin) using THF as substrate incubated for 30 mins in presence of NAD
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 363.37, ALogP 3, HBA 4, HBD 1, PSA 87.82, QED 0.71
Compound (SMILES): Cc1cccc(-c2cn(Cc3ccc(-c4cnn(C)c4)cc3)nn2)c1
InChIKey: UJNGCJHVITVOEU-UHFFFAOYSA-N
Target: Angiopoietin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q02763
Assay: Inhibition of Tie-2 (unknown origin) after 1 hrs by ADP-Glo luminescence assay
Measurement: IC50 = 51.44 nM (pChEMBL 7.289999961853027)
Descriptors: MW 329.41, ALogP 3.7, HBA 5, HBD 0, PSA 48.53, QED 0.57
Compound (SMILES): COc1ccccc1Cc1cc(C)nn(CC(=O)Nc2cccc(C#N)c2)c1=O
InChIKey: IXYHUKTYKQPWLA-UHFFFAOYSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Biased agonist activity at human FPR1 expressed in FlpIn-CHO cells assessed as intracellular calcium mobilization by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 388.43, ALogP 2.66, HBA 6, HBD 1, PSA 97.01, QED 0.7
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCc1cn(Cc2ccc(OC)cc2)nn1
InChIKey: IJHIBLXDVDXQDY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human N-terminal GST-tagged EGFR T790M/L858R double mutant (696 to end residues) expressed in baculovirus infected sf21 cells using poly(Glu, Tyr) 4:1 as substrate
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 559.99, ALogP 5.52, HBA 9, HBD 2, PSA 116.08, QED 0.21
Compound (SMILES): NC(=O)c1cccc(CCCN(CC[C@H](N)C(=O)O)C[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](O)[C@@H]2O)c1
InChIKey: VSETVFOQAVXGIV-NMNPZVDOSA-N
Target: Nicotinamide N-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P40261
Assay: Inhibition of full-length human N-terminal TEV cleavage site NNMT (1 to 270 residues) expressed in Escherichia coli BL21-CodonPlus(DE3)-RIPL cells using nicotinamide as substrate preincubated for 10 mins in presence of AdoMet followed by substrate addition by fluorescence based SAHH-coupled assay
Measurement: Ki = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 528.57, ALogP -1.14, HBA 12, HBD 6, PSA 228.96, QED 0.16
Compound (SMILES): COc1ncc(-c2ccc(-c3cnc4c(c3)CN(C)C4=O)s2)cc1NS(=O)(=O)c1ccccc1[N+](=O)[O-]
InChIKey: VQNVBHVDJUZZFW-UHFFFAOYSA-N
Target: Perforin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14222
Assay: Inhibition of perforin in human KHYG-1 cells pre-treated with compound for 20 mins assessed as reduction in KHYG-1 cells-mediated cell lysis of human K562 cells measured after 4 hrs by 51Cr release based gamma counting method
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 537.58, ALogP 4.18, HBA 9, HBD 1, PSA 144.63, QED 0.27
Compound (SMILES): CC1CCN(c2nc3cc(Cl)ccc3[nH]2)CC1
InChIKey: WXZXDJIMXHEXCD-UHFFFAOYSA-N
Target: Short transient receptor potential channel 5 (SINGLE PROTEIN), Mus musculus
UniProt: Q9QX29
Assay: Inhibition of mouse TRPC5 expressed in HEK293 cells co-expressing mu-opioid receptor assessed as reduction in DAMGO-induced membrane potential by FMP-2 dye based assay
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 249.74, ALogP 3.45, HBA 2, HBD 1, PSA 31.92, QED 0.84
Compound (SMILES): O=C(NCCN1CCOCC1)Nc1nc2ccc(Sc3nnc4cccnn34)cc2s1
InChIKey: NCUXYLOSWNSCIT-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of phosphorylated MET Y1230H mutant (unknown origin) pre-incubated for 30 mins before biotinylated poly(glutamate-alanine-tyrosine) peptide addition and measured after 5 mins by HTRF assay
Measurement: IC50 = 4805 nM (pChEMBL 5.320000171661377)
Descriptors: MW 456.56, ALogP 2.34, HBA 10, HBD 2, PSA 109.57, QED 0.46
Compound (SMILES): Cc1cncc(CN2CCN(c3c(C)n(Cc4c(F)cccc4C(F)(F)F)c(=O)n(C[C@H](N)c4ccccc4)c3=O)CC2)c1
InChIKey: ZGSJSAVXIPUJQV-NDEPHWFRSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Displacement of [125I]D-Trp6-LHRH from human GnRH receptor expressed in CHO-K1 cell membranes incubated for 1 hr by competitive binding assay
Measurement: IC50 = 7.18 nM (pChEMBL 8.140000343322754)
Descriptors: MW 610.66, ALogP 4.25, HBA 8, HBD 1, PSA 89.39, QED 0.3
Compound (SMILES): COc1ccccc1N1CCN(c2nc3c(c(=O)[nH]2)CC(C)CC3)CC1
InChIKey: UEQBNHNPGWISOI-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of recombinant human N-terminal TEV cleavage site-fused/FLAG-poly his-tagged TNKS2 SAM-PARP domain (613 to 1166 residues) expressed in Escherichia coli assessed as reduction in auto-PARylation preincubated for 10 mins followed by biotinylated-NAD+ addition and measured after 45 mins by ELISA
Measurement: IC50 = 3476 nM (pChEMBL 5.460000038146973)
Descriptors: MW 354.45, ALogP 2.23, HBA 5, HBD 1, PSA 61.46, QED 0.92
Compound (SMILES): CCC[C@H](O)c1c(/C=C/[C@@H](O)[C@@H](O)CCCC(=O)OC)nc(C)n1C
InChIKey: PPSSTCSZVRFORP-RNEVZHRXSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Agonist activity at ALX/FPR2 in human THP1 cells harboring NF-kB-Luc assessed as inhibition of LPS-induced NFkB signalling activation by measuring reduction in IFNgamma secretion pretreated for 30 mins followed by LPS stimulation for 24 hrs by electrochemiluminescence assay
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 354.45, ALogP 1.64, HBA 7, HBD 3, PSA 104.81, QED 0.55
Compound (SMILES): CCn1cc(Nc2nccc(-c3ccn([C@H](CO)c4ccc(Cl)c(F)c4)c(=O)c3)n2)cn1
InChIKey: AHLQZQZJOIUMQN-HXUWFJFHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin)
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 454.89, ALogP 3.64, HBA 8, HBD 2, PSA 97.86, QED 0.44
Compound (SMILES): CC(C)CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)NC(C)(C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(N)=O)C(C)(C)C)C(C)C
InChIKey: XLHMKYBQRNWGEB-GUBWNGKLSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 2444.87
Compound (SMILES): CN(C)Cc1ccc(S(=O)(=O)N2CCC(NC(=O)c3cc(C4CC4)on3)CC2)cc1
InChIKey: JDEQZHRIIJULBC-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SMYD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H7B4
Assay: Inhibition of recombinant SMYD3 (unknown origin) transfected in human HEK293 cells assessed as reduction in MEKK2 methylation incubated for 24 hrs by cellular mechanistic assay
Measurement: EC50 = 597 nM (pChEMBL 6.21999979019165)
Descriptors: MW 432.55, ALogP 2.2, HBA 6, HBD 1, PSA 95.75, QED 0.72
Compound (SMILES): CCc1sc2ncnc(N[C@H](Cc3ccccc3)C(=O)O)c2c1-c1cccc2[nH]ccc12
InChIKey: IZDAFHXFYWJQKU-LJQANCHMSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of N-terminal fluorescein labelled Puma-BH3 peptide from TEV-fused His-tagged human Mcl-1 expressed in Escherichia coliBL21(DE3) pLysS cells after 2 hrs by fluorescence polarization assay
Measurement: Ki = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 442.54, ALogP 5.51, HBA 5, HBD 3, PSA 90.9, QED 0.31
Compound (SMILES): CSc1cc2c(N[C@H](C)c3ccc(F)cc3)nc(C)nc2cn1
InChIKey: GHJGFPXHZCPXAN-SNVBAGLBSA-N
Target: SOS1-KRAS (PROTEIN COMPLEX), Homo sapiens
UniProt: P01116
Assay: Inhibition of human N-terminal GST-tagged K-RasG12C mutant/human N-terminal His-tagged SOS1 preincubated for 2 mis followed by SOS1 addition and measured after 20 mins in presence of GDP-Dy647P1 by HTRF assay
Measurement: IC50 = 901 nM (pChEMBL 6.039999961853027)
Descriptors: MW 328.42, ALogP 4.37, HBA 5, HBD 1, PSA 50.7, QED 0.72
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)N)CSSC[C@@H](C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CO)NC(=O)CCNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccc(O)cc2)NC1=O
InChIKey: HPWFIFCJPYOGNY-BWJPDRPBSA-N
Target: Ephrin type-A receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54764
Assay: Binding affinity to 6His-tagged EphA4 C204A mutant (29 to 104 residues) (unknown origin) expressed in Escherichia coli Origami 2 (DE3) by isothermal titration calorimetry
Measurement: Kd = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 1402.63
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2cc(-c3ccncc3)no2)C1
InChIKey: VSOICVQVGNRJGO-LLVKDONJSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 283.29, ALogP 1.02, HBA 6, HBD 1, PSA 95.05, QED 0.84
Compound (SMILES): Cc1cnc([C@]2(CNC(=O)c3cc4cc(C(F)(F)F)ccc4o3)NC(=O)NC2=O)n1C
InChIKey: PKTAGMTUNRVAKO-SFHVURJKSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNA0
Assay: Inhibition of human ADAMTS5 using 43-mer VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG as substrate measured after 3 hrs by AlphaScreen assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 435.36, ALogP 1.96, HBA 6, HBD 3, PSA 118.26, QED 0.54
Compound (SMILES): COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](N)CCCC[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)OC
InChIKey: ZDBKONQEXRKGLS-NPVFWKKLSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Agonist activity at GFP-tagged neuropeptide Y1R (unknown origin) expressed in HEK293T cells assessed as beta-arrestin2 recruitment measured after 60 mins by H33342 staining-based imaging method
Measurement: IC50 = 234.42 nM (pChEMBL 6.630000114440918)
Descriptors: MW 1736.06
Compound (SMILES): Nc1c(C(=O)NCc2ccc(C(=O)NCCCC3CCCCC3)cc2)cnn1-c1ccccc1
InChIKey: HXNUFFCHRIWTRZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15759
Assay: Inhibition of recombinant human His-tagged P38beta MAPK (1 to 364 residues) expressed in Escherichia coli incubated for 60 mins by [gamma-33P]ATP based scintillation counting method
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 459.59, ALogP 4.47, HBA 5, HBD 3, PSA 102.04, QED 0.41
Compound (SMILES): CC(=O)N1CCC(OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)c2nc3ccccc3s2)CC1.O=C(O)C(F)(F)F
InChIKey: WDTFWYHAYFAHRY-GUTACTQSSA-N
Target: Serine protease hepsin (SINGLE PROTEIN), Homo sapiens
UniProt: P05981
Assay: Inhibition of recombinant human C-terminal 10-His tagged hepsin (Arg45 to Leu417) expressed in mouse myeloma cells using Boc-QAR-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 573.72, ALogP 2.38, HBA 8, HBD 5, PSA 179.6, QED 0.11
Compound (SMILES): Cn1cc(NC(=O)c2cccc(-c3ccsc3)n2)c(C(N)=O)n1
InChIKey: SGPNWUYYNYULHU-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: IMAP Technology: The kinase activity of IRAK4 is determined by its ability to catalyze the phosphorylation of a fluorescent polypeptide substrate. The extent of phosphorylation is measured using IMAP technology (Molecular Devices) where the phosphorylated fluorescent substrate binds to the large M(III)-based nanoparticles which reduces the rotational speed of the substrate and thus increases its fluorescent polarization (FP).Specific compounds of the instant invention were tested in the assay described above and were found to have IC50 values of ≦20 μM against substrate.Procedure: A 20 μl reaction mixture contains 10 mM TriHCl, pH 7.2, 0.5 nM GST tagged IRAK4 (SignalChem), 100 nM fluorescent peptide substrate (RP7030, Molecular Devices), 100 μM ATP, 1 mM DTT, 1 mM MgCl2, and 0.01% Tween 20. The reaction is initiated by the addition of ATP. After incubation for 30 minutes at 25° C., 60 μl of Progressive IMAP Reagent (Molecular Devices) is added to stop the reaction. Change in RP7030's FP is determined by a FP reader (Analyst HT, LJL BioSystems).
Measurement: IC50 = 362 nM (pChEMBL 6.440000057220459)
Descriptors: MW 327.37, ALogP 1.89, HBA 6, HBD 2, PSA 102.9, QED 0.76
Compound (SMILES): COC1O[C@]2(CC[C@@H](NCc3ccccc3)CC2)c2ccccc21
InChIKey: NCCWUSOQZYQVLQ-WQQJRXGJSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-di-o-tolylguanidine from sigma2 receptor in rat liver membranes incubated for 120 mins in the presence of sigma1 receptor ligand (+)-pentazocine by scintillation counting method
Measurement: Ki = 751 nM (pChEMBL 6.119999885559082)
Descriptors: MW 323.44, ALogP 4.29, HBA 3, HBD 1, PSA 30.49, QED 0.91
Compound (SMILES): NCc1cc(S(=O)(=O)c2ccc3ccccc3c2)cs1
InChIKey: OBMPUVYMZAASTJ-UHFFFAOYSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P28300
Assay: LOX Enzyme Activity Assay: The following reagents were prepared:Reagents500 mM CHES, pH 9 (with NaOH), filtered (MW=207.29)20.7 g in 200 ml in dH2O10% Pluronic F-127 (store at 4° C.)1 g in 10 ml in dH2O10 % BSA (store at 4° C.)−2.5 g in 25 ml dH2O1 M MgCl2.6H2O (MW=203)5.1 g in 25 ml dH2O5 M Urea (MW=60.06)60 g in 200 ml dH2O5 M NaCl (MW=58.44)14.6 g in 50 ml dH2O8.5 M Cadaverine Dihydrochloride (MW=175.10): Sigma, Cat No: C85611.49 g in 1 ml dH2O10 mM Na3VO4, pH 10 (with HCl), boil to activate (MW=183.91): Sigma, Cat No: S65080.1839 g in 10 ml dH2O20 mM Amplex Red (MW=257.25): Invitrogen, Cat No: A12222.5 mg in 1 ml DMSO (aliquot into 40 μl and store at −20° C.)1000 U/ml HRP in dH2O (store at 4° C.): Sigma, Cat No: P2088H2O2 (store at 4° C.): Sigma, Cat No: H1009DMSOLOX Assay Buffer: Volume (μl) Reagent 1 × plate Final Concn 500 mM CHES, pH 9 5000 100 mM 10% Pluronic F-127 125 0.05% 10% BSA 1250 0.5% 1M MgCl2 25  1 mM 5M Urea 5000 1M 5M NaCl 500 100 mM dH2O 13100 — Total Volume 25 000 —Inhibitors (Test Compounds):10 mM stock diluted to 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001, and 0.0003 mM in drug plate, resulting in a concentration of 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, and 0.003 uM in the assay.LOX enzyme:LOX enzyme was obtained from pig skin by the method of Shackleton et al 1990.Assay Plates:Black, flat bottom 96 well platesProcedure:1. Dilute LOX enzyme in Assay Buffer (˜4 ml for one plate, 8 ml for two plates) (dilution dependent on batch activity)2. Add 0.5 μl test compound serial dilutions, in duplicate3. Add 0.5 μl serial dilutions of positive control, BAPN, down column 11 (no duplication)4. Add following controls: 0.5 μl DMSO (100% activity control)5. Cover plate and incubate for 20 min at room temperature on a plate shaker6. Prepare Start Mix: Volume Reagent 1 × plate 2 × plate Final Concn Assay Buffer 2 ml 3 ml — 8.5M Cadaverine 23 μl 34.5 μl 97.8 mM 20 mM Amplex Red 10 μl 15 μl 100 μM 1000 U/ml HRP 10 μl 15 μl 5 U/ml7. Add 10 μl Start Mix to No HRP control wells8. Add HRP to the Start Mix. Add 10 ul to all wells EXCEPT No HRP control wells9. Incubate for 45 min at room temp on a plate shaker, protected from light10. Measure fluorescence using a plate reader: Excitation wavelength: 545 nm Emission wavelength: 585 nm HRP Counter Assay Protocol1. Dilute 5 μl H2O2 in 640 μl dH2O. Add 1 μl diluted H2O2 to 10 ml Assay Buffer. Vortex2. Add 40 μl H2O2+Assay Buffer into every well on the counter assay plate EXCEPT no H2O2 control wells (add 40 μl Assay Buffer only)3. Add 0.5 μl test compound serial dilutions, in duplicate4. Add 0.5 μl serial dilutions of positive control, Na3VO4, down column 11 (no duplication)5. Add following controls: 0.5 μl DMSO (100% activity control) 1 μl diluted H2O2 (blow out control)6. Incubate for 20 min at room temp on a plate shaker.
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 303.41, ALogP 3.19, HBA 4, HBD 1, PSA 60.16, QED 0.81
Compound (SMILES): Nc1ncnc2c3c(n(-c4ccc(CC(=O)Nc5ccc(Cl)c(C(F)(F)F)c5)cc4)c12)COC3
InChIKey: PULMVLAIWCQJMR-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Displacement of kinase tracer 236 from recombinant human His-tagged KDR cytoplasmic domain (789 to 1356 residues) expressed in baculovirus-infected insect cells measured after 5 hrs by TR-FRET based LanthaScreen assay
Measurement: IC50 > 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 487.87, ALogP 4.89, HBA 6, HBD 2, PSA 95.06, QED 0.43
Compound (SMILES): CC1=CC[C@@]2(C=C1)[C@@H](C(=O)O)CC[C@H]2C1CCCCC1
InChIKey: MJIQEQHXZPYDAR-LZLYRXPVSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of N-terminal MKHQHQHQHQHQHQQPL-tagged 11beta-HSD1 C272S mutant (unknown origin) expressed in Escherichia coli BL21 (DE3) using cortisol as substrate measured for 1 hr in presence of NADPH by fluorescence assay
Measurement: Ki = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 274.4, ALogP 4.57, HBA 1, HBD 1, PSA 37.3, QED 0.8
Compound (SMILES): Cc1ccccc1[Te]CC(O)COc1ccc(S(N)(=O)=O)cc1
InChIKey: LUBRMGCZSLCRGL-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 0.64 nM (pChEMBL 9.1899995803833)
Descriptors: MW 449
Compound (SMILES): COc1ccc(C2=NN(C(C)C)C(=O)[C@@H]3CC=CC[C@H]23)cc1C#CC(=O)NCc1ccccc1
InChIKey: CNKULZYKNGMIIR-BJKOFHAPSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4B catalytic domain using cAMP as substrate incubated for 20 mins by PDELight HTS cAMP phosphodiesterase Kit based luminometry
Measurement: Ki = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 455.56, ALogP 3.9, HBA 4, HBD 1, PSA 71, QED 0.55
Compound (SMILES): O=C1CCC(N2Cc3c(CCCCCNC(=O)c4ccc(NC(=O)[C@@H]5NC6(CCCCC6)[C@@]6(C(=O)Nc7cc(Cl)ccc76)[C@H]5c5cccc(Cl)c5F)cc4)cccc3C2=O)C(=O)N1
InChIKey: RRSNDVCODIMOFX-MPKOGUQCSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to cereblon in human RV4:11/IRMI-2 cells harboring p53 hotspot mutation Y236H/R249G assessed as cell growth inhibition measured after 4 days
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 893.84, ALogP 7.32, HBA 7, HBD 5, PSA 165.81, QED 0.08
Compound (SMILES): O=C(Cc1ccc(Br)cc1)Cn1ccnn1
InChIKey: KGDFBUJUQIOHPF-UHFFFAOYSA-N
Target: Heme oxygenase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23711
Assay: Inhibition of Sprague-Dawley rat brain microsome HO-2 preincubated for 10 mins followed by beta-NADPH addition and measured after 15 mins by gas chromatography
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 280.12, ALogP 1.85, HBA 4, HBD 0, PSA 47.78, QED 0.86
Compound (SMILES): Clc1ccc(CNCC[C@@H]2C[C@H]2c2nc3cc(Cl)ccc3[nH]2)cc1
InChIKey: SQHUIYYAANWTCK-CZUORRHYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Displacement of [3H]histamine from human recombinant histamine H4 receptor expressed in CHO cell membranes after 30 mins by liquid scintillation analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 360.29, ALogP 5.15, HBA 2, HBD 2, PSA 40.71, QED 0.6
Compound (SMILES): CC(C)[C@H](NC(=O)Cn1cccc(O)c1=O)C(=O)OCc1ccccc1
InChIKey: HUSJMVGDLIDROU-KRWDZBQOSA-N
Target: Endoplasmic reticulum aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P179
Assay: Inhibition of human recombinant ERAP2 expressed in baculovirus infected Sf9 cells using omniMMP fluorogenic substrate incubated for 5 to 10 mins by fluorescence spectrophotometry analysis
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 358.39, ALogP 1.44, HBA 6, HBD 2, PSA 97.63, QED 0.73
Compound (SMILES): COc1ccc(CCNc2c(-c3nc(C)n4ccccc34)nc3ccccn23)cc1OC
InChIKey: PODJVYDYKCHELD-UHFFFAOYSA-N
Target: Transcription intermediary factor 1-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15164
Assay: Inhibition of recombinant TRIM24 (unknown origin) using biotinylated H3 peptide (H3K9me3K18ac) by AlphaScreen assay
Measurement: IC50 = 9444 nM (pChEMBL 5.03000020980835)
Descriptors: MW 427.51, ALogP 4.63, HBA 7, HBD 1, PSA 65.09, QED 0.41
Compound (SMILES): OC[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC(C4CCC4)C4CCC4)ncnc31)[C@H](O)[C@@H]2O
InChIKey: SVXHSHXTKYMYNV-UZXPACTOSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Binding affinity to 5HT2B receptor (unknown origin) assessed as inhibition constant
Measurement: Ki = 186.21 nM (pChEMBL 6.730000019073486)
Descriptors: MW 399.5, ALogP 1.48, HBA 8, HBD 4, PSA 116.32, QED 0.58